Full text data of LYN
LYN
(JTK8)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Tyrosine-protein kinase Lyn; 2.7.10.2 (Lck/Yes-related novel protein tyrosine kinase; V-yes-1 Yamaguchi sarcoma viral related oncogene homolog; p53Lyn; p56Lyn)
Tyrosine-protein kinase Lyn; 2.7.10.2 (Lck/Yes-related novel protein tyrosine kinase; V-yes-1 Yamaguchi sarcoma viral related oncogene homolog; p53Lyn; p56Lyn)
UniProt
P07948
ID LYN_HUMAN Reviewed; 512 AA.
AC P07948; A0AVQ5;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 177.
DE RecName: Full=Tyrosine-protein kinase Lyn;
DE EC=2.7.10.2;
DE AltName: Full=Lck/Yes-related novel protein tyrosine kinase;
DE AltName: Full=V-yes-1 Yamaguchi sarcoma viral related oncogene homolog;
DE AltName: Full=p53Lyn;
DE AltName: Full=p56Lyn;
GN Name=LYN; Synonyms=JTK8;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RX PubMed=3561390;
RA Yamanashi Y., Fukushige S., Semba K., Sukegawa J., Miyajima N.,
RA Matsubara K., Yamamoto T., Toyoshima K.;
RT "The yes-related cellular gene lyn encodes a possible tyrosine kinase
RT similar to p56lck.";
RL Mol. Cell. Biol. 7:237-243(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND ALTERNATIVE SPLICING.
RX PubMed=8125304; DOI=10.1016/0378-1119(94)90811-7;
RA Rider L.G., Raben N., Miller L., Jelsema C.;
RT "The cDNAs encoding two forms of the LYN protein tyrosine kinase are
RT expressed in rat mast cells and human myeloid cells.";
RL Gene 138:219-222(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 369-424.
RX PubMed=2247464; DOI=10.1073/pnas.87.22.8913;
RA Partanen J., Maekelae T.P., Alitalo R., Lehvaeslaiho H., Alitalo K.;
RT "Putative tyrosine kinases expressed in K-562 human leukemia cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:8913-8917(1990).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 369-424.
RX PubMed=1510669; DOI=10.1016/S0006-291X(05)81562-1;
RA Bielke W., Ziemiecki A., Kappos L., Miescher G.C.;
RT "Expression of the B cell-associated tyrosine kinase gene Lyn in
RT primary neuroblastoma tumours and its modulation during the
RT differentiation of neuroblastoma cell lines.";
RL Biochem. Biophys. Res. Commun. 186:1403-1409(1992).
RN [6]
RP FUNCTION IN CD19 PHOSPHORYLATION, AND INTERACTION WITH CD19.
RX PubMed=7687428; DOI=10.1006/bbrc.1993.1807;
RA Roifman C.M., Ke S.;
RT "CD19 is a substrate of the antigen receptor-associated protein
RT tyrosine kinase in human B cells.";
RL Biochem. Biophys. Res. Commun. 194:222-225(1993).
RN [7]
RP CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, AND INTERACTION WITH HCLS1.
RX PubMed=7682714; DOI=10.1073/pnas.90.8.3631;
RA Yamanashi Y., Okada M., Semba T., Yamori T., Umemori H., Tsunasawa S.,
RA Toyoshima K., Kitamura D., Watanabe T., Yamamoto T.;
RT "Identification of HS1 protein as a major substrate of protein-
RT tyrosine kinase(s) upon B-cell antigen receptor-mediated signaling.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:3631-3635(1993).
RN [8]
RP INTERACTION WITH FCGR1A, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, AND
RP PHOSPHORYLATION.
RX PubMed=8064233; DOI=10.1084/jem.180.3.1165;
RA Wang A.V., Scholl P.R., Geha R.S.;
RT "Physical and functional association of the high affinity
RT immunoglobulin G receptor (Fc gamma RI) with the kinases Hck and
RT Lyn.";
RL J. Exp. Med. 180:1165-1170(1994).
RN [9]
RP PHOSPHORYLATION AT TYR-397 AND TYR-508, AND ENZYME REGULATION.
RX PubMed=7935444;
RA Hata A., Sabe H., Kurosaki T., Takata M., Hanafusa H.;
RT "Functional analysis of Csk in signal transduction through the B-cell
RT antigen receptor.";
RL Mol. Cell. Biol. 14:7306-7313(1994).
RN [10]
RP INTERACTION WITH EPSTEIN-BARR VIRUS LMP2A.
RX PubMed=7895172; DOI=10.1016/S1074-7613(95)80040-9;
RA Miller C.L., Burkhardt A.L., Lee J.H., Stealey B., Longnecker R.,
RA Bolen J.B., Kieff E.;
RT "Integral membrane protein 2 of Epstein-Barr virus regulates
RT reactivation from latency through dominant negative effects on
RT protein-tyrosine kinases.";
RL Immunity 2:155-166(1995).
RN [11]
RP PHOSPHORYLATION AT TYR-508 BY MATK.
RC TISSUE=Platelet;
RX PubMed=9171348; DOI=10.1093/emboj/16.9.2342;
RA Hirao A., Hamaguchi I., Suda T., Yamaguchi N.;
RT "Translocation of the Csk homologous kinase (Chk/Hyl) controls
RT activity of CD36-anchored Lyn tyrosine kinase in thrombin-stimulated
RT platelets.";
RL EMBO J. 16:2342-2351(1997).
RN [12]
RP INTERACTION WITH FCGR2B.
RX PubMed=9232445; DOI=10.1016/S0165-2478(97)00055-2;
RA Sarmay G., Koncz G., Pecht I., Gergely J.;
RT "Fc gamma receptor type IIb induced recruitment of inositol and
RT protein phosphatases to the signal transductory complex of human B-
RT cell.";
RL Immunol. Lett. 57:159-164(1997).
RN [13]
RP INTERACTION WITH KIT, AND PHOSPHORYLATION.
RX PubMed=9341198; DOI=10.1074/jbc.272.43.27450;
RA Linnekin D., DeBerry C.S., Mou S.;
RT "Lyn associates with the juxtamembrane region of c-Kit and is
RT activated by stem cell factor in hematopoietic cell lines and normal
RT progenitor cells.";
RL J. Biol. Chem. 272:27450-27455(1997).
RN [14]
RP FUNCTION IN DNA DAMAGE RESPONSE; APOPTOSIS AND PHOSPHORYLATION OF
RP PTPN6/SHPTP1, AND INTERACTION WITH PTPN6/SHPTP1.
RX PubMed=10574931; DOI=10.1074/jbc.274.49.34663;
RA Yoshida K., Kharbanda S., Kufe D.;
RT "Functional interaction between SHPTP1 and the Lyn tyrosine kinase in
RT the apoptotic response to DNA damage.";
RL J. Biol. Chem. 274:34663-34668(1999).
RN [15]
RP INTERACTION WITH CBLC.
RX PubMed=10362357; DOI=10.1038/sj.onc.1202753;
RA Keane M.M., Ettenberg S.A., Nau M.M., Banerjee P., Cuello M.,
RA Penninger J., Lipkowitz S.;
RT "cbl-3: a new mammalian cbl family protein.";
RL Oncogene 18:3365-3375(1999).
RN [16]
RP FUNCTION IN CD79A PHOSPHORYLATION, AND INTERACTION WITH CD79A.
RX PubMed=10748115; DOI=10.1074/jbc.M909044199;
RA Gaul B.S., Harrison M.L., Geahlen R.L., Burton R.A., Post C.B.;
RT "Substrate recognition by the Lyn protein-tyrosine kinase. NMR
RT structure of the immunoreceptor tyrosine-based activation motif
RT signaling region of the B cell antigen receptor.";
RL J. Biol. Chem. 275:16174-16182(2000).
RN [17]
RP FUNCTION IN REGULATION OF MAST CELL PROLIFERATION, AND MUTAGENESIS OF
RP LYS-275.
RX PubMed=11435302; DOI=10.1182/blood.V98.2.343;
RA O'Laughlin-Bunner B., Radosevic N., Taylor M.L., Shivakrupa R.,
RA DeBerry C., Metcalfe D.D., Zhou M., Lowell C., Linnekin D.;
RT "Lyn is required for normal stem cell factor-induced proliferation and
RT chemotaxis of primary hematopoietic cells.";
RL Blood 98:343-350(2001).
RN [18]
RP INTERACTION WITH PDE4A.
RC TISSUE=Brain;
RX PubMed=11306681;
RA Rena G., Begg F., Ross A., MacKenzie C., McPhee I., Campbell L.,
RA Huston E., Sullivan M., Houslay M.D.;
RT "Molecular cloning, genomic positioning, promoter identification, and
RT characterization of the novel cyclic AMP-specific phosphodiesterase
RT PDE4A10.";
RL Mol. Pharmacol. 59:996-1011(2001).
RN [19]
RP FUNCTION.
RX PubMed=10891478; DOI=10.1128/MCB.20.15.5370-5380.2000;
RA Yoshida K., Weichselbaum R., Kharbanda S., Kufe D.;
RT "Role for Lyn tyrosine kinase as a regulator of stress-activated
RT protein kinase activity in response to DNA damage.";
RL Mol. Cell. Biol. 20:5370-5380(2000).
RN [20]
RP FUNCTION IN DNA DAMAGE RESPONSE; APOPTOSIS AND PHOSPHORYLATION OF
RP PPP1R15A, INTERACTION WITH PPP1R15A, CATALYTIC ACTIVITY, AND
RP MUTAGENESIS OF LYS-275.
RX PubMed=11517336; DOI=10.1073/pnas.191130798;
RA Grishin A.V., Azhipa O., Semenov I., Corey S.J.;
RT "Interaction between growth arrest-DNA damage protein 34 and Src
RT kinase Lyn negatively regulates genotoxic apoptosis.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:10172-10177(2001).
RN [21]
RP FUNCTION IN PHOSPHORYLATION OF KIT AND DOK1, CATALYTIC ACTIVITY, AND
RP INTERACTION WITH KIT.
RX PubMed=11825908; DOI=10.1074/jbc.M200277200;
RA Liang X., Wisniewski D., Strife A., Shivakrupa R., Clarkson B.,
RA Resh M.D.;
RT "Phosphatidylinositol 3-kinase and Src family kinases are required for
RT phosphorylation and membrane recruitment of Dok-1 in c-Kit
RT signaling.";
RL J. Biol. Chem. 277:13732-13738(2002).
RN [22]
RP INTERACTION WITH MUC1.
RX PubMed=12750561;
RA Li Y., Chen W., Ren J., Yu W.H., Li Q., Yoshida K., Kufe D.;
RT "DF3/MUC1 signaling in multiple myeloma cells is regulated by
RT interleukin-7.";
RL Cancer Biol. Ther. 2:187-193(2003).
RN [23]
RP FUNCTION IN THPO-MEDIATED CELL PROLIFERATION.
RX PubMed=14726379; DOI=10.1182/blood-2003-10-3566;
RA Lannutti B.J., Drachman J.G.;
RT "Lyn tyrosine kinase regulates thrombopoietin-induced proliferation of
RT hematopoietic cell lines and primary megakaryocytic progenitors.";
RL Blood 103:3736-3743(2004).
RN [24]
RP SUBCELLULAR LOCATION, DOMAIN, AND MUTAGENESIS OF LYS-275; ASP-346;
RP GLU-353; ASP-498 AND ASP-499.
RX PubMed=15173188; DOI=10.1083/jcb.200403011;
RA Kasahara K., Nakayama Y., Ikeda K., Fukushima Y., Matsuda D.,
RA Horimoto S., Yamaguchi N.;
RT "Trafficking of Lyn through the Golgi caveolin involves the charged
RT residues on alphaE and alphaI helices in the kinase domain.";
RL J. Cell Biol. 165:641-652(2004).
RN [25]
RP REVIEW ON ROLE IN KIT SIGNALING.
RX PubMed=16129412; DOI=10.1016/j.bbrc.2005.08.055;
RA Roskoski R. Jr.;
RT "Signaling by Kit protein-tyrosine kinase--the stem cell factor
RT receptor.";
RL Biochem. Biophys. Res. Commun. 337:1-13(2005).
RN [26]
RP FUNCTION IN PHOSPHORYLATION OF HCLS1.
RX PubMed=15795233; DOI=10.1074/jbc.M412634200;
RA Brunati A.M., Deana R., Folda A., Massimino M.L., Marin O., Ledro S.,
RA Pinna L.A., Donella-Deana A.;
RT "Thrombin-induced tyrosine phosphorylation of HS1 in human platelets
RT is sequentially catalyzed by Syk and Lyn tyrosine kinases and
RT associated with the cellular migration of the protein.";
RL J. Biol. Chem. 280:21029-21035(2005).
RN [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-508, AND MASS
RP SPECTROMETRY.
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer
RT cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [28]
RP FUNCTION.
RX PubMed=16467205; DOI=10.1182/blood-2005-08-3343;
RA Nakata Y., Tomkowicz B., Gewirtz A.M., Ptasznik A.;
RT "Integrin inhibition through Lyn-dependent cross talk from CXCR4
RT chemokine receptors in normal human CD34+ marrow cells.";
RL Blood 107:4234-4239(2006).
RN [29]
RP INTERACTION WITH ABL1.
RX PubMed=16912036; DOI=10.1074/jbc.M605902200;
RA Meyn M.A. III, Wilson M.B., Abdi F.A., Fahey N., Schiavone A.P.,
RA Wu J., Hochrein J.M., Engen J.R., Smithgall T.E.;
RT "Src family kinases phosphorylate the Bcr-Abl SH3-SH2 region and
RT modulate Bcr-Abl transforming activity.";
RL J. Biol. Chem. 281:30907-30916(2006).
RN [30]
RP INTERACTION WITH PAG1, MUTAGENESIS OF TYR-397 AND TYR-508, ENZYME
RP REGULATION, AND UBIQUITINATION.
RX PubMed=16920712; DOI=10.1074/jbc.M602637200;
RA Ingley E., Schneider J.R., Payne C.J., McCarthy D.J., Harder K.W.,
RA Hibbs M.L., Klinken S.P.;
RT "Csk-binding protein mediates sequential enzymatic down-regulation and
RT degradation of Lyn in erythropoietin-stimulated cells.";
RL J. Biol. Chem. 281:31920-31929(2006).
RN [31]
RP INTERACTION WITH TGFB1I1.
RX PubMed=17233630; DOI=10.1042/BJ20061618;
RA Rathore V.B., Okada M., Newman P.J., Newman D.K.;
RT "Paxillin family members function as Csk-binding proteins that
RT regulate Lyn activity in human and murine platelets.";
RL Biochem. J. 403:275-281(2007).
RN [32]
RP FUNCTION IN PHOSPHORYLATION OF LPXN, AND INTERACTION WITH LPXN.
RX PubMed=17640867; DOI=10.1074/jbc.M704625200;
RA Chew V., Lam K.P.;
RT "Leupaxin negatively regulates B cell receptor signaling.";
RL J. Biol. Chem. 282:27181-27191(2007).
RN [33]
RP INTERACTION WITH TOM1L1, AND FUNCTION IN TOM1L1 PHOSPHORYLATION.
RX PubMed=17977829; DOI=10.1074/jbc.M705168200;
RA Zhang J., Suzuki K., Hitomi T., Siraganian R.P.;
RT "TOM1L1 is a Lyn substrate involved in FcepsilonRI signaling in mast
RT cells.";
RL J. Biol. Chem. 282:37669-37677(2007).
RN [34]
RP FUNCTION IN CELL PROLIFERATION AND SURVIVAL, PHOSPHORYLATION,
RP SUBCELLULAR LOCATION, AND ROLE IN DISEASE.
RX PubMed=18056483; DOI=10.1182/blood-2007-04-082099;
RA Dos Santos C., Demur C., Bardet V., Prade-Houdellier N., Payrastre B.,
RA Recher C.;
RT "A critical role for Lyn in acute myeloid leukemia.";
RL Blood 111:2269-2279(2008).
RN [35]
RP FUNCTION, PHOSPHORYLATION AT TYR-397 AND TYR-508, INTERACTION WITH
RP PAG1 AND STAT3, AND SUBCELLULAR LOCATION.
RX PubMed=18070987; DOI=10.1182/blood-2007-05-090985;
RA Tauzin S., Ding H., Khatib K., Ahmad I., Burdevet D.,
RA van Echten-Deckert G., Lindquist J.A., Schraven B., Din N.U.,
RA Borisch B., Hoessli D.C.;
RT "Oncogenic association of the Cbp/PAG adaptor protein with the Lyn
RT tyrosine kinase in human B-NHL rafts.";
RL Blood 111:2310-2320(2008).
RN [36]
RP INTERACTION WITH CBL AND BCR-ABL, FUNCTION IN PHOSPHORYLATION OF
RP BCR-ABL, AND ROLE IN DISEASE.
RX PubMed=18235045; DOI=10.1182/blood-2007-08-109330;
RA Wu J., Meng F., Lu H., Kong L., Bornmann W., Peng Z., Talpaz M.,
RA Donato N.J.;
RT "Lyn regulates BCR-ABL and Gab2 tyrosine phosphorylation and c-Cbl
RT protein stability in imatinib-resistant chronic myelogenous leukemia
RT cells.";
RL Blood 111:3821-3829(2008).
RN [37]
RP SUBCELLULAR LOCATION, MYRISTOYLATION AT GLY-2, AND MUTAGENESIS OF
RP GLY-2; CYS-3 AND LYS-275.
RX PubMed=18817770; DOI=10.1016/j.yexcr.2008.08.019;
RA Ikeda K., Nakayama Y., Togashi Y., Obata Y., Kuga T., Kasahara K.,
RA Fukumoto Y., Yamaguchi N.;
RT "Nuclear localization of Lyn tyrosine kinase mediated by inhibition of
RT its kinase activity.";
RL Exp. Cell Res. 314:3392-3404(2008).
RN [38]
RP FUNCTION IN ADHESION AND CELL MIGRATION.
RX PubMed=18802065;
RA Malik M., Chen Y.-Y., Kienzle M.F., Tomkowicz B.E., Collman R.G.,
RA Ptasznik A.;
RT "Monocyte migration and LFA-1-mediated attachment to brain
RT microvascular endothelia is regulated by SDF-1 alpha through Lyn
RT kinase.";
RL J. Immunol. 181:4632-4637(2008).
RN [39]
RP PHOSPHORYLATION AT TYR-460, AND ROLE IN DISEASE.
RX PubMed=18577747; DOI=10.1093/jnci/djn188;
RA Wu J., Meng F., Kong L.Y., Peng Z., Ying Y., Bornmann W.G.,
RA Darnay B.G., Lamothe B., Sun H., Talpaz M., Donato N.J.;
RT "Association between imatinib-resistant BCR-ABL mutation-negative
RT leukemia and persistent activation of LYN kinase.";
RL J. Natl. Cancer Inst. 100:926-939(2008).
RN [40]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [41]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-11; SER-13; TYR-473 AND
RP TYR-508, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [42]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [43]
RP INTERACTION WITH FASLG.
RX PubMed=19807924; DOI=10.1186/1471-2172-10-53;
RA Voss M., Lettau M., Janssen O.;
RT "Identification of SH3 domain interaction partners of human FasL
RT (CD178) by phage display screening.";
RL BMC Immunol. 10:53-53(2009).
RN [44]
RP INTERACTION WITH ADAM15.
RX PubMed=19718658; DOI=10.1002/jcb.22317;
RA Kleino I., Ortiz R.M., Yritys M., Huovila A.P., Saksela K.;
RT "Alternative splicing of ADAM15 regulates its interactions with
RT cellular SH3 proteins.";
RL J. Cell. Biochem. 108:877-885(2009).
RN [45]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-11; SER-13; SER-228;
RP TYR-306; TYR-316; TYR-473 AND TYR-508, AND MASS SPECTROMETRY.
RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [46]
RP FUNCTION IN PTK2B/PYK2 PHOSPHORYLATION.
RX PubMed=20028775; DOI=10.1189/jlb.0409227;
RA Collins M., Tremblay M., Chapman N., Curtiss M., Rothman P.B.,
RA Houtman J.C.;
RT "The T cell receptor-mediated phosphorylation of Pyk2 tyrosines 402
RT and 580 occurs via a distinct mechanism than other receptor systems.";
RL J. Leukoc. Biol. 87:691-701(2010).
RN [47]
RP INTERACTION WITH NDFIP1 AND NDFIP2, AND UBIQUITINATION.
RX PubMed=20534535; DOI=10.1073/pnas.0911714107;
RA Mund T., Pelham H.R.;
RT "Regulation of PTEN/Akt and MAP kinase signaling pathways by the
RT ubiquitin ligase activators Ndfip1 and Ndfip2.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:11429-11434(2010).
RN [48]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-13, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [49]
RP INTERACTION WITH SCIMP.
RX PubMed=21930792; DOI=10.1128/MCB.05817-11;
RA Draber P., Vonkova I., Stepanek O., Hrdinka M., Kucova M.,
RA Skopcova T., Otahal P., Angelisova P., Horejsi V., Yeung M., Weiss A.,
RA Brdicka T.;
RT "SCIMP, a transmembrane adapter protein involved in major
RT histocompatibility complex class II signaling.";
RL Mol. Cell. Biol. 31:4550-4562(2011).
RN [50]
RP REVIEW.
RX PubMed=15220000; DOI=10.1016/j.molimm.2004.04.010;
RA Lowell C.A.;
RT "Src-family kinases: rheostats of immune cell signaling.";
RL Mol. Immunol. 41:631-643(2004).
RN [51]
RP REVIEW ON ROLE IN B CELLS.
RX PubMed=15489917; DOI=10.1038/sj.onc.1208075;
RA Gauld S.B., Cambier J.C.;
RT "Src-family kinases in B-cell development and signaling.";
RL Oncogene 23:8001-8006(2004).
RN [52]
RP REVIEW ON ROLE IN B CELLS.
RX PubMed=15664155; DOI=10.1016/j.immuni.2004.12.004;
RA Xu Y., Harder K.W., Huntington N.D., Hibbs M.L., Tarlinton D.M.;
RT "Lyn tyrosine kinase: accentuating the positive and the negative.";
RL Immunity 22:9-18(2005).
RN [53]
RP REVIEW ON ROLE IN GROWTH FACTOR SIGNALING.
RX PubMed=16801133; DOI=10.1080/08977190600581327;
RA Hibbs M.L., Harder K.W.;
RT "The duplicitous nature of the Lyn tyrosine kinase in growth factor
RT signaling.";
RL Growth Factors 24:137-149(2006).
RN [54]
RP REVIEW ON ROLE IN MAST CELLS.
RX PubMed=18772004; DOI=10.1016/S0065-2776(08)00403-3;
RA Rivera J., Fierro N.A., Olivera A., Suzuki R.;
RT "New insights on mast cell activation via the high affinity receptor
RT for IgE.";
RL Adv. Immunol. 98:85-120(2008).
RN [55]
RP REVIEW ON ROLE IN MYELOID CELL FUNCTION AND SIGNALING.
RX PubMed=19290919; DOI=10.1111/j.1600-065X.2008.00758.x;
RA Scapini P., Pereira S., Zhang H., Lowell C.A.;
RT "Multiple roles of Lyn kinase in myeloid cell signaling and
RT function.";
RL Immunol. Rev. 228:23-40(2009).
RN [56]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-11 AND SER-13, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [57]
RP STRUCTURE BY NMR OF 61-123 IN COMPLEX WITH SAIMIRIINE HERPESVIRUS 2
RP TYROSINE KINASE INTERACTING PROTEIN.
RX PubMed=11955060; DOI=10.1021/bi015986j;
RA Schweimer K., Hoffmann S., Bauer F., Friedrich U., Kardinal C.,
RA Feller S.M., Biesinger B., Sticht H.;
RT "Structural investigation of the binding of a herpesviral protein to
RT the SH3 domain of tyrosine kinase Lck.";
RL Biochemistry 41:5120-5130(2002).
RN [58]
RP STRUCTURE BY NMR OF 61-122, AND INTERACTION WITH HERPESVIRUS TYROSINE
RP KINASE INTERACTING PROTEIN.
RX PubMed=16155203; DOI=10.1110/ps.051563605;
RA Bauer F., Schweimer K., Meiselbach H., Hoffmann S., Rosch P.,
RA Sticht H.;
RT "Structural characterization of Lyn-SH3 domain in complex with a
RT herpesviral protein reveals an extended recognition motif that
RT enhances binding affinity.";
RL Protein Sci. 14:2487-2498(2005).
RN [59]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 233-512 IN COMPLEX WITH
RP STAUROSPORINE.
RX PubMed=19857964; DOI=10.1016/j.bmcl.2009.10.038;
RA Miyano N., Kinoshita T., Nakai R., Kirii Y., Yokota K., Tada T.;
RT "Structural basis for the inhibitor recognition of human Lyn kinase
RT domain.";
RL Bioorg. Med. Chem. Lett. 19:6557-6560(2009).
RN [60]
RP VARIANT [LARGE SCALE ANALYSIS] TYR-385.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C.,
RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S.,
RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S.,
RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E.,
RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J.,
RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K.,
RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T.,
RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P.,
RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E.,
RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E.,
RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T.,
RA Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Non-receptor tyrosine-protein kinase that transmits
CC signals from cell surface receptors and plays an important role in
CC the regulation of innate and adaptive immune responses,
CC hematopoiesis, responses to growth factors and cytokines, integrin
CC signaling, but also responses to DNA damage and genotoxic agents.
CC Functions primarily as negative regulator, but can also function
CC as activator, depending on the context. Required for the
CC initiation of the B-cell response, but also for its down-
CC regulation and termination. Plays an important role in the
CC regulation of B-cell differentiation, proliferation, survival and
CC apoptosis, and is important for immune self-tolerance. Acts
CC downstream of several immune receptors, including the B-cell
CC receptor, CD79A, CD79B, CD5, CD19, CD22, FCER1, FCGR2, FCGR1A,
CC TLR2 and TLR4. Plays a role in the inflammatory response to
CC bacterial lipopolysaccharide. Mediates the responses to cytokines
CC and growth factors in hematopoietic progenitors, platelets,
CC erythrocytes, and in mature myeloid cells, such as dendritic
CC cells, neutrophils and eosinophils. Acts downstream of EPOR, KIT,
CC MPL, the chemokine receptor CXCR4, as well as the receptors for
CC IL3, IL5 and CSF2. Plays an important role in integrin signaling.
CC Regulates cell proliferation, survival, differentiation,
CC migration, adhesion, degranulation, and cytokine release. Down-
CC regulates signaling pathways by phosphorylation of immunoreceptor
CC tyrosine-based inhibitory motifs (ITIM), that then serve as
CC binding sites for phosphatases, such as PTPN6/SHP-1, PTPN11/SHP-2
CC and INPP5D/SHIP-1, that modulate signaling by dephosphorylation of
CC kinases and their substrates. Phosphorylates LIME1 in response to
CC CD22 activation. Phosphorylates BTK, CBL, CD5, CD19, CD72, CD79A,
CC CD79B, CSF2RB, DOK1, HCLS1, LILRB3/PIR-B, MS4A2/FCER1B,
CC PTK2B/PYK2, SYK and TEC. Promotes phosphorylation of SIRPA,
CC PTPN6/SHP-1, PTPN11/SHP-2 and INPP5D/SHIP-1. Mediates
CC phosphorylation of the BCR-ABL fusion protein. Required for rapid
CC phosphorylation of FER in response to FCER1 activation. Mediates
CC KIT phosphorylation. Acts as an effector of EPOR (erythropoietin
CC receptor) in controlling KIT expression and may play a role in
CC erythroid differentiation during the switch between proliferation
CC and maturation. Depending on the context, activates or inhibits
CC several signaling cascades. Regulates phosphatidylinositol 3-
CC kinase activity and AKT1 activation. Regulates activation of the
CC MAP kinase signaling cascade, including activation of MAP2K1/MEK1,
CC MAPK1/ERK2, MAPK3/ERK1, MAPK8/JNK1 and MAPK9/JNK2. Mediates
CC activation of STAT5A and/or STAT5B. Phosphorylates LPXN on 'Tyr-
CC 72'.
CC -!- CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a
CC [protein]-L-tyrosine phosphate.
CC -!- ENZYME REGULATION: Subject to autoinhibition, mediated by
CC intramolecular interactions between the SH2 domain and the C-
CC terminal phosphotyrosine. Phosphorylation at Tyr-397 is required
CC for optimal activity. Phosphorylated by CSK at Tyr-508;
CC phosphorylation at Tyr-508 inhibits kinase activity. Kinase
CC activity is modulated by dephosphorylation by PTPRC/CD45.
CC Inhibited by Dasatinib, PP2, and SU6656.
CC -!- SUBUNIT: Interacts with TEC. Interacts (via SH2 domain) with FLT3
CC (tyrosine phosphorylated). Interacts with LIME1 and with CD79A
CC upon activation of the B-cell antigen receptor. Interacts with the
CC B-cell receptor complex. Interacts with phosphorylated THEMIS2.
CC Interacts with EPOR. Interacts with MS4A2/FCER1B. Interaction (via
CC the SH2 and SH3 domains) with MUC1 is stimulated by IL7 and the
CC subsequent phosphorylation increases the binding between MUC1 and
CC CTNNB1/beta-catenin. Interacts with ADAM15. Interacts with NDFIP2
CC and more weakly with NDFIP1. Interacts with FASLG. Interacts with
CC KIT. Interacts with HCLS1. Interacts with FCGR2B. Interacts with
CC FCGR1A; the interaction may be indirect. Interacts with CD19,
CC CD22, CD79A and CD79B. Interacts (via SH3 domain) with CBLC,
CC PPP1R15A and PDE4A. Interacts with TGFB1I1. Interacts (via SH3
CC domain) with PIK3R1, the regulatory subunit of
CC phosphatidylinositol 3-kinase; this interaction enhances
CC phosphatidylinositol 3-kinase activity. Interacts with CSF2RB, the
CC common subunit of the IL3, IL5 and CSF2 receptors. Interacts with
CC PAG1; identified in a complex with PAG1 and STAT3. Interacts with
CC ABL1. Interacts with PTPN6/SHP-1. Interacts (via SH3 domain) with
CC SCIMP (via proline-rich region). Interacts with LPXN (via LD motif
CC 3) and the interaction is induced upon B-cell antigen receptor
CC (BCR) activation. Interacts (via SH3-domain) with ANKRD54 (via
CC ankyrin repeat region) in an activation-independent status of LYN.
CC Forms a multiprotein complex with ANKRD54 and HCLS1. Interacts
CC with Epstein-Barr virus LMP2A. Interacts with Herpes virus saimiri
CC tyrosine kinase interacting protein (Tip).
CC -!- INTERACTION:
CC O92972:- (xeno); NbExp=2; IntAct=EBI-79452, EBI-710506;
CC P22575:- (xeno); NbExp=3; IntAct=EBI-79452, EBI-866709;
CC P27958:- (xeno); NbExp=5; IntAct=EBI-79452, EBI-706378;
CC Q9WMX2:- (xeno); NbExp=3; IntAct=EBI-79452, EBI-710918;
CC Q8R5G7:Arap3 (xeno); NbExp=2; IntAct=EBI-79452, EBI-621463;
CC P20273:CD22; NbExp=2; IntAct=EBI-79452, EBI-78277;
CC P25063:CD24; NbExp=6; IntAct=EBI-79452, EBI-6267018;
CC P11049:CD37; NbExp=5; IntAct=EBI-79452, EBI-6139068;
CC P46527:CDKN1B; NbExp=2; IntAct=EBI-79452, EBI-519280;
CC P00533:EGFR; NbExp=3; IntAct=EBI-79452, EBI-297353;
CC Q9HCN6:GP6; NbExp=2; IntAct=EBI-79452, EBI-515278;
CC P05556:ITGB1; NbExp=4; IntAct=EBI-79452, EBI-703066;
CC P33993:MCM7; NbExp=5; IntAct=EBI-6895930, EBI-355924;
CC -!- SUBCELLULAR LOCATION: Cell membrane. Nucleus. Cytoplasm.
CC Cytoplasm, perinuclear region. Golgi apparatus. Note=Accumulates
CC in the nucleus by inhibition of CRM1-mediated nuclear export.
CC Nuclear accumulation is increased by inhibition of its kinase
CC activity. The trafficking from the Golgi apparatus to the plasma
CC membrane occurs in a kinase domain-dependent but kinase activity
CC independent manner and is mediated by exocytic vesicular
CC transport. Detected on plasma membrane lipid rafts.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=LYN A, p56lyn;
CC IsoId=P07948-1; Sequence=Displayed;
CC Name=2; Synonyms=LYN B, p53lyn;
CC IsoId=P07948-2; Sequence=VSP_005002;
CC -!- TISSUE SPECIFICITY: Detected in monocytes (at protein level).
CC Detected in placenta, and in fetal brain, lung, liver and kidney.
CC Widely expressed in a variety of organs, tissues, and cell types
CC such as epidermoid, hematopoietic, and neuronal cells. Expressed
CC in primary neuroblastoma tumors.
CC -!- DOMAIN: The protein kinase domain plays an important role in its
CC localization in the cell membrane.
CC -!- PTM: Ubiquitinated by CBL, leading to its degradation.
CC Ubiquitination is SH3-dependent.
CC -!- PTM: Autophosphorylated. Phosphorylated on tyrosine residues in
CC response to KIT signaling. Phosphorylation at Tyr-397 is required
CC for optimal activity. Phosphorylation at Tyr-508 inhibits kinase
CC activity. Phosphorylated at Tyr-508 by CSK. Dephosphorylated by
CC PTPRC/CD45. Becomes rapidly phosphorylated upon activation of the
CC B-cell receptor and the immunoglobulin receptor FCGR1A.
CC -!- DISEASE: Note=Constitutively phosphorylated and activated in cells
CC from a number of chronic myelogenous leukemia (CML) and acute
CC myeloid leukemia (AML) patients. Mediates phosphorylation of the
CC BCR-ABL fusion protein. Abnormally elevated expression levels or
CC activation of LYN signaling may play a role in survival and
CC proliferation of some types of cancer cells.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. SRC subfamily.
CC -!- SIMILARITY: Contains 1 protein kinase domain.
CC -!- SIMILARITY: Contains 1 SH2 domain.
CC -!- SIMILARITY: Contains 1 SH3 domain.
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DR EMBL; M16038; AAA59540.1; -; mRNA.
DR EMBL; M79321; AAB50019.1; -; mRNA.
DR EMBL; BC075001; AAH75001.1; -; mRNA.
DR EMBL; BC075002; AAH75002.1; -; mRNA.
DR EMBL; BC126456; AAI26457.1; -; mRNA.
DR EMBL; BC126458; AAI26459.1; -; mRNA.
DR PIR; A26719; TVHULY.
DR RefSeq; NP_001104567.1; NM_001111097.2.
DR RefSeq; NP_002341.1; NM_002350.3.
DR RefSeq; XP_005251289.1; XM_005251232.1.
DR RefSeq; XP_005251290.1; XM_005251233.1.
DR UniGene; Hs.491767; -.
DR UniGene; Hs.545418; -.
DR PDB; 1W1F; NMR; -; A=61-123.
DR PDB; 1WA7; NMR; -; A=61-123.
DR PDB; 3A4O; X-ray; 3.00 A; X=233-512.
DR PDBsum; 1W1F; -.
DR PDBsum; 1WA7; -.
DR PDBsum; 3A4O; -.
DR ProteinModelPortal; P07948; -.
DR SMR; P07948; 64-512.
DR DIP; DIP-1056N; -.
DR IntAct; P07948; 46.
DR MINT; MINT-200655; -.
DR STRING; 9606.ENSP00000376688; -.
DR BindingDB; P07948; -.
DR ChEMBL; CHEMBL2363074; -.
DR GuidetoPHARMACOLOGY; 2060; -.
DR PhosphoSite; P07948; -.
DR DMDM; 125480; -.
DR REPRODUCTION-2DPAGE; P07948; -.
DR PaxDb; P07948; -.
DR PRIDE; P07948; -.
DR DNASU; 4067; -.
DR Ensembl; ENST00000519728; ENSP00000428924; ENSG00000254087.
DR Ensembl; ENST00000520220; ENSP00000428424; ENSG00000254087.
DR GeneID; 4067; -.
DR KEGG; hsa:4067; -.
DR UCSC; uc003xsk.4; human.
DR CTD; 4067; -.
DR GeneCards; GC08P056792; -.
DR HGNC; HGNC:6735; LYN.
DR HPA; CAB004492; -.
DR HPA; HPA001231; -.
DR MIM; 165120; gene.
DR neXtProt; NX_P07948; -.
DR PharmGKB; PA30498; -.
DR eggNOG; COG0515; -.
DR HOGENOM; HOG000233858; -.
DR HOVERGEN; HBG008761; -.
DR KO; K05854; -.
DR OMA; ISSMIKH; -.
DR PhylomeDB; P07948; -.
DR BRENDA; 2.7.10.2; 2681.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_604; Hemostasis.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; P07948; -.
DR ChiTaRS; LYN; human.
DR EvolutionaryTrace; P07948; -.
DR GeneWiki; LYN; -.
DR GenomeRNAi; 4067; -.
DR NextBio; 15944; -.
DR PMAP-CutDB; P07948; -.
DR PRO; PR:P07948; -.
DR ArrayExpress; P07948; -.
DR Bgee; P07948; -.
DR CleanEx; HS_LYN; -.
DR Genevestigator; P07948; -.
DR GO; GO:0034666; C:alpha2-beta1 integrin complex; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IDA:UniProtKB.
DR GO; GO:0030061; C:mitochondrial crista; IEA:Ensembl.
DR GO; GO:0005758; C:mitochondrial intermembrane space; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0014069; C:postsynaptic density; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0043208; F:glycosphingolipid binding; IEA:Ensembl.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; TAS:Reactome.
DR GO; GO:0004716; F:receptor signaling protein tyrosine kinase activity; TAS:ProtInc.
DR GO; GO:0030262; P:apoptotic nuclear changes; IDA:UniProtKB.
DR GO; GO:0001782; P:B cell homeostasis; ISS:UniProtKB.
DR GO; GO:0050853; P:B cell receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0031668; P:cellular response to extracellular stimulus; IEA:Ensembl.
DR GO; GO:0034605; P:cellular response to heat; IEA:Ensembl.
DR GO; GO:0071300; P:cellular response to retinoic acid; IMP:BHF-UCL.
DR GO; GO:0050663; P:cytokine secretion; IEA:Ensembl.
DR GO; GO:0097028; P:dendritic cell differentiation; ISS:UniProtKB.
DR GO; GO:0030218; P:erythrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0002774; P:Fc receptor mediated inhibitory signaling pathway; ISS:UniProtKB.
DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome.
DR GO; GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome.
DR GO; GO:0002553; P:histamine secretion by mast cell; IEA:Ensembl.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IC:UniProtKB.
DR GO; GO:0060397; P:JAK-STAT cascade involved in growth hormone signaling pathway; TAS:Reactome.
DR GO; GO:0050900; P:leukocyte migration; TAS:Reactome.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0030889; P:negative regulation of B cell proliferation; IEA:Ensembl.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0050777; P:negative regulation of immune response; TAS:UniProtKB.
DR GO; GO:0043407; P:negative regulation of MAP kinase activity; ISS:UniProtKB.
DR GO; GO:0070667; P:negative regulation of mast cell proliferation; ISS:UniProtKB.
DR GO; GO:0002762; P:negative regulation of myeloid leukocyte differentiation; IEA:Ensembl.
DR GO; GO:0034136; P:negative regulation of toll-like receptor 2 signaling pathway; ISS:UniProtKB.
DR GO; GO:0034144; P:negative regulation of toll-like receptor 4 signaling pathway; ISS:UniProtKB.
DR GO; GO:0031175; P:neuron projection development; IEA:Ensembl.
DR GO; GO:0014003; P:oligodendrocyte development; IEA:Ensembl.
DR GO; GO:0030168; P:platelet activation; TAS:Reactome.
DR GO; GO:0002576; P:platelet degranulation; ISS:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; IEA:Ensembl.
DR GO; GO:0051272; P:positive regulation of cellular component movement; IDA:UniProtKB.
DR GO; GO:2000670; P:positive regulation of dendritic cell apoptotic process; ISS:UniProtKB.
DR GO; GO:0060369; P:positive regulation of Fc receptor mediated stimulatory signaling pathway; IEA:Ensembl.
DR GO; GO:0060252; P:positive regulation of glial cell proliferation; IEA:Ensembl.
DR GO; GO:0070668; P:positive regulation of mast cell proliferation; IMP:UniProtKB.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IMP:BHF-UCL.
DR GO; GO:0070447; P:positive regulation of oligodendrocyte progenitor proliferation; IEA:Ensembl.
DR GO; GO:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; IEA:Ensembl.
DR GO; GO:0070304; P:positive regulation of stress-activated protein kinase signaling cascade; IDA:UniProtKB.
DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; ISS:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0002902; P:regulation of B cell apoptotic process; IEA:Ensembl.
DR GO; GO:0050855; P:regulation of B cell receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0033628; P:regulation of cell adhesion mediated by integrin; IMP:UniProtKB.
DR GO; GO:0001817; P:regulation of cytokine production; ISS:UniProtKB.
DR GO; GO:0050707; P:regulation of cytokine secretion; IEA:Ensembl.
DR GO; GO:0045646; P:regulation of erythrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0050727; P:regulation of inflammatory response; IEA:Ensembl.
DR GO; GO:0043304; P:regulation of mast cell degranulation; ISS:UniProtKB.
DR GO; GO:0090025; P:regulation of monocyte chemotaxis; IMP:UniProtKB.
DR GO; GO:0090330; P:regulation of platelet aggregation; ISS:UniProtKB.
DR GO; GO:0051279; P:regulation of release of sequestered calcium ion into cytosol; IEA:Ensembl.
DR GO; GO:0043200; P:response to amino acid stimulus; IEA:Ensembl.
DR GO; GO:0048678; P:response to axon injury; IEA:Ensembl.
DR GO; GO:0009743; P:response to carbohydrate stimulus; IEA:Ensembl.
DR GO; GO:0032868; P:response to insulin stimulus; IEA:Ensembl.
DR GO; GO:0014070; P:response to organic cyclic compound; IEA:Ensembl.
DR GO; GO:0006991; P:response to sterol depletion; IEA:Ensembl.
DR GO; GO:0009636; P:response to toxic substance; IEA:Ensembl.
DR GO; GO:0031295; P:T cell costimulation; TAS:Reactome.
DR GO; GO:0002513; P:tolerance induction to self antigen; ISS:UniProtKB.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR011009; Kinase-like_dom.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR001452; SH3_domain.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR Pfam; PF07714; Pkinase_Tyr; 1.
DR Pfam; PF00017; SH2; 1.
DR Pfam; PF00018; SH3_1; 1.
DR PRINTS; PR00401; SH2DOMAIN.
DR PRINTS; PR00452; SH3DOMAIN.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00252; SH2; 1.
DR SMART; SM00326; SH3; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR PROSITE; PS50001; SH2; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Alternative splicing; ATP-binding;
KW Cell membrane; Complete proteome; Cytoplasm; Golgi apparatus;
KW Host-virus interaction; Immunity; Inflammatory response;
KW Innate immunity; Kinase; Lipoprotein; Membrane; Myristate;
KW Nucleotide-binding; Nucleus; Palmitate; Phosphoprotein; Polymorphism;
KW Proto-oncogene; Reference proteome; SH2 domain; SH3 domain;
KW Transferase; Tyrosine-protein kinase; Ubl conjugation.
FT INIT_MET 1 1 Removed (Probable).
FT CHAIN 2 512 Tyrosine-protein kinase Lyn.
FT /FTId=PRO_0000088129.
FT DOMAIN 63 123 SH3.
FT DOMAIN 129 226 SH2.
FT DOMAIN 247 501 Protein kinase.
FT NP_BIND 253 261 ATP (By similarity).
FT ACT_SITE 367 367 Proton acceptor (By similarity).
FT BINDING 275 275 ATP (By similarity).
FT MOD_RES 6 6 Phosphoserine.
FT MOD_RES 11 11 Phosphoserine.
FT MOD_RES 13 13 Phosphoserine.
FT MOD_RES 30 30 Phosphothreonine.
FT MOD_RES 32 32 Phosphotyrosine.
FT MOD_RES 37 37 Phosphothreonine.
FT MOD_RES 193 193 Phosphotyrosine.
FT MOD_RES 194 194 Phosphotyrosine.
FT MOD_RES 228 228 Phosphoserine.
FT MOD_RES 265 265 Phosphotyrosine.
FT MOD_RES 306 306 Phosphotyrosine.
FT MOD_RES 316 316 Phosphotyrosine.
FT MOD_RES 397 397 Phosphotyrosine; by autocatalysis.
FT MOD_RES 460 460 Phosphotyrosine.
FT MOD_RES 473 473 Phosphotyrosine.
FT MOD_RES 489 489 Phosphothreonine.
FT MOD_RES 502 502 Phosphothreonine.
FT MOD_RES 508 508 Phosphotyrosine; by autocatalysis, CSK
FT and MATK.
FT LIPID 2 2 N-myristoyl glycine (Probable).
FT LIPID 3 3 S-palmitoyl cysteine (Probable).
FT VAR_SEQ 23 43 Missing (in isoform 2).
FT /FTId=VSP_005002.
FT VARIANT 385 385 D -> Y (in a breast pleomorphic lobular
FT carcinoma sample; somatic mutation).
FT /FTId=VAR_041737.
FT MUTAGEN 2 2 G->A: Loss of localization to the cell
FT membrane; when associated with A-3.
FT MUTAGEN 3 3 C->A: Loss of localization to the cell
FT membrane; when associated with A-2.
FT MUTAGEN 275 275 K->A: Loss of activity and no effect on
FT localization to the cell membrane.
FT Abundant localization in the nucleus;
FT when associated with A-2 and A-3.
FT MUTAGEN 275 275 K->L,R: Loss of kinase activity.
FT MUTAGEN 346 346 D->A: Impedes the trafficking from the
FT Golgi apparatus toward the cell membrane;
FT when associated with A-353; A-498 and A-
FT 499.
FT MUTAGEN 353 353 E->A: Impedes the trafficking from the
FT Golgi apparatus toward the cell membrane;
FT when associated with A-346; A-498 and A-
FT 499.
FT MUTAGEN 397 397 Y->F: Strongly reduced kinase activity.
FT MUTAGEN 498 498 D->A: Impedes the trafficking from the
FT Golgi apparatus toward the cell membrane;
FT when associated with A-346; A-353 and A-
FT 499.
FT MUTAGEN 499 499 D->A: Impedes the trafficking from the
FT Golgi apparatus toward the cell membrane;
FT when associated with A-346; A-353 and A-
FT 498.
FT MUTAGEN 508 508 Y->F: Abolishes autoinhibition and
FT thereby increases kinase activity.
FT STRAND 66 72
FT STRAND 78 80
FT STRAND 89 95
FT STRAND 97 104
FT TURN 105 107
FT STRAND 110 114
FT TURN 115 117
FT STRAND 118 120
FT STRAND 259 262
FT STRAND 265 269
FT STRAND 273 275
FT STRAND 284 286
FT TURN 287 289
FT HELIX 290 293
FT TURN 294 297
FT STRAND 306 309
FT STRAND 311 314
FT STRAND 316 319
FT HELIX 327 330
FT HELIX 334 338
FT HELIX 341 360
FT STRAND 372 375
FT STRAND 381 383
FT HELIX 407 409
FT HELIX 412 416
FT HELIX 422 437
FT TURN 449 451
FT HELIX 452 457
FT STRAND 466 468
FT HELIX 470 477
FT TURN 478 480
FT TURN 484 486
FT HELIX 490 502
SQ SEQUENCE 512 AA; 58574 MW; 408D3D461204E378 CRC64;
MGCIKSKGKD SLSDDGVDLK TQPVRNTERT IYVRDPTSNK QQRPVPESQL LPGQRFQTKD
PEEQGDIVVA LYPYDGIHPD DLSFKKGEKM KVLEEHGEWW KAKSLLTKKE GFIPSNYVAK
LNTLETEEWF FKDITRKDAE RQLLAPGNSA GAFLIRESET LKGSFSLSVR DFDPVHGDVI
KHYKIRSLDN GGYYISPRIT FPCISDMIKH YQKQADGLCR RLEKACISPK PQKPWDKDAW
EIPRESIKLV KRLGAGQFGE VWMGYYNNST KVAVKTLKPG TMSVQAFLEE ANLMKTLQHD
KLVRLYAVVT REEPIYIITE YMAKGSLLDF LKSDEGGKVL LPKLIDFSAQ IAEGMAYIER
KNYIHRDLRA ANVLVSESLM CKIADFGLAR VIEDNEYTAR EGAKFPIKWT APEAINFGCF
TIKSDVWSFG ILLYEIVTYG KIPYPGRTNA DVMTALSQGY RMPRVENCPD ELYDIMKMCW
KEKAEERPTF DYLQSVLDDF YTATEGQYQQ QP
//
ID LYN_HUMAN Reviewed; 512 AA.
AC P07948; A0AVQ5;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 177.
DE RecName: Full=Tyrosine-protein kinase Lyn;
DE EC=2.7.10.2;
DE AltName: Full=Lck/Yes-related novel protein tyrosine kinase;
DE AltName: Full=V-yes-1 Yamaguchi sarcoma viral related oncogene homolog;
DE AltName: Full=p53Lyn;
DE AltName: Full=p56Lyn;
GN Name=LYN; Synonyms=JTK8;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RX PubMed=3561390;
RA Yamanashi Y., Fukushige S., Semba K., Sukegawa J., Miyajima N.,
RA Matsubara K., Yamamoto T., Toyoshima K.;
RT "The yes-related cellular gene lyn encodes a possible tyrosine kinase
RT similar to p56lck.";
RL Mol. Cell. Biol. 7:237-243(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND ALTERNATIVE SPLICING.
RX PubMed=8125304; DOI=10.1016/0378-1119(94)90811-7;
RA Rider L.G., Raben N., Miller L., Jelsema C.;
RT "The cDNAs encoding two forms of the LYN protein tyrosine kinase are
RT expressed in rat mast cells and human myeloid cells.";
RL Gene 138:219-222(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 369-424.
RX PubMed=2247464; DOI=10.1073/pnas.87.22.8913;
RA Partanen J., Maekelae T.P., Alitalo R., Lehvaeslaiho H., Alitalo K.;
RT "Putative tyrosine kinases expressed in K-562 human leukemia cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:8913-8917(1990).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 369-424.
RX PubMed=1510669; DOI=10.1016/S0006-291X(05)81562-1;
RA Bielke W., Ziemiecki A., Kappos L., Miescher G.C.;
RT "Expression of the B cell-associated tyrosine kinase gene Lyn in
RT primary neuroblastoma tumours and its modulation during the
RT differentiation of neuroblastoma cell lines.";
RL Biochem. Biophys. Res. Commun. 186:1403-1409(1992).
RN [6]
RP FUNCTION IN CD19 PHOSPHORYLATION, AND INTERACTION WITH CD19.
RX PubMed=7687428; DOI=10.1006/bbrc.1993.1807;
RA Roifman C.M., Ke S.;
RT "CD19 is a substrate of the antigen receptor-associated protein
RT tyrosine kinase in human B cells.";
RL Biochem. Biophys. Res. Commun. 194:222-225(1993).
RN [7]
RP CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, AND INTERACTION WITH HCLS1.
RX PubMed=7682714; DOI=10.1073/pnas.90.8.3631;
RA Yamanashi Y., Okada M., Semba T., Yamori T., Umemori H., Tsunasawa S.,
RA Toyoshima K., Kitamura D., Watanabe T., Yamamoto T.;
RT "Identification of HS1 protein as a major substrate of protein-
RT tyrosine kinase(s) upon B-cell antigen receptor-mediated signaling.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:3631-3635(1993).
RN [8]
RP INTERACTION WITH FCGR1A, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, AND
RP PHOSPHORYLATION.
RX PubMed=8064233; DOI=10.1084/jem.180.3.1165;
RA Wang A.V., Scholl P.R., Geha R.S.;
RT "Physical and functional association of the high affinity
RT immunoglobulin G receptor (Fc gamma RI) with the kinases Hck and
RT Lyn.";
RL J. Exp. Med. 180:1165-1170(1994).
RN [9]
RP PHOSPHORYLATION AT TYR-397 AND TYR-508, AND ENZYME REGULATION.
RX PubMed=7935444;
RA Hata A., Sabe H., Kurosaki T., Takata M., Hanafusa H.;
RT "Functional analysis of Csk in signal transduction through the B-cell
RT antigen receptor.";
RL Mol. Cell. Biol. 14:7306-7313(1994).
RN [10]
RP INTERACTION WITH EPSTEIN-BARR VIRUS LMP2A.
RX PubMed=7895172; DOI=10.1016/S1074-7613(95)80040-9;
RA Miller C.L., Burkhardt A.L., Lee J.H., Stealey B., Longnecker R.,
RA Bolen J.B., Kieff E.;
RT "Integral membrane protein 2 of Epstein-Barr virus regulates
RT reactivation from latency through dominant negative effects on
RT protein-tyrosine kinases.";
RL Immunity 2:155-166(1995).
RN [11]
RP PHOSPHORYLATION AT TYR-508 BY MATK.
RC TISSUE=Platelet;
RX PubMed=9171348; DOI=10.1093/emboj/16.9.2342;
RA Hirao A., Hamaguchi I., Suda T., Yamaguchi N.;
RT "Translocation of the Csk homologous kinase (Chk/Hyl) controls
RT activity of CD36-anchored Lyn tyrosine kinase in thrombin-stimulated
RT platelets.";
RL EMBO J. 16:2342-2351(1997).
RN [12]
RP INTERACTION WITH FCGR2B.
RX PubMed=9232445; DOI=10.1016/S0165-2478(97)00055-2;
RA Sarmay G., Koncz G., Pecht I., Gergely J.;
RT "Fc gamma receptor type IIb induced recruitment of inositol and
RT protein phosphatases to the signal transductory complex of human B-
RT cell.";
RL Immunol. Lett. 57:159-164(1997).
RN [13]
RP INTERACTION WITH KIT, AND PHOSPHORYLATION.
RX PubMed=9341198; DOI=10.1074/jbc.272.43.27450;
RA Linnekin D., DeBerry C.S., Mou S.;
RT "Lyn associates with the juxtamembrane region of c-Kit and is
RT activated by stem cell factor in hematopoietic cell lines and normal
RT progenitor cells.";
RL J. Biol. Chem. 272:27450-27455(1997).
RN [14]
RP FUNCTION IN DNA DAMAGE RESPONSE; APOPTOSIS AND PHOSPHORYLATION OF
RP PTPN6/SHPTP1, AND INTERACTION WITH PTPN6/SHPTP1.
RX PubMed=10574931; DOI=10.1074/jbc.274.49.34663;
RA Yoshida K., Kharbanda S., Kufe D.;
RT "Functional interaction between SHPTP1 and the Lyn tyrosine kinase in
RT the apoptotic response to DNA damage.";
RL J. Biol. Chem. 274:34663-34668(1999).
RN [15]
RP INTERACTION WITH CBLC.
RX PubMed=10362357; DOI=10.1038/sj.onc.1202753;
RA Keane M.M., Ettenberg S.A., Nau M.M., Banerjee P., Cuello M.,
RA Penninger J., Lipkowitz S.;
RT "cbl-3: a new mammalian cbl family protein.";
RL Oncogene 18:3365-3375(1999).
RN [16]
RP FUNCTION IN CD79A PHOSPHORYLATION, AND INTERACTION WITH CD79A.
RX PubMed=10748115; DOI=10.1074/jbc.M909044199;
RA Gaul B.S., Harrison M.L., Geahlen R.L., Burton R.A., Post C.B.;
RT "Substrate recognition by the Lyn protein-tyrosine kinase. NMR
RT structure of the immunoreceptor tyrosine-based activation motif
RT signaling region of the B cell antigen receptor.";
RL J. Biol. Chem. 275:16174-16182(2000).
RN [17]
RP FUNCTION IN REGULATION OF MAST CELL PROLIFERATION, AND MUTAGENESIS OF
RP LYS-275.
RX PubMed=11435302; DOI=10.1182/blood.V98.2.343;
RA O'Laughlin-Bunner B., Radosevic N., Taylor M.L., Shivakrupa R.,
RA DeBerry C., Metcalfe D.D., Zhou M., Lowell C., Linnekin D.;
RT "Lyn is required for normal stem cell factor-induced proliferation and
RT chemotaxis of primary hematopoietic cells.";
RL Blood 98:343-350(2001).
RN [18]
RP INTERACTION WITH PDE4A.
RC TISSUE=Brain;
RX PubMed=11306681;
RA Rena G., Begg F., Ross A., MacKenzie C., McPhee I., Campbell L.,
RA Huston E., Sullivan M., Houslay M.D.;
RT "Molecular cloning, genomic positioning, promoter identification, and
RT characterization of the novel cyclic AMP-specific phosphodiesterase
RT PDE4A10.";
RL Mol. Pharmacol. 59:996-1011(2001).
RN [19]
RP FUNCTION.
RX PubMed=10891478; DOI=10.1128/MCB.20.15.5370-5380.2000;
RA Yoshida K., Weichselbaum R., Kharbanda S., Kufe D.;
RT "Role for Lyn tyrosine kinase as a regulator of stress-activated
RT protein kinase activity in response to DNA damage.";
RL Mol. Cell. Biol. 20:5370-5380(2000).
RN [20]
RP FUNCTION IN DNA DAMAGE RESPONSE; APOPTOSIS AND PHOSPHORYLATION OF
RP PPP1R15A, INTERACTION WITH PPP1R15A, CATALYTIC ACTIVITY, AND
RP MUTAGENESIS OF LYS-275.
RX PubMed=11517336; DOI=10.1073/pnas.191130798;
RA Grishin A.V., Azhipa O., Semenov I., Corey S.J.;
RT "Interaction between growth arrest-DNA damage protein 34 and Src
RT kinase Lyn negatively regulates genotoxic apoptosis.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:10172-10177(2001).
RN [21]
RP FUNCTION IN PHOSPHORYLATION OF KIT AND DOK1, CATALYTIC ACTIVITY, AND
RP INTERACTION WITH KIT.
RX PubMed=11825908; DOI=10.1074/jbc.M200277200;
RA Liang X., Wisniewski D., Strife A., Shivakrupa R., Clarkson B.,
RA Resh M.D.;
RT "Phosphatidylinositol 3-kinase and Src family kinases are required for
RT phosphorylation and membrane recruitment of Dok-1 in c-Kit
RT signaling.";
RL J. Biol. Chem. 277:13732-13738(2002).
RN [22]
RP INTERACTION WITH MUC1.
RX PubMed=12750561;
RA Li Y., Chen W., Ren J., Yu W.H., Li Q., Yoshida K., Kufe D.;
RT "DF3/MUC1 signaling in multiple myeloma cells is regulated by
RT interleukin-7.";
RL Cancer Biol. Ther. 2:187-193(2003).
RN [23]
RP FUNCTION IN THPO-MEDIATED CELL PROLIFERATION.
RX PubMed=14726379; DOI=10.1182/blood-2003-10-3566;
RA Lannutti B.J., Drachman J.G.;
RT "Lyn tyrosine kinase regulates thrombopoietin-induced proliferation of
RT hematopoietic cell lines and primary megakaryocytic progenitors.";
RL Blood 103:3736-3743(2004).
RN [24]
RP SUBCELLULAR LOCATION, DOMAIN, AND MUTAGENESIS OF LYS-275; ASP-346;
RP GLU-353; ASP-498 AND ASP-499.
RX PubMed=15173188; DOI=10.1083/jcb.200403011;
RA Kasahara K., Nakayama Y., Ikeda K., Fukushima Y., Matsuda D.,
RA Horimoto S., Yamaguchi N.;
RT "Trafficking of Lyn through the Golgi caveolin involves the charged
RT residues on alphaE and alphaI helices in the kinase domain.";
RL J. Cell Biol. 165:641-652(2004).
RN [25]
RP REVIEW ON ROLE IN KIT SIGNALING.
RX PubMed=16129412; DOI=10.1016/j.bbrc.2005.08.055;
RA Roskoski R. Jr.;
RT "Signaling by Kit protein-tyrosine kinase--the stem cell factor
RT receptor.";
RL Biochem. Biophys. Res. Commun. 337:1-13(2005).
RN [26]
RP FUNCTION IN PHOSPHORYLATION OF HCLS1.
RX PubMed=15795233; DOI=10.1074/jbc.M412634200;
RA Brunati A.M., Deana R., Folda A., Massimino M.L., Marin O., Ledro S.,
RA Pinna L.A., Donella-Deana A.;
RT "Thrombin-induced tyrosine phosphorylation of HS1 in human platelets
RT is sequentially catalyzed by Syk and Lyn tyrosine kinases and
RT associated with the cellular migration of the protein.";
RL J. Biol. Chem. 280:21029-21035(2005).
RN [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-508, AND MASS
RP SPECTROMETRY.
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer
RT cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [28]
RP FUNCTION.
RX PubMed=16467205; DOI=10.1182/blood-2005-08-3343;
RA Nakata Y., Tomkowicz B., Gewirtz A.M., Ptasznik A.;
RT "Integrin inhibition through Lyn-dependent cross talk from CXCR4
RT chemokine receptors in normal human CD34+ marrow cells.";
RL Blood 107:4234-4239(2006).
RN [29]
RP INTERACTION WITH ABL1.
RX PubMed=16912036; DOI=10.1074/jbc.M605902200;
RA Meyn M.A. III, Wilson M.B., Abdi F.A., Fahey N., Schiavone A.P.,
RA Wu J., Hochrein J.M., Engen J.R., Smithgall T.E.;
RT "Src family kinases phosphorylate the Bcr-Abl SH3-SH2 region and
RT modulate Bcr-Abl transforming activity.";
RL J. Biol. Chem. 281:30907-30916(2006).
RN [30]
RP INTERACTION WITH PAG1, MUTAGENESIS OF TYR-397 AND TYR-508, ENZYME
RP REGULATION, AND UBIQUITINATION.
RX PubMed=16920712; DOI=10.1074/jbc.M602637200;
RA Ingley E., Schneider J.R., Payne C.J., McCarthy D.J., Harder K.W.,
RA Hibbs M.L., Klinken S.P.;
RT "Csk-binding protein mediates sequential enzymatic down-regulation and
RT degradation of Lyn in erythropoietin-stimulated cells.";
RL J. Biol. Chem. 281:31920-31929(2006).
RN [31]
RP INTERACTION WITH TGFB1I1.
RX PubMed=17233630; DOI=10.1042/BJ20061618;
RA Rathore V.B., Okada M., Newman P.J., Newman D.K.;
RT "Paxillin family members function as Csk-binding proteins that
RT regulate Lyn activity in human and murine platelets.";
RL Biochem. J. 403:275-281(2007).
RN [32]
RP FUNCTION IN PHOSPHORYLATION OF LPXN, AND INTERACTION WITH LPXN.
RX PubMed=17640867; DOI=10.1074/jbc.M704625200;
RA Chew V., Lam K.P.;
RT "Leupaxin negatively regulates B cell receptor signaling.";
RL J. Biol. Chem. 282:27181-27191(2007).
RN [33]
RP INTERACTION WITH TOM1L1, AND FUNCTION IN TOM1L1 PHOSPHORYLATION.
RX PubMed=17977829; DOI=10.1074/jbc.M705168200;
RA Zhang J., Suzuki K., Hitomi T., Siraganian R.P.;
RT "TOM1L1 is a Lyn substrate involved in FcepsilonRI signaling in mast
RT cells.";
RL J. Biol. Chem. 282:37669-37677(2007).
RN [34]
RP FUNCTION IN CELL PROLIFERATION AND SURVIVAL, PHOSPHORYLATION,
RP SUBCELLULAR LOCATION, AND ROLE IN DISEASE.
RX PubMed=18056483; DOI=10.1182/blood-2007-04-082099;
RA Dos Santos C., Demur C., Bardet V., Prade-Houdellier N., Payrastre B.,
RA Recher C.;
RT "A critical role for Lyn in acute myeloid leukemia.";
RL Blood 111:2269-2279(2008).
RN [35]
RP FUNCTION, PHOSPHORYLATION AT TYR-397 AND TYR-508, INTERACTION WITH
RP PAG1 AND STAT3, AND SUBCELLULAR LOCATION.
RX PubMed=18070987; DOI=10.1182/blood-2007-05-090985;
RA Tauzin S., Ding H., Khatib K., Ahmad I., Burdevet D.,
RA van Echten-Deckert G., Lindquist J.A., Schraven B., Din N.U.,
RA Borisch B., Hoessli D.C.;
RT "Oncogenic association of the Cbp/PAG adaptor protein with the Lyn
RT tyrosine kinase in human B-NHL rafts.";
RL Blood 111:2310-2320(2008).
RN [36]
RP INTERACTION WITH CBL AND BCR-ABL, FUNCTION IN PHOSPHORYLATION OF
RP BCR-ABL, AND ROLE IN DISEASE.
RX PubMed=18235045; DOI=10.1182/blood-2007-08-109330;
RA Wu J., Meng F., Lu H., Kong L., Bornmann W., Peng Z., Talpaz M.,
RA Donato N.J.;
RT "Lyn regulates BCR-ABL and Gab2 tyrosine phosphorylation and c-Cbl
RT protein stability in imatinib-resistant chronic myelogenous leukemia
RT cells.";
RL Blood 111:3821-3829(2008).
RN [37]
RP SUBCELLULAR LOCATION, MYRISTOYLATION AT GLY-2, AND MUTAGENESIS OF
RP GLY-2; CYS-3 AND LYS-275.
RX PubMed=18817770; DOI=10.1016/j.yexcr.2008.08.019;
RA Ikeda K., Nakayama Y., Togashi Y., Obata Y., Kuga T., Kasahara K.,
RA Fukumoto Y., Yamaguchi N.;
RT "Nuclear localization of Lyn tyrosine kinase mediated by inhibition of
RT its kinase activity.";
RL Exp. Cell Res. 314:3392-3404(2008).
RN [38]
RP FUNCTION IN ADHESION AND CELL MIGRATION.
RX PubMed=18802065;
RA Malik M., Chen Y.-Y., Kienzle M.F., Tomkowicz B.E., Collman R.G.,
RA Ptasznik A.;
RT "Monocyte migration and LFA-1-mediated attachment to brain
RT microvascular endothelia is regulated by SDF-1 alpha through Lyn
RT kinase.";
RL J. Immunol. 181:4632-4637(2008).
RN [39]
RP PHOSPHORYLATION AT TYR-460, AND ROLE IN DISEASE.
RX PubMed=18577747; DOI=10.1093/jnci/djn188;
RA Wu J., Meng F., Kong L.Y., Peng Z., Ying Y., Bornmann W.G.,
RA Darnay B.G., Lamothe B., Sun H., Talpaz M., Donato N.J.;
RT "Association between imatinib-resistant BCR-ABL mutation-negative
RT leukemia and persistent activation of LYN kinase.";
RL J. Natl. Cancer Inst. 100:926-939(2008).
RN [40]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [41]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-11; SER-13; TYR-473 AND
RP TYR-508, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [42]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [43]
RP INTERACTION WITH FASLG.
RX PubMed=19807924; DOI=10.1186/1471-2172-10-53;
RA Voss M., Lettau M., Janssen O.;
RT "Identification of SH3 domain interaction partners of human FasL
RT (CD178) by phage display screening.";
RL BMC Immunol. 10:53-53(2009).
RN [44]
RP INTERACTION WITH ADAM15.
RX PubMed=19718658; DOI=10.1002/jcb.22317;
RA Kleino I., Ortiz R.M., Yritys M., Huovila A.P., Saksela K.;
RT "Alternative splicing of ADAM15 regulates its interactions with
RT cellular SH3 proteins.";
RL J. Cell. Biochem. 108:877-885(2009).
RN [45]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-11; SER-13; SER-228;
RP TYR-306; TYR-316; TYR-473 AND TYR-508, AND MASS SPECTROMETRY.
RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [46]
RP FUNCTION IN PTK2B/PYK2 PHOSPHORYLATION.
RX PubMed=20028775; DOI=10.1189/jlb.0409227;
RA Collins M., Tremblay M., Chapman N., Curtiss M., Rothman P.B.,
RA Houtman J.C.;
RT "The T cell receptor-mediated phosphorylation of Pyk2 tyrosines 402
RT and 580 occurs via a distinct mechanism than other receptor systems.";
RL J. Leukoc. Biol. 87:691-701(2010).
RN [47]
RP INTERACTION WITH NDFIP1 AND NDFIP2, AND UBIQUITINATION.
RX PubMed=20534535; DOI=10.1073/pnas.0911714107;
RA Mund T., Pelham H.R.;
RT "Regulation of PTEN/Akt and MAP kinase signaling pathways by the
RT ubiquitin ligase activators Ndfip1 and Ndfip2.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:11429-11434(2010).
RN [48]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-13, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [49]
RP INTERACTION WITH SCIMP.
RX PubMed=21930792; DOI=10.1128/MCB.05817-11;
RA Draber P., Vonkova I., Stepanek O., Hrdinka M., Kucova M.,
RA Skopcova T., Otahal P., Angelisova P., Horejsi V., Yeung M., Weiss A.,
RA Brdicka T.;
RT "SCIMP, a transmembrane adapter protein involved in major
RT histocompatibility complex class II signaling.";
RL Mol. Cell. Biol. 31:4550-4562(2011).
RN [50]
RP REVIEW.
RX PubMed=15220000; DOI=10.1016/j.molimm.2004.04.010;
RA Lowell C.A.;
RT "Src-family kinases: rheostats of immune cell signaling.";
RL Mol. Immunol. 41:631-643(2004).
RN [51]
RP REVIEW ON ROLE IN B CELLS.
RX PubMed=15489917; DOI=10.1038/sj.onc.1208075;
RA Gauld S.B., Cambier J.C.;
RT "Src-family kinases in B-cell development and signaling.";
RL Oncogene 23:8001-8006(2004).
RN [52]
RP REVIEW ON ROLE IN B CELLS.
RX PubMed=15664155; DOI=10.1016/j.immuni.2004.12.004;
RA Xu Y., Harder K.W., Huntington N.D., Hibbs M.L., Tarlinton D.M.;
RT "Lyn tyrosine kinase: accentuating the positive and the negative.";
RL Immunity 22:9-18(2005).
RN [53]
RP REVIEW ON ROLE IN GROWTH FACTOR SIGNALING.
RX PubMed=16801133; DOI=10.1080/08977190600581327;
RA Hibbs M.L., Harder K.W.;
RT "The duplicitous nature of the Lyn tyrosine kinase in growth factor
RT signaling.";
RL Growth Factors 24:137-149(2006).
RN [54]
RP REVIEW ON ROLE IN MAST CELLS.
RX PubMed=18772004; DOI=10.1016/S0065-2776(08)00403-3;
RA Rivera J., Fierro N.A., Olivera A., Suzuki R.;
RT "New insights on mast cell activation via the high affinity receptor
RT for IgE.";
RL Adv. Immunol. 98:85-120(2008).
RN [55]
RP REVIEW ON ROLE IN MYELOID CELL FUNCTION AND SIGNALING.
RX PubMed=19290919; DOI=10.1111/j.1600-065X.2008.00758.x;
RA Scapini P., Pereira S., Zhang H., Lowell C.A.;
RT "Multiple roles of Lyn kinase in myeloid cell signaling and
RT function.";
RL Immunol. Rev. 228:23-40(2009).
RN [56]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-11 AND SER-13, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [57]
RP STRUCTURE BY NMR OF 61-123 IN COMPLEX WITH SAIMIRIINE HERPESVIRUS 2
RP TYROSINE KINASE INTERACTING PROTEIN.
RX PubMed=11955060; DOI=10.1021/bi015986j;
RA Schweimer K., Hoffmann S., Bauer F., Friedrich U., Kardinal C.,
RA Feller S.M., Biesinger B., Sticht H.;
RT "Structural investigation of the binding of a herpesviral protein to
RT the SH3 domain of tyrosine kinase Lck.";
RL Biochemistry 41:5120-5130(2002).
RN [58]
RP STRUCTURE BY NMR OF 61-122, AND INTERACTION WITH HERPESVIRUS TYROSINE
RP KINASE INTERACTING PROTEIN.
RX PubMed=16155203; DOI=10.1110/ps.051563605;
RA Bauer F., Schweimer K., Meiselbach H., Hoffmann S., Rosch P.,
RA Sticht H.;
RT "Structural characterization of Lyn-SH3 domain in complex with a
RT herpesviral protein reveals an extended recognition motif that
RT enhances binding affinity.";
RL Protein Sci. 14:2487-2498(2005).
RN [59]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 233-512 IN COMPLEX WITH
RP STAUROSPORINE.
RX PubMed=19857964; DOI=10.1016/j.bmcl.2009.10.038;
RA Miyano N., Kinoshita T., Nakai R., Kirii Y., Yokota K., Tada T.;
RT "Structural basis for the inhibitor recognition of human Lyn kinase
RT domain.";
RL Bioorg. Med. Chem. Lett. 19:6557-6560(2009).
RN [60]
RP VARIANT [LARGE SCALE ANALYSIS] TYR-385.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C.,
RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S.,
RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S.,
RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E.,
RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J.,
RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K.,
RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T.,
RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P.,
RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E.,
RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E.,
RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T.,
RA Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Non-receptor tyrosine-protein kinase that transmits
CC signals from cell surface receptors and plays an important role in
CC the regulation of innate and adaptive immune responses,
CC hematopoiesis, responses to growth factors and cytokines, integrin
CC signaling, but also responses to DNA damage and genotoxic agents.
CC Functions primarily as negative regulator, but can also function
CC as activator, depending on the context. Required for the
CC initiation of the B-cell response, but also for its down-
CC regulation and termination. Plays an important role in the
CC regulation of B-cell differentiation, proliferation, survival and
CC apoptosis, and is important for immune self-tolerance. Acts
CC downstream of several immune receptors, including the B-cell
CC receptor, CD79A, CD79B, CD5, CD19, CD22, FCER1, FCGR2, FCGR1A,
CC TLR2 and TLR4. Plays a role in the inflammatory response to
CC bacterial lipopolysaccharide. Mediates the responses to cytokines
CC and growth factors in hematopoietic progenitors, platelets,
CC erythrocytes, and in mature myeloid cells, such as dendritic
CC cells, neutrophils and eosinophils. Acts downstream of EPOR, KIT,
CC MPL, the chemokine receptor CXCR4, as well as the receptors for
CC IL3, IL5 and CSF2. Plays an important role in integrin signaling.
CC Regulates cell proliferation, survival, differentiation,
CC migration, adhesion, degranulation, and cytokine release. Down-
CC regulates signaling pathways by phosphorylation of immunoreceptor
CC tyrosine-based inhibitory motifs (ITIM), that then serve as
CC binding sites for phosphatases, such as PTPN6/SHP-1, PTPN11/SHP-2
CC and INPP5D/SHIP-1, that modulate signaling by dephosphorylation of
CC kinases and their substrates. Phosphorylates LIME1 in response to
CC CD22 activation. Phosphorylates BTK, CBL, CD5, CD19, CD72, CD79A,
CC CD79B, CSF2RB, DOK1, HCLS1, LILRB3/PIR-B, MS4A2/FCER1B,
CC PTK2B/PYK2, SYK and TEC. Promotes phosphorylation of SIRPA,
CC PTPN6/SHP-1, PTPN11/SHP-2 and INPP5D/SHIP-1. Mediates
CC phosphorylation of the BCR-ABL fusion protein. Required for rapid
CC phosphorylation of FER in response to FCER1 activation. Mediates
CC KIT phosphorylation. Acts as an effector of EPOR (erythropoietin
CC receptor) in controlling KIT expression and may play a role in
CC erythroid differentiation during the switch between proliferation
CC and maturation. Depending on the context, activates or inhibits
CC several signaling cascades. Regulates phosphatidylinositol 3-
CC kinase activity and AKT1 activation. Regulates activation of the
CC MAP kinase signaling cascade, including activation of MAP2K1/MEK1,
CC MAPK1/ERK2, MAPK3/ERK1, MAPK8/JNK1 and MAPK9/JNK2. Mediates
CC activation of STAT5A and/or STAT5B. Phosphorylates LPXN on 'Tyr-
CC 72'.
CC -!- CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a
CC [protein]-L-tyrosine phosphate.
CC -!- ENZYME REGULATION: Subject to autoinhibition, mediated by
CC intramolecular interactions between the SH2 domain and the C-
CC terminal phosphotyrosine. Phosphorylation at Tyr-397 is required
CC for optimal activity. Phosphorylated by CSK at Tyr-508;
CC phosphorylation at Tyr-508 inhibits kinase activity. Kinase
CC activity is modulated by dephosphorylation by PTPRC/CD45.
CC Inhibited by Dasatinib, PP2, and SU6656.
CC -!- SUBUNIT: Interacts with TEC. Interacts (via SH2 domain) with FLT3
CC (tyrosine phosphorylated). Interacts with LIME1 and with CD79A
CC upon activation of the B-cell antigen receptor. Interacts with the
CC B-cell receptor complex. Interacts with phosphorylated THEMIS2.
CC Interacts with EPOR. Interacts with MS4A2/FCER1B. Interaction (via
CC the SH2 and SH3 domains) with MUC1 is stimulated by IL7 and the
CC subsequent phosphorylation increases the binding between MUC1 and
CC CTNNB1/beta-catenin. Interacts with ADAM15. Interacts with NDFIP2
CC and more weakly with NDFIP1. Interacts with FASLG. Interacts with
CC KIT. Interacts with HCLS1. Interacts with FCGR2B. Interacts with
CC FCGR1A; the interaction may be indirect. Interacts with CD19,
CC CD22, CD79A and CD79B. Interacts (via SH3 domain) with CBLC,
CC PPP1R15A and PDE4A. Interacts with TGFB1I1. Interacts (via SH3
CC domain) with PIK3R1, the regulatory subunit of
CC phosphatidylinositol 3-kinase; this interaction enhances
CC phosphatidylinositol 3-kinase activity. Interacts with CSF2RB, the
CC common subunit of the IL3, IL5 and CSF2 receptors. Interacts with
CC PAG1; identified in a complex with PAG1 and STAT3. Interacts with
CC ABL1. Interacts with PTPN6/SHP-1. Interacts (via SH3 domain) with
CC SCIMP (via proline-rich region). Interacts with LPXN (via LD motif
CC 3) and the interaction is induced upon B-cell antigen receptor
CC (BCR) activation. Interacts (via SH3-domain) with ANKRD54 (via
CC ankyrin repeat region) in an activation-independent status of LYN.
CC Forms a multiprotein complex with ANKRD54 and HCLS1. Interacts
CC with Epstein-Barr virus LMP2A. Interacts with Herpes virus saimiri
CC tyrosine kinase interacting protein (Tip).
CC -!- INTERACTION:
CC O92972:- (xeno); NbExp=2; IntAct=EBI-79452, EBI-710506;
CC P22575:- (xeno); NbExp=3; IntAct=EBI-79452, EBI-866709;
CC P27958:- (xeno); NbExp=5; IntAct=EBI-79452, EBI-706378;
CC Q9WMX2:- (xeno); NbExp=3; IntAct=EBI-79452, EBI-710918;
CC Q8R5G7:Arap3 (xeno); NbExp=2; IntAct=EBI-79452, EBI-621463;
CC P20273:CD22; NbExp=2; IntAct=EBI-79452, EBI-78277;
CC P25063:CD24; NbExp=6; IntAct=EBI-79452, EBI-6267018;
CC P11049:CD37; NbExp=5; IntAct=EBI-79452, EBI-6139068;
CC P46527:CDKN1B; NbExp=2; IntAct=EBI-79452, EBI-519280;
CC P00533:EGFR; NbExp=3; IntAct=EBI-79452, EBI-297353;
CC Q9HCN6:GP6; NbExp=2; IntAct=EBI-79452, EBI-515278;
CC P05556:ITGB1; NbExp=4; IntAct=EBI-79452, EBI-703066;
CC P33993:MCM7; NbExp=5; IntAct=EBI-6895930, EBI-355924;
CC -!- SUBCELLULAR LOCATION: Cell membrane. Nucleus. Cytoplasm.
CC Cytoplasm, perinuclear region. Golgi apparatus. Note=Accumulates
CC in the nucleus by inhibition of CRM1-mediated nuclear export.
CC Nuclear accumulation is increased by inhibition of its kinase
CC activity. The trafficking from the Golgi apparatus to the plasma
CC membrane occurs in a kinase domain-dependent but kinase activity
CC independent manner and is mediated by exocytic vesicular
CC transport. Detected on plasma membrane lipid rafts.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=LYN A, p56lyn;
CC IsoId=P07948-1; Sequence=Displayed;
CC Name=2; Synonyms=LYN B, p53lyn;
CC IsoId=P07948-2; Sequence=VSP_005002;
CC -!- TISSUE SPECIFICITY: Detected in monocytes (at protein level).
CC Detected in placenta, and in fetal brain, lung, liver and kidney.
CC Widely expressed in a variety of organs, tissues, and cell types
CC such as epidermoid, hematopoietic, and neuronal cells. Expressed
CC in primary neuroblastoma tumors.
CC -!- DOMAIN: The protein kinase domain plays an important role in its
CC localization in the cell membrane.
CC -!- PTM: Ubiquitinated by CBL, leading to its degradation.
CC Ubiquitination is SH3-dependent.
CC -!- PTM: Autophosphorylated. Phosphorylated on tyrosine residues in
CC response to KIT signaling. Phosphorylation at Tyr-397 is required
CC for optimal activity. Phosphorylation at Tyr-508 inhibits kinase
CC activity. Phosphorylated at Tyr-508 by CSK. Dephosphorylated by
CC PTPRC/CD45. Becomes rapidly phosphorylated upon activation of the
CC B-cell receptor and the immunoglobulin receptor FCGR1A.
CC -!- DISEASE: Note=Constitutively phosphorylated and activated in cells
CC from a number of chronic myelogenous leukemia (CML) and acute
CC myeloid leukemia (AML) patients. Mediates phosphorylation of the
CC BCR-ABL fusion protein. Abnormally elevated expression levels or
CC activation of LYN signaling may play a role in survival and
CC proliferation of some types of cancer cells.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. SRC subfamily.
CC -!- SIMILARITY: Contains 1 protein kinase domain.
CC -!- SIMILARITY: Contains 1 SH2 domain.
CC -!- SIMILARITY: Contains 1 SH3 domain.
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DR EMBL; M16038; AAA59540.1; -; mRNA.
DR EMBL; M79321; AAB50019.1; -; mRNA.
DR EMBL; BC075001; AAH75001.1; -; mRNA.
DR EMBL; BC075002; AAH75002.1; -; mRNA.
DR EMBL; BC126456; AAI26457.1; -; mRNA.
DR EMBL; BC126458; AAI26459.1; -; mRNA.
DR PIR; A26719; TVHULY.
DR RefSeq; NP_001104567.1; NM_001111097.2.
DR RefSeq; NP_002341.1; NM_002350.3.
DR RefSeq; XP_005251289.1; XM_005251232.1.
DR RefSeq; XP_005251290.1; XM_005251233.1.
DR UniGene; Hs.491767; -.
DR UniGene; Hs.545418; -.
DR PDB; 1W1F; NMR; -; A=61-123.
DR PDB; 1WA7; NMR; -; A=61-123.
DR PDB; 3A4O; X-ray; 3.00 A; X=233-512.
DR PDBsum; 1W1F; -.
DR PDBsum; 1WA7; -.
DR PDBsum; 3A4O; -.
DR ProteinModelPortal; P07948; -.
DR SMR; P07948; 64-512.
DR DIP; DIP-1056N; -.
DR IntAct; P07948; 46.
DR MINT; MINT-200655; -.
DR STRING; 9606.ENSP00000376688; -.
DR BindingDB; P07948; -.
DR ChEMBL; CHEMBL2363074; -.
DR GuidetoPHARMACOLOGY; 2060; -.
DR PhosphoSite; P07948; -.
DR DMDM; 125480; -.
DR REPRODUCTION-2DPAGE; P07948; -.
DR PaxDb; P07948; -.
DR PRIDE; P07948; -.
DR DNASU; 4067; -.
DR Ensembl; ENST00000519728; ENSP00000428924; ENSG00000254087.
DR Ensembl; ENST00000520220; ENSP00000428424; ENSG00000254087.
DR GeneID; 4067; -.
DR KEGG; hsa:4067; -.
DR UCSC; uc003xsk.4; human.
DR CTD; 4067; -.
DR GeneCards; GC08P056792; -.
DR HGNC; HGNC:6735; LYN.
DR HPA; CAB004492; -.
DR HPA; HPA001231; -.
DR MIM; 165120; gene.
DR neXtProt; NX_P07948; -.
DR PharmGKB; PA30498; -.
DR eggNOG; COG0515; -.
DR HOGENOM; HOG000233858; -.
DR HOVERGEN; HBG008761; -.
DR KO; K05854; -.
DR OMA; ISSMIKH; -.
DR PhylomeDB; P07948; -.
DR BRENDA; 2.7.10.2; 2681.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_604; Hemostasis.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; P07948; -.
DR ChiTaRS; LYN; human.
DR EvolutionaryTrace; P07948; -.
DR GeneWiki; LYN; -.
DR GenomeRNAi; 4067; -.
DR NextBio; 15944; -.
DR PMAP-CutDB; P07948; -.
DR PRO; PR:P07948; -.
DR ArrayExpress; P07948; -.
DR Bgee; P07948; -.
DR CleanEx; HS_LYN; -.
DR Genevestigator; P07948; -.
DR GO; GO:0034666; C:alpha2-beta1 integrin complex; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IDA:UniProtKB.
DR GO; GO:0030061; C:mitochondrial crista; IEA:Ensembl.
DR GO; GO:0005758; C:mitochondrial intermembrane space; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0014069; C:postsynaptic density; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0043208; F:glycosphingolipid binding; IEA:Ensembl.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; TAS:Reactome.
DR GO; GO:0004716; F:receptor signaling protein tyrosine kinase activity; TAS:ProtInc.
DR GO; GO:0030262; P:apoptotic nuclear changes; IDA:UniProtKB.
DR GO; GO:0001782; P:B cell homeostasis; ISS:UniProtKB.
DR GO; GO:0050853; P:B cell receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0031668; P:cellular response to extracellular stimulus; IEA:Ensembl.
DR GO; GO:0034605; P:cellular response to heat; IEA:Ensembl.
DR GO; GO:0071300; P:cellular response to retinoic acid; IMP:BHF-UCL.
DR GO; GO:0050663; P:cytokine secretion; IEA:Ensembl.
DR GO; GO:0097028; P:dendritic cell differentiation; ISS:UniProtKB.
DR GO; GO:0030218; P:erythrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0002774; P:Fc receptor mediated inhibitory signaling pathway; ISS:UniProtKB.
DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome.
DR GO; GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome.
DR GO; GO:0002553; P:histamine secretion by mast cell; IEA:Ensembl.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IC:UniProtKB.
DR GO; GO:0060397; P:JAK-STAT cascade involved in growth hormone signaling pathway; TAS:Reactome.
DR GO; GO:0050900; P:leukocyte migration; TAS:Reactome.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0030889; P:negative regulation of B cell proliferation; IEA:Ensembl.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0050777; P:negative regulation of immune response; TAS:UniProtKB.
DR GO; GO:0043407; P:negative regulation of MAP kinase activity; ISS:UniProtKB.
DR GO; GO:0070667; P:negative regulation of mast cell proliferation; ISS:UniProtKB.
DR GO; GO:0002762; P:negative regulation of myeloid leukocyte differentiation; IEA:Ensembl.
DR GO; GO:0034136; P:negative regulation of toll-like receptor 2 signaling pathway; ISS:UniProtKB.
DR GO; GO:0034144; P:negative regulation of toll-like receptor 4 signaling pathway; ISS:UniProtKB.
DR GO; GO:0031175; P:neuron projection development; IEA:Ensembl.
DR GO; GO:0014003; P:oligodendrocyte development; IEA:Ensembl.
DR GO; GO:0030168; P:platelet activation; TAS:Reactome.
DR GO; GO:0002576; P:platelet degranulation; ISS:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; IEA:Ensembl.
DR GO; GO:0051272; P:positive regulation of cellular component movement; IDA:UniProtKB.
DR GO; GO:2000670; P:positive regulation of dendritic cell apoptotic process; ISS:UniProtKB.
DR GO; GO:0060369; P:positive regulation of Fc receptor mediated stimulatory signaling pathway; IEA:Ensembl.
DR GO; GO:0060252; P:positive regulation of glial cell proliferation; IEA:Ensembl.
DR GO; GO:0070668; P:positive regulation of mast cell proliferation; IMP:UniProtKB.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IMP:BHF-UCL.
DR GO; GO:0070447; P:positive regulation of oligodendrocyte progenitor proliferation; IEA:Ensembl.
DR GO; GO:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; IEA:Ensembl.
DR GO; GO:0070304; P:positive regulation of stress-activated protein kinase signaling cascade; IDA:UniProtKB.
DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; ISS:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0002902; P:regulation of B cell apoptotic process; IEA:Ensembl.
DR GO; GO:0050855; P:regulation of B cell receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0033628; P:regulation of cell adhesion mediated by integrin; IMP:UniProtKB.
DR GO; GO:0001817; P:regulation of cytokine production; ISS:UniProtKB.
DR GO; GO:0050707; P:regulation of cytokine secretion; IEA:Ensembl.
DR GO; GO:0045646; P:regulation of erythrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0050727; P:regulation of inflammatory response; IEA:Ensembl.
DR GO; GO:0043304; P:regulation of mast cell degranulation; ISS:UniProtKB.
DR GO; GO:0090025; P:regulation of monocyte chemotaxis; IMP:UniProtKB.
DR GO; GO:0090330; P:regulation of platelet aggregation; ISS:UniProtKB.
DR GO; GO:0051279; P:regulation of release of sequestered calcium ion into cytosol; IEA:Ensembl.
DR GO; GO:0043200; P:response to amino acid stimulus; IEA:Ensembl.
DR GO; GO:0048678; P:response to axon injury; IEA:Ensembl.
DR GO; GO:0009743; P:response to carbohydrate stimulus; IEA:Ensembl.
DR GO; GO:0032868; P:response to insulin stimulus; IEA:Ensembl.
DR GO; GO:0014070; P:response to organic cyclic compound; IEA:Ensembl.
DR GO; GO:0006991; P:response to sterol depletion; IEA:Ensembl.
DR GO; GO:0009636; P:response to toxic substance; IEA:Ensembl.
DR GO; GO:0031295; P:T cell costimulation; TAS:Reactome.
DR GO; GO:0002513; P:tolerance induction to self antigen; ISS:UniProtKB.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR011009; Kinase-like_dom.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR001452; SH3_domain.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR Pfam; PF07714; Pkinase_Tyr; 1.
DR Pfam; PF00017; SH2; 1.
DR Pfam; PF00018; SH3_1; 1.
DR PRINTS; PR00401; SH2DOMAIN.
DR PRINTS; PR00452; SH3DOMAIN.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00252; SH2; 1.
DR SMART; SM00326; SH3; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR PROSITE; PS50001; SH2; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Alternative splicing; ATP-binding;
KW Cell membrane; Complete proteome; Cytoplasm; Golgi apparatus;
KW Host-virus interaction; Immunity; Inflammatory response;
KW Innate immunity; Kinase; Lipoprotein; Membrane; Myristate;
KW Nucleotide-binding; Nucleus; Palmitate; Phosphoprotein; Polymorphism;
KW Proto-oncogene; Reference proteome; SH2 domain; SH3 domain;
KW Transferase; Tyrosine-protein kinase; Ubl conjugation.
FT INIT_MET 1 1 Removed (Probable).
FT CHAIN 2 512 Tyrosine-protein kinase Lyn.
FT /FTId=PRO_0000088129.
FT DOMAIN 63 123 SH3.
FT DOMAIN 129 226 SH2.
FT DOMAIN 247 501 Protein kinase.
FT NP_BIND 253 261 ATP (By similarity).
FT ACT_SITE 367 367 Proton acceptor (By similarity).
FT BINDING 275 275 ATP (By similarity).
FT MOD_RES 6 6 Phosphoserine.
FT MOD_RES 11 11 Phosphoserine.
FT MOD_RES 13 13 Phosphoserine.
FT MOD_RES 30 30 Phosphothreonine.
FT MOD_RES 32 32 Phosphotyrosine.
FT MOD_RES 37 37 Phosphothreonine.
FT MOD_RES 193 193 Phosphotyrosine.
FT MOD_RES 194 194 Phosphotyrosine.
FT MOD_RES 228 228 Phosphoserine.
FT MOD_RES 265 265 Phosphotyrosine.
FT MOD_RES 306 306 Phosphotyrosine.
FT MOD_RES 316 316 Phosphotyrosine.
FT MOD_RES 397 397 Phosphotyrosine; by autocatalysis.
FT MOD_RES 460 460 Phosphotyrosine.
FT MOD_RES 473 473 Phosphotyrosine.
FT MOD_RES 489 489 Phosphothreonine.
FT MOD_RES 502 502 Phosphothreonine.
FT MOD_RES 508 508 Phosphotyrosine; by autocatalysis, CSK
FT and MATK.
FT LIPID 2 2 N-myristoyl glycine (Probable).
FT LIPID 3 3 S-palmitoyl cysteine (Probable).
FT VAR_SEQ 23 43 Missing (in isoform 2).
FT /FTId=VSP_005002.
FT VARIANT 385 385 D -> Y (in a breast pleomorphic lobular
FT carcinoma sample; somatic mutation).
FT /FTId=VAR_041737.
FT MUTAGEN 2 2 G->A: Loss of localization to the cell
FT membrane; when associated with A-3.
FT MUTAGEN 3 3 C->A: Loss of localization to the cell
FT membrane; when associated with A-2.
FT MUTAGEN 275 275 K->A: Loss of activity and no effect on
FT localization to the cell membrane.
FT Abundant localization in the nucleus;
FT when associated with A-2 and A-3.
FT MUTAGEN 275 275 K->L,R: Loss of kinase activity.
FT MUTAGEN 346 346 D->A: Impedes the trafficking from the
FT Golgi apparatus toward the cell membrane;
FT when associated with A-353; A-498 and A-
FT 499.
FT MUTAGEN 353 353 E->A: Impedes the trafficking from the
FT Golgi apparatus toward the cell membrane;
FT when associated with A-346; A-498 and A-
FT 499.
FT MUTAGEN 397 397 Y->F: Strongly reduced kinase activity.
FT MUTAGEN 498 498 D->A: Impedes the trafficking from the
FT Golgi apparatus toward the cell membrane;
FT when associated with A-346; A-353 and A-
FT 499.
FT MUTAGEN 499 499 D->A: Impedes the trafficking from the
FT Golgi apparatus toward the cell membrane;
FT when associated with A-346; A-353 and A-
FT 498.
FT MUTAGEN 508 508 Y->F: Abolishes autoinhibition and
FT thereby increases kinase activity.
FT STRAND 66 72
FT STRAND 78 80
FT STRAND 89 95
FT STRAND 97 104
FT TURN 105 107
FT STRAND 110 114
FT TURN 115 117
FT STRAND 118 120
FT STRAND 259 262
FT STRAND 265 269
FT STRAND 273 275
FT STRAND 284 286
FT TURN 287 289
FT HELIX 290 293
FT TURN 294 297
FT STRAND 306 309
FT STRAND 311 314
FT STRAND 316 319
FT HELIX 327 330
FT HELIX 334 338
FT HELIX 341 360
FT STRAND 372 375
FT STRAND 381 383
FT HELIX 407 409
FT HELIX 412 416
FT HELIX 422 437
FT TURN 449 451
FT HELIX 452 457
FT STRAND 466 468
FT HELIX 470 477
FT TURN 478 480
FT TURN 484 486
FT HELIX 490 502
SQ SEQUENCE 512 AA; 58574 MW; 408D3D461204E378 CRC64;
MGCIKSKGKD SLSDDGVDLK TQPVRNTERT IYVRDPTSNK QQRPVPESQL LPGQRFQTKD
PEEQGDIVVA LYPYDGIHPD DLSFKKGEKM KVLEEHGEWW KAKSLLTKKE GFIPSNYVAK
LNTLETEEWF FKDITRKDAE RQLLAPGNSA GAFLIRESET LKGSFSLSVR DFDPVHGDVI
KHYKIRSLDN GGYYISPRIT FPCISDMIKH YQKQADGLCR RLEKACISPK PQKPWDKDAW
EIPRESIKLV KRLGAGQFGE VWMGYYNNST KVAVKTLKPG TMSVQAFLEE ANLMKTLQHD
KLVRLYAVVT REEPIYIITE YMAKGSLLDF LKSDEGGKVL LPKLIDFSAQ IAEGMAYIER
KNYIHRDLRA ANVLVSESLM CKIADFGLAR VIEDNEYTAR EGAKFPIKWT APEAINFGCF
TIKSDVWSFG ILLYEIVTYG KIPYPGRTNA DVMTALSQGY RMPRVENCPD ELYDIMKMCW
KEKAEERPTF DYLQSVLDDF YTATEGQYQQ QP
//
MIM
165120
*RECORD*
*FIELD* NO
165120
*FIELD* TI
*165120 V-YES-1 YAMAGUCHI SARCOMA VIRAL RELATED ONCOGENE HOMOLOG; LYN
;;ONCOGENE LYN
read more*FIELD* TX
CLONING
Using a v-yes DNA as the probe, Yamanashi et al. (1987) screened a human
cDNA library made from placental RNA and derived DNA clones representing
a novel genetic locus termed LYN. Nucleotide sequencing showed that LYN
encodes a novel tyrosine kinase. Northern hybridization analysis showed
that a 3.2-kb LYN mRNA was expressed in a variety of tissues of the
human fetus. The pattern of expression was different from those of
related genes such as YES (164880).
GENE FUNCTION
Parravicini et al. (2002) noted that Lyn deficiency impairs some mast
cell functions, but degranulation and cytokine production are intact. In
Gab2 (606203)-deficient mice, on the other hand, degranulation and
cytokine production are impaired. Using immunoblot analysis, they showed
that although Lyn is essential for Syk (600085) activation and Lat
(602354) phosphorylation after Fcer1 (see FCER1G; 147139) aggregation,
neither Lyn nor Lat are necessary for Gab2 phosphorylation. RT-PCR and
coimmunoprecipitation analyses demonstrated abundant Fyn (137025)
expression in mast cells and an association with Gab2. In cells lacking
Fyn, neither Gab2 nor Akt (164730) were phosphorylated. Functional
analysis showed that Lyn -/- mast cells exhibited hyperdegranulation and
enhanced PI3K (see 601232) activity and Akt phosphorylation, whereas in
Fyn -/- mast cells the degranulation response was inhibited. The
inhibition was associated with decreased binding of PI3K with Gab2.
Parravicini et al. (2002) observed that the degranulation response was
independent of Fcer1 stimulation in Fyn-deficient mast cells and that
degranulation was dependent on PI3K in wildtype and mutant cell lines.
The degranulation response was dependent on a rise in intracellular
calcium that was inhibited in Lyn-deficient mast cells but intact in
Fyn-deficient cells. Degranulation proceeded in Lyn -/- cells due to
increased activation and constitutive phosphorylation of the
calcium-independent protein kinase C delta isoform (PRKCD; 176977).
Parravicini et al. (2002) concluded that Fyn- and Lyn-initiated pathways
synergize in late events at the level of protein kinase C and calcium,
respectively, to regulate mast cell degranulation.
Yoo et al. (2011) identified Lyn as a redox sensor that mediates initial
neutrophil recruitment to wounds in zebrafish larvae. Lyn activation in
neutrophils is dependent on wound-derived H2O2 after tissue injury, and
inhibition of Lyn attenuates neutrophil wound recruitment. Inhibition of
Src family kinase (SFK) also disrupted H2O2-mediated chemotaxis of
primary human neutrophils. In vitro analysis identified a single
cysteine residue, C466, as being responsible for direct
oxidation-mediated activation of Lyn. Furthermore, transgenic
tissue-specific reconstitution with wildtype Lyn and a cysteine mutant
revealed that Lyn C466 is important for the neutrophil wound response
and downstream signaling in vivo. Yoo et al. (2011) concluded that this
was the first identification of a physiologic redox sensor that mediates
leukocyte wound attraction in multicellular organisms.
MAPPING
By hybridization analysis of DNA from sorted chromosomes, Yamanashi et
al. (1987) mapped the LYN gene to chromosome 8q13-qter.
ANIMAL MODEL
Hibbs et al. (1995) demonstrated that mice homozygous for a disruption
of the Lyn locus display abnormalities associated with the B-lymphocyte
lineage and in mast cell function. Despite reduced numbers of
recirculating B lymphocytes, the homozygous deficient mice are
immunoglobulin M hyperglobulinemic. Lyn-deficient mice show IgM
hyperglobulinemia. Immune responses to T-independent and T-dependent
antigens were affected. The deficient mice failed to mediate an allergic
response to IgE cross-linking, indicating that activation of Lyn plays
an indispensable role in signaling by the high-affinity IgE receptor
(FCER). Homozygous deficient mice had circulating autoreactive
antibodies, and many showed severe glomerulonephritis caused by the
deposition of IgG immune complexes in the kidney, a pathology
reminiscent of systemic lupus erythematosus. Hibbs et al. (1995) stated
that, collectively, these results implicated LYN as having an
indispensable role in immunoglobulin-mediated signaling, particularly in
establishing B cell tolerance.
Harder et al. (2001) generated mice with a gain-of-function Lyn mutation
(tyr508 to phe, which they referred to as 'up') analogous to the
tyr527-to-phe activating mutation in the mouse Src gene (190090)
(Webster et al., 1995). Even aging mice with the Lyn up/up phenotype did
not display hematologic malignancies, unlike Lyn -/- mice, which
developed splenomegaly, increased myeloid progenitors, and
monocyte/macrophage tumors. Biochemical analysis revealed that Lyn is
essential in establishing ITIM (immunoreceptor tyrosine-based inhibitory
motif)-dependent signaling and for the activation of specific protein
tyrosine phosphatases within myeloid cells, which may underlie the
susceptibility of Lyn -/- mice to tumorigenesis.
Hasegawa et al. (2001) generated mice deficient in both Cd19 (107265)
and Lyn. Cd19 deficiency suppressed the hyperresponsive phenotype of Lyn
-/- B cells and autoimmunity characterized by serum autoantibodies and
immune complex-mediated glomerulonephritis in Lyn -/- mice. Cd19/Lyn -/-
mice had additional reduction of primitive, predominantly IgM-secreting
B1 lymphocytes. Cd19 deficiency inhibited activation of Src family
protein tyrosine kinase-dependent signaling pathways and delayed
enhanced intracellular calcium responses following B-cell antigen
receptor ligation in Lyn -/- B cells. Hasegawa et al. (2001) concluded
that Cd19 expression is required for the development of autoimmunity in
Lyn -/- mice.
SYK controls pre-B cell development but does not affect NFKB (164011)
induction. Saijo et al. (2003) showed that mice triple-deficient in the
Src family protein tyrosine kinases (SFKs) Blk (191305), Fyn, and Lyn,
but not single-deficient or Syk-deficient mice, had impaired Nfkb
induction and B-cell development. The impairment of Nfkb induction could
be overcome by protein kinase C-lambda (see 176982) activation. Saijo et
al. (2003) suggested that there are 2 separate pathways in pre-B cell
receptor signaling, one SFK-dependent and the other SYK-dependent, that
contribute critically to pre-B cell development.
*FIELD* RF
1. Harder, K. W.; Parsons, L. M.; Armes, J.; Evans, N.; Kountouri,
N.; Clark, R.; Quillici, C.; Grail, D.; Hodgson, G. S.; Dunn, A. R.;
Hibbs, M. L.: Gain- and loss-of-function Lyn mutant mice define a
critical inhibitory role for Lyn in the myeloid lineage. Immunity 15:
603-615, 2001.
2. Hasegawa, M.; Fujimoto, M.; Poe, J. C.; Steeber, D. A.; Lowell,
C. A.; Tedder, T. F.: A CD19-dependent signaling pathway regulates
autoimmunity in Lyn-deficient mice. J. Immun. 167: 2469-2478, 2001.
3. Hibbs, M. L.; Tarlinton, D. M.; Armes, J.; Grail, D.; Hodgson,
G.; Maglitto, R.; Stacker, S. A.; Dunn, A. R.: Multiple defects in
the immune system of Lyn-deficient mice, culminating in autoimmune
disease. Cell 83: 301-311, 1995.
4. Parravicini, V.; Gadina, M.; Kovarova, M.; Odom, S.; Gonzalez-Espinosa,
C.; Furumoto, Y.; Saitoh, S.; Samelson, L. E.; O'Shea, J. J.; Rivera,
J.: Fyn kinase initiates complementary signals required for IgE-dependent
mast cell degranulation. Nature Immun. 3: 741-748, 2002.
5. Saijo, K.; Schmedt, C.; Su, I.; Karasuyama, H.; Lowell, C. A.;
Reth, M.; Adachi, T.; Patke, A.; Santana, A.; Tarakhovsky, A.: Essential
role of Src-family protein tyrosine kinases in NF-kappa-B activation
during B cell development. Nature Immun. 4: 274-279, 2003.
6. Webster, M. A.; Cardiff, R. D.; Muller, W. J.: Induction of mammary
epithelial hyperplasias and mammary tumors in transgenic mice expressing
a murine mammary tumor virus/activated c-src fusion gene. Proc. Nat.
Acad. Sci. 92: 7849-7853, 1995.
7. Yamanashi, Y.; Fukushige, S.-I.; Semba, K.; Sukegawa, J.; Miyajima,
N.; Matsubara, K.-I.; Yamamoto, T.; Toyoshima, K.: The yes-related
cellular gene lyn encodes a possible tyrosine kinase similar to p56(lck). Molec.
Cell. Biol. 7: 237-243, 1987.
8. Yoo, S. K.; Starnes, T. W.; Deng, Q.; Huttenlocher, A.: Lyn is
a redox sensor that mediates leukocyte wound attraction in vivo. Nature 480:
109-112, 2011.
*FIELD* CN
Ada Hamosh - updated: 1/4/2012
Paul J. Converse - updated: 3/18/2003
Paul J. Converse - updated: 7/9/2002
Paul J. Converse - updated: 1/17/2002
Paul J. Converse - updated: 12/11/2001
*FIELD* CD
Victor A. McKusick: 9/28/1987
*FIELD* ED
alopez: 01/12/2012
terry: 1/4/2012
mgross: 3/18/2003
alopez: 8/6/2002
mgross: 7/9/2002
mgross: 2/20/2002
mgross: 1/17/2002
mgross: 1/9/2002
terry: 12/11/2001
mark: 3/26/1996
terry: 3/21/1996
mimadm: 4/18/1994
carol: 3/28/1994
supermim: 3/16/1992
supermim: 3/20/1990
carol: 12/13/1989
ddp: 10/27/1989
*RECORD*
*FIELD* NO
165120
*FIELD* TI
*165120 V-YES-1 YAMAGUCHI SARCOMA VIRAL RELATED ONCOGENE HOMOLOG; LYN
;;ONCOGENE LYN
read more*FIELD* TX
CLONING
Using a v-yes DNA as the probe, Yamanashi et al. (1987) screened a human
cDNA library made from placental RNA and derived DNA clones representing
a novel genetic locus termed LYN. Nucleotide sequencing showed that LYN
encodes a novel tyrosine kinase. Northern hybridization analysis showed
that a 3.2-kb LYN mRNA was expressed in a variety of tissues of the
human fetus. The pattern of expression was different from those of
related genes such as YES (164880).
GENE FUNCTION
Parravicini et al. (2002) noted that Lyn deficiency impairs some mast
cell functions, but degranulation and cytokine production are intact. In
Gab2 (606203)-deficient mice, on the other hand, degranulation and
cytokine production are impaired. Using immunoblot analysis, they showed
that although Lyn is essential for Syk (600085) activation and Lat
(602354) phosphorylation after Fcer1 (see FCER1G; 147139) aggregation,
neither Lyn nor Lat are necessary for Gab2 phosphorylation. RT-PCR and
coimmunoprecipitation analyses demonstrated abundant Fyn (137025)
expression in mast cells and an association with Gab2. In cells lacking
Fyn, neither Gab2 nor Akt (164730) were phosphorylated. Functional
analysis showed that Lyn -/- mast cells exhibited hyperdegranulation and
enhanced PI3K (see 601232) activity and Akt phosphorylation, whereas in
Fyn -/- mast cells the degranulation response was inhibited. The
inhibition was associated with decreased binding of PI3K with Gab2.
Parravicini et al. (2002) observed that the degranulation response was
independent of Fcer1 stimulation in Fyn-deficient mast cells and that
degranulation was dependent on PI3K in wildtype and mutant cell lines.
The degranulation response was dependent on a rise in intracellular
calcium that was inhibited in Lyn-deficient mast cells but intact in
Fyn-deficient cells. Degranulation proceeded in Lyn -/- cells due to
increased activation and constitutive phosphorylation of the
calcium-independent protein kinase C delta isoform (PRKCD; 176977).
Parravicini et al. (2002) concluded that Fyn- and Lyn-initiated pathways
synergize in late events at the level of protein kinase C and calcium,
respectively, to regulate mast cell degranulation.
Yoo et al. (2011) identified Lyn as a redox sensor that mediates initial
neutrophil recruitment to wounds in zebrafish larvae. Lyn activation in
neutrophils is dependent on wound-derived H2O2 after tissue injury, and
inhibition of Lyn attenuates neutrophil wound recruitment. Inhibition of
Src family kinase (SFK) also disrupted H2O2-mediated chemotaxis of
primary human neutrophils. In vitro analysis identified a single
cysteine residue, C466, as being responsible for direct
oxidation-mediated activation of Lyn. Furthermore, transgenic
tissue-specific reconstitution with wildtype Lyn and a cysteine mutant
revealed that Lyn C466 is important for the neutrophil wound response
and downstream signaling in vivo. Yoo et al. (2011) concluded that this
was the first identification of a physiologic redox sensor that mediates
leukocyte wound attraction in multicellular organisms.
MAPPING
By hybridization analysis of DNA from sorted chromosomes, Yamanashi et
al. (1987) mapped the LYN gene to chromosome 8q13-qter.
ANIMAL MODEL
Hibbs et al. (1995) demonstrated that mice homozygous for a disruption
of the Lyn locus display abnormalities associated with the B-lymphocyte
lineage and in mast cell function. Despite reduced numbers of
recirculating B lymphocytes, the homozygous deficient mice are
immunoglobulin M hyperglobulinemic. Lyn-deficient mice show IgM
hyperglobulinemia. Immune responses to T-independent and T-dependent
antigens were affected. The deficient mice failed to mediate an allergic
response to IgE cross-linking, indicating that activation of Lyn plays
an indispensable role in signaling by the high-affinity IgE receptor
(FCER). Homozygous deficient mice had circulating autoreactive
antibodies, and many showed severe glomerulonephritis caused by the
deposition of IgG immune complexes in the kidney, a pathology
reminiscent of systemic lupus erythematosus. Hibbs et al. (1995) stated
that, collectively, these results implicated LYN as having an
indispensable role in immunoglobulin-mediated signaling, particularly in
establishing B cell tolerance.
Harder et al. (2001) generated mice with a gain-of-function Lyn mutation
(tyr508 to phe, which they referred to as 'up') analogous to the
tyr527-to-phe activating mutation in the mouse Src gene (190090)
(Webster et al., 1995). Even aging mice with the Lyn up/up phenotype did
not display hematologic malignancies, unlike Lyn -/- mice, which
developed splenomegaly, increased myeloid progenitors, and
monocyte/macrophage tumors. Biochemical analysis revealed that Lyn is
essential in establishing ITIM (immunoreceptor tyrosine-based inhibitory
motif)-dependent signaling and for the activation of specific protein
tyrosine phosphatases within myeloid cells, which may underlie the
susceptibility of Lyn -/- mice to tumorigenesis.
Hasegawa et al. (2001) generated mice deficient in both Cd19 (107265)
and Lyn. Cd19 deficiency suppressed the hyperresponsive phenotype of Lyn
-/- B cells and autoimmunity characterized by serum autoantibodies and
immune complex-mediated glomerulonephritis in Lyn -/- mice. Cd19/Lyn -/-
mice had additional reduction of primitive, predominantly IgM-secreting
B1 lymphocytes. Cd19 deficiency inhibited activation of Src family
protein tyrosine kinase-dependent signaling pathways and delayed
enhanced intracellular calcium responses following B-cell antigen
receptor ligation in Lyn -/- B cells. Hasegawa et al. (2001) concluded
that Cd19 expression is required for the development of autoimmunity in
Lyn -/- mice.
SYK controls pre-B cell development but does not affect NFKB (164011)
induction. Saijo et al. (2003) showed that mice triple-deficient in the
Src family protein tyrosine kinases (SFKs) Blk (191305), Fyn, and Lyn,
but not single-deficient or Syk-deficient mice, had impaired Nfkb
induction and B-cell development. The impairment of Nfkb induction could
be overcome by protein kinase C-lambda (see 176982) activation. Saijo et
al. (2003) suggested that there are 2 separate pathways in pre-B cell
receptor signaling, one SFK-dependent and the other SYK-dependent, that
contribute critically to pre-B cell development.
*FIELD* RF
1. Harder, K. W.; Parsons, L. M.; Armes, J.; Evans, N.; Kountouri,
N.; Clark, R.; Quillici, C.; Grail, D.; Hodgson, G. S.; Dunn, A. R.;
Hibbs, M. L.: Gain- and loss-of-function Lyn mutant mice define a
critical inhibitory role for Lyn in the myeloid lineage. Immunity 15:
603-615, 2001.
2. Hasegawa, M.; Fujimoto, M.; Poe, J. C.; Steeber, D. A.; Lowell,
C. A.; Tedder, T. F.: A CD19-dependent signaling pathway regulates
autoimmunity in Lyn-deficient mice. J. Immun. 167: 2469-2478, 2001.
3. Hibbs, M. L.; Tarlinton, D. M.; Armes, J.; Grail, D.; Hodgson,
G.; Maglitto, R.; Stacker, S. A.; Dunn, A. R.: Multiple defects in
the immune system of Lyn-deficient mice, culminating in autoimmune
disease. Cell 83: 301-311, 1995.
4. Parravicini, V.; Gadina, M.; Kovarova, M.; Odom, S.; Gonzalez-Espinosa,
C.; Furumoto, Y.; Saitoh, S.; Samelson, L. E.; O'Shea, J. J.; Rivera,
J.: Fyn kinase initiates complementary signals required for IgE-dependent
mast cell degranulation. Nature Immun. 3: 741-748, 2002.
5. Saijo, K.; Schmedt, C.; Su, I.; Karasuyama, H.; Lowell, C. A.;
Reth, M.; Adachi, T.; Patke, A.; Santana, A.; Tarakhovsky, A.: Essential
role of Src-family protein tyrosine kinases in NF-kappa-B activation
during B cell development. Nature Immun. 4: 274-279, 2003.
6. Webster, M. A.; Cardiff, R. D.; Muller, W. J.: Induction of mammary
epithelial hyperplasias and mammary tumors in transgenic mice expressing
a murine mammary tumor virus/activated c-src fusion gene. Proc. Nat.
Acad. Sci. 92: 7849-7853, 1995.
7. Yamanashi, Y.; Fukushige, S.-I.; Semba, K.; Sukegawa, J.; Miyajima,
N.; Matsubara, K.-I.; Yamamoto, T.; Toyoshima, K.: The yes-related
cellular gene lyn encodes a possible tyrosine kinase similar to p56(lck). Molec.
Cell. Biol. 7: 237-243, 1987.
8. Yoo, S. K.; Starnes, T. W.; Deng, Q.; Huttenlocher, A.: Lyn is
a redox sensor that mediates leukocyte wound attraction in vivo. Nature 480:
109-112, 2011.
*FIELD* CN
Ada Hamosh - updated: 1/4/2012
Paul J. Converse - updated: 3/18/2003
Paul J. Converse - updated: 7/9/2002
Paul J. Converse - updated: 1/17/2002
Paul J. Converse - updated: 12/11/2001
*FIELD* CD
Victor A. McKusick: 9/28/1987
*FIELD* ED
alopez: 01/12/2012
terry: 1/4/2012
mgross: 3/18/2003
alopez: 8/6/2002
mgross: 7/9/2002
mgross: 2/20/2002
mgross: 1/17/2002
mgross: 1/9/2002
terry: 12/11/2001
mark: 3/26/1996
terry: 3/21/1996
mimadm: 4/18/1994
carol: 3/28/1994
supermim: 3/16/1992
supermim: 3/20/1990
carol: 12/13/1989
ddp: 10/27/1989