Full text data of RPS6KA1
RPS6KA1
(MAPKAPK1A, RSK1)
[Confidence: low (only semi-automatic identification from reviews)]
Ribosomal protein S6 kinase alpha-1; S6K-alpha-1; 2.7.11.1 (90 kDa ribosomal protein S6 kinase 1; p90-RSK 1; p90RSK1; p90S6K; MAP kinase-activated protein kinase 1a; MAPK-activated protein kinase 1a; MAPKAP kinase 1a; MAPKAPK-1a; Ribosomal S6 kinase 1; RSK-1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Ribosomal protein S6 kinase alpha-1; S6K-alpha-1; 2.7.11.1 (90 kDa ribosomal protein S6 kinase 1; p90-RSK 1; p90RSK1; p90S6K; MAP kinase-activated protein kinase 1a; MAPK-activated protein kinase 1a; MAPKAP kinase 1a; MAPKAPK-1a; Ribosomal S6 kinase 1; RSK-1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q15418
ID KS6A1_HUMAN Reviewed; 735 AA.
AC Q15418; A6NGG4; A8K9K7; B2RDY8; B7Z5J0; Q5SVM5; Q5SVM8; Q5SVM9;
read moreAC Q96C05; Q9BQK2;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2002, sequence version 2.
DT 22-JAN-2014, entry version 149.
DE RecName: Full=Ribosomal protein S6 kinase alpha-1;
DE Short=S6K-alpha-1;
DE EC=2.7.11.1;
DE AltName: Full=90 kDa ribosomal protein S6 kinase 1;
DE Short=p90-RSK 1;
DE Short=p90RSK1;
DE Short=p90S6K;
DE AltName: Full=MAP kinase-activated protein kinase 1a;
DE Short=MAPK-activated protein kinase 1a;
DE Short=MAPKAP kinase 1a;
DE Short=MAPKAPK-1a;
DE AltName: Full=Ribosomal S6 kinase 1;
DE Short=RSK-1;
GN Name=RPS6KA1; Synonyms=MAPKAPK1A, RSK1;
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 VARIANT THR-335.
RX PubMed=8141249;
RA Moller D.E., Xia C.-H., Tang W., Zhu A.X., Jakubowski M.;
RT "Human rsk isoforms: cloning and characterization of tissue-specific
RT expression.";
RL Am. J. Physiol. 266:C351-C359(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Testis, and Thyroid;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon;
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 [6]
RP SUBCELLULAR LOCATION.
RX PubMed=9687510; DOI=10.1093/emboj/17.15.4426;
RA Deak M., Clifton A.D., Lucocq J.M., Alessi D.R.;
RT "Mitogen- and stress-activated protein kinase-1 (MSK1) is directly
RT activated by MAPK and SAPK2/p38, and may mediate activation of CREB.";
RL EMBO J. 17:4426-4441(1998).
RN [7]
RP FUNCTION, ENZYME REGULATION, AND PHOSPHORYLATION AT SER-221; THR-359;
RP SER-363; SER-380; THR-573 AND SER-732.
RX PubMed=9430688; DOI=10.1074/jbc.273.3.1496;
RA Dalby K.N., Morrice N., Caudwell F.B., Avruch J., Cohen P.;
RT "Identification of regulatory phosphorylation sites in mitogen-
RT activated protein kinase (MAPK)-activated protein kinase-1a/p90rsk
RT that are inducible by MAPK.";
RL J. Biol. Chem. 273:1496-1505(1998).
RN [8]
RP FUNCTION IN PHOSPHORYLATION OF BAD.
RX PubMed=10679322; DOI=10.1016/S0960-9822(00)00310-9;
RA Shimamura A., Ballif B.A., Richards S.A., Blenis J.;
RT "Rsk1 mediates a MEK-MAP kinase cell survival signal.";
RL Curr. Biol. 10:127-135(2000).
RN [9]
RP FUNCTION IN PHOSPHORYLATION OF CEBPB.
RX PubMed=11684016; DOI=10.1016/S1097-2765(01)00374-4;
RA Buck M., Poli V., Hunter T., Chojkier M.;
RT "C/EBPbeta phosphorylation by RSK creates a functional XEXD caspase
RT inhibitory box critical for cell survival.";
RL Mol. Cell 8:807-816(2001).
RN [10]
RP FUNCTION IN PHOSPHORYLATION OF ETV1/ER81, AND INTERACTION WITH
RP ETV1/ER81.
RX PubMed=12213813; DOI=10.1074/jbc.M205501200;
RA Wu J., Janknecht R.;
RT "Regulation of the ETS transcription factor ER81 by the 90-kDa
RT ribosomal S6 kinase 1 and protein kinase A.";
RL J. Biol. Chem. 277:42669-42679(2002).
RN [11]
RP INTERACTION WITH MAPK1 OR MAPK3.
RX PubMed=12832467; DOI=10.1128/MCB.23.14.4796-4804.2003;
RA Roux P.P., Richards S.A., Blenis J.;
RT "Phosphorylation of p90 ribosomal S6 kinase (RSK) regulates
RT extracellular signal-regulated kinase docking and RSK activity.";
RL Mol. Cell. Biol. 23:4796-4804(2003).
RN [12]
RP FUNCTION, INTERACTION WITH FGFR1, ENZYME REGULATION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=15117958; DOI=10.1074/jbc.M311144200;
RA Hu Y., Fang X., Dunham S.M., Prada C., Stachowiak E.K.,
RA Stachowiak M.K.;
RT "90-kDa ribosomal S6 kinase is a direct target for the nuclear
RT fibroblast growth factor receptor 1 (FGFR1): role in FGFR1
RT signaling.";
RL J. Biol. Chem. 279:29325-29335(2004).
RN [13]
RP FUNCTION IN MTOR SIGNALING, AND INTERACTION WITH TSC2.
RX PubMed=15342917; DOI=10.1073/pnas.0405659101;
RA Roux P.P., Ballif B.A., Anjum R., Gygi S.P., Blenis J.;
RT "Tumor-promoting phorbol esters and activated Ras inactivate the
RT tuberous sclerosis tumor suppressor complex via p90 ribosomal S6
RT kinase.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:13489-13494(2004).
RN [14]
RP FUNCTION IN PHOSPHORYLATION OF DAPK1.
RX PubMed=16213824; DOI=10.1016/j.cub.2005.08.050;
RA Anjum R., Roux P.P., Ballif B.A., Gygi S.P., Blenis J.;
RT "The tumor suppressor DAP kinase is a target of RSK-mediated survival
RT signaling.";
RL Curr. Biol. 15:1762-1767(2005).
RN [15]
RP FUNCTION IN PHOSPHORYLATION OF NR4A1/NUR77.
RX PubMed=16223362; DOI=10.1042/BJ20050967;
RA Wingate A.D., Campbell D.G., Peggie M., Arthur J.S.;
RT "Nur77 is phosphorylated in cells by RSK in response to mitogenic
RT stimulation.";
RL Biochem. J. 393:715-724(2006).
RN [16]
RP FUNCTION IN TRANSLATION REGULATION, AND FUNCTION IN PHOSPHORYLATION OF
RP EIF4B.
RX PubMed=16763566; DOI=10.1038/sj.emboj.7601166;
RA Shahbazian D., Roux P.P., Mieulet V., Cohen M.S., Raught B.,
RA Taunton J., Hershey J.W., Blenis J., Pende M., Sonenberg N.;
RT "The mTOR/PI3K and MAPK pathways converge on eIF4B to control its
RT phosphorylation and activity.";
RL EMBO J. 25:2781-2791(2006).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [18]
RP FUNCTION IN PHOSPHORYLATION OF RPS6.
RX PubMed=17360704; DOI=10.1074/jbc.M700906200;
RA Roux P.P., Shahbazian D., Vu H., Holz M.K., Cohen M.S., Taunton J.,
RA Sonenberg N., Blenis J.;
RT "RAS/ERK signaling promotes site-specific ribosomal protein S6
RT phosphorylation via RSK and stimulates cap-dependent translation.";
RL J. Biol. Chem. 282:14056-14064(2007).
RN [19]
RP FUNCTION IN MTOR SIGNALING.
RX PubMed=18722121; DOI=10.1016/j.cub.2008.07.078;
RA Carriere A., Cargnello M., Julien L.A., Gao H., Bonneil E.,
RA Thibault P., Roux P.P.;
RT "Oncogenic MAPK signaling stimulates mTORC1 activity by promoting RSK-
RT mediated raptor phosphorylation.";
RL Curr. Biol. 18:1269-1277(2008).
RN [20]
RP REVIEW ON FUNCTION, AND REVIEW ON ENZYME REGULATION.
RX PubMed=18508509; DOI=10.2741/3003;
RA Carriere A., Ray H., Blenis J., Roux P.P.;
RT "The RSK factors of activating the Ras/MAPK signaling cascade.";
RL Front. Biosci. 13:4258-4275(2008).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-359; SER-363 AND
RP SER-380, 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 [22]
RP REVIEW ON FUNCTION, AND REVIEW ON ENZYME REGULATION.
RX PubMed=18813292; DOI=10.1038/nrm2509;
RA Anjum R., Blenis J.;
RT "The RSK family of kinases: emerging roles in cellular signalling.";
RL Nat. Rev. Mol. Cell Biol. 9:747-758(2008).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-359; SER-363; SER-369
RP AND SER-380, AND MASS SPECTROMETRY.
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 [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-54; SER-307; THR-359;
RP SER-363; SER-369 AND SER-380, 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 [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-380, 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 [26]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-359 AND SER-363, AND
RP MASS 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 [28]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 33-353 IN COMPLEX WITH
RP INHIBITOR.
RX PubMed=17965187; DOI=10.1110/ps.073123707;
RA Ikuta M., Kornienko M., Byrne N., Reid J.C., Mizuarai S., Kotani H.,
RA Munshi S.K.;
RT "Crystal structures of the N-terminal kinase domain of human RSK1
RT bound to three different ligands: Implications for the design of RSK1
RT specific inhibitors.";
RL Protein Sci. 16:2626-2635(2007).
RN [29]
RP VARIANT [LARGE SCALE ANALYSIS] THR-335.
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: Serine/threonine-protein kinase that acts downstream of
CC ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic
CC and stress-induced activation of the transcription factors CREB1,
CC ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and
CC EIF4B phosphorylation, and mediates cellular proliferation,
CC survival, and differentiation by modulating mTOR signaling and
CC repressing pro-apoptotic function of BAD and DAPK1. In fibroblast,
CC is required for EGF-stimulated phosphorylation of CREB1, which
CC results in the subsequent transcriptional activation of several
CC immediate-early genes. In response to mitogenic stimulation (EGF
CC and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81
CC transcription factors and the cofactor CREBBP. Upon insulin-
CC derived signal, acts indirectly on the transcription regulation of
CC several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting
CC its activity. Phosphorylates RPS6 in response to serum or EGF via
CC an mTOR-independent mechanism and promotes translation initiation
CC by facilitating assembly of the preinitiation complex. In response
CC to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the
CC EIF3 complex and stimulating cap-dependent translation. Is
CC involved in the mTOR nutrient-sensing pathway by directly
CC phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2
CC ability to suppress mTOR signaling, and mediates phosphorylation
CC of RPTOR, which regulates mTORC1 activity and may promote
CC rapamycin-sensitive signaling independently of the PI3K/AKT
CC pathway. Mediates cell survival by phosphorylating the pro-
CC apoptotic proteins BAD and DAPK1 and suppressing their pro-
CC apoptotic function. Promotes the survival of hepatic stellate
CC cells by phosphorylating CEBPB in response to the hepatotoxin
CC carbon tetrachloride (CCl4). Is involved in cell cycle regulation
CC by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B
CC association with 14-3-3 proteins and prevents its translocation to
CC the nucleus and inhibition of G1 progression.
CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
CC -!- COFACTOR: Magnesium.
CC -!- ENZYME REGULATION: Upon extracellular signal or mitogen
CC stimulation, phosphorylated at Thr-573 in the C-terminal kinase
CC domain (CTKD) by MAPK1/ERK2 and MAPK3/ERK1. The activated CTKD
CC then autophosphorylates Ser-380, allowing binding of PDPK1, which
CC in turn phosphorylates Ser-221 in the N-terminal kinase domain
CC (NTDK) leading to the full activation of the protein and
CC subsequent phosphorylation of the substrates by the NTKD.
CC -!- SUBUNIT: Forms a complex with either MAPK1/ERK2 or MAPK3/ERK1 in
CC quiescent cells. Transiently dissociates following mitogenic
CC stimulation. Interacts with ETV1/ER81 and FGFR1.
CC -!- INTERACTION:
CC P08238:HSP90AB1; NbExp=2; IntAct=EBI-963034, EBI-352572;
CC P50552:VASP; NbExp=4; IntAct=EBI-963034, EBI-748201;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q15418-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q15418-2; Sequence=VSP_041380;
CC Name=3;
CC IsoId=Q15418-3; Sequence=VSP_041580;
CC Note=No experimental confirmation available;
CC -!- PTM: Activated by phosphorylation at Ser-221 by PDPK1.
CC Autophosphorylated on Ser-380, as part of the activation process.
CC May be phosphorylated at Thr-359 and Ser-363 by MAPK1/ERK2 and
CC MAPK3/ERK1.
CC -!- PTM: N-terminal myristoylation results in an activated kinase in
CC the absence of added growth factors.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. S6 kinase subfamily.
CC -!- SIMILARITY: Contains 1 AGC-kinase C-terminal domain.
CC -!- SIMILARITY: Contains 2 protein kinase domains.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/RPS6KA1ID43477ch1p36.html";
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DR EMBL; L07597; AAC82497.1; -; mRNA.
DR EMBL; AK292722; BAF85411.1; -; mRNA.
DR EMBL; AK299007; BAH12926.1; -; mRNA.
DR EMBL; AK315730; BAG38085.1; -; mRNA.
DR EMBL; AL109743; CAC36348.1; -; Genomic_DNA.
DR EMBL; AL627313; CAI14647.1; -; Genomic_DNA.
DR EMBL; AL627313; CAI14648.1; -; Genomic_DNA.
DR EMBL; AL627313; CAI14649.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX07799.1; -; Genomic_DNA.
DR EMBL; BC014966; AAH14966.1; -; mRNA.
DR PIR; I51901; I51901.
DR RefSeq; NP_001006666.1; NM_001006665.1.
DR RefSeq; NP_002944.2; NM_002953.3.
DR RefSeq; XP_005246024.1; XM_005245967.1.
DR UniGene; Hs.149957; -.
DR PDB; 2WNT; X-ray; 2.40 A; A/B=413-719.
DR PDB; 2Z7Q; X-ray; 2.00 A; A=33-353.
DR PDB; 2Z7R; X-ray; 2.00 A; A=33-353.
DR PDB; 2Z7S; X-ray; 2.10 A; A=33-353.
DR PDB; 3RNY; X-ray; 2.70 A; A/B=411-735.
DR PDB; 3TEI; X-ray; 2.40 A; B=712-735.
DR PDB; 4H3P; X-ray; 2.30 A; B/E=712-735.
DR PDBsum; 2WNT; -.
DR PDBsum; 2Z7Q; -.
DR PDBsum; 2Z7R; -.
DR PDBsum; 2Z7S; -.
DR PDBsum; 3RNY; -.
DR PDBsum; 3TEI; -.
DR PDBsum; 4H3P; -.
DR ProteinModelPortal; Q15418; -.
DR SMR; Q15418; 53-709.
DR DIP; DIP-29987N; -.
DR IntAct; Q15418; 28.
DR MINT; MINT-207205; -.
DR STRING; 9606.ENSP00000363277; -.
DR BindingDB; Q15418; -.
DR ChEMBL; CHEMBL2553; -.
DR GuidetoPHARMACOLOGY; 1527; -.
DR PhosphoSite; Q15418; -.
DR DMDM; 20178306; -.
DR UCD-2DPAGE; Q15418; -.
DR PaxDb; Q15418; -.
DR PRIDE; Q15418; -.
DR DNASU; 6195; -.
DR Ensembl; ENST00000374162; ENSP00000363277; ENSG00000117676.
DR Ensembl; ENST00000374168; ENSP00000363283; ENSG00000117676.
DR Ensembl; ENST00000526792; ENSP00000431651; ENSG00000117676.
DR Ensembl; ENST00000531382; ENSP00000435412; ENSG00000117676.
DR GeneID; 6195; -.
DR KEGG; hsa:6195; -.
DR UCSC; uc001bmr.1; human.
DR CTD; 6195; -.
DR GeneCards; GC01P026856; -.
DR HGNC; HGNC:10430; RPS6KA1.
DR HPA; CAB003852; -.
DR HPA; HPA007981; -.
DR MIM; 601684; gene.
DR neXtProt; NX_Q15418; -.
DR PharmGKB; PA34845; -.
DR eggNOG; COG0515; -.
DR HOVERGEN; HBG108317; -.
DR KO; K04373; -.
DR OMA; PWITQKD; -.
DR OrthoDB; EOG7B8S38; -.
DR PhylomeDB; Q15418; -.
DR BRENDA; 2.7.11.1; 2681.
DR Reactome; REACT_111045; Developmental Biology.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_120956; Cellular responses to stress.
DR Reactome; REACT_13685; Neuronal System.
DR Reactome; REACT_6782; TRAF6 Mediated Induction of proinflammatory cytokines.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; Q15418; -.
DR ChiTaRS; RPS6KA1; human.
DR EvolutionaryTrace; Q15418; -.
DR GeneWiki; RPS6KA1; -.
DR GenomeRNAi; 6195; -.
DR NextBio; 24057; -.
DR PRO; PR:Q15418; -.
DR ArrayExpress; Q15418; -.
DR Bgee; Q15418; -.
DR CleanEx; HS_RPS6KA1; -.
DR Genevestigator; Q15418; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005819; C:spindle; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0043027; F:cysteine-type endopeptidase inhibitor activity involved in apoptotic process; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0007411; P:axon guidance; TAS:Reactome.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; TAS:Reactome.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
DR GO; GO:0045597; P:positive regulation of cell differentiation; TAS:UniProtKB.
DR GO; GO:0030307; P:positive regulation of cell growth; TAS:UniProtKB.
DR GO; GO:2000491; P:positive regulation of hepatic stellate cell activation; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IMP:BHF-UCL.
DR GO; GO:0043620; P:regulation of DNA-dependent transcription in response to stress; TAS:UniProtKB.
DR GO; GO:0043555; P:regulation of translation in response to stress; TAS:UniProtKB.
DR GO; GO:0051403; P:stress-activated MAPK cascade; TAS:Reactome.
DR GO; GO:0007268; P:synaptic transmission; TAS:Reactome.
DR GO; GO:0034166; P:toll-like receptor 10 signaling pathway; TAS:Reactome.
DR GO; GO:0034134; P:toll-like receptor 2 signaling pathway; TAS:Reactome.
DR GO; GO:0034138; P:toll-like receptor 3 signaling pathway; TAS:Reactome.
DR GO; GO:0034142; P:toll-like receptor 4 signaling pathway; TAS:Reactome.
DR GO; GO:0034146; P:toll-like receptor 5 signaling pathway; TAS:Reactome.
DR GO; GO:0034162; P:toll-like receptor 9 signaling pathway; TAS:Reactome.
DR GO; GO:0038123; P:toll-like receptor TLR1:TLR2 signaling pathway; TAS:Reactome.
DR GO; GO:0038124; P:toll-like receptor TLR6:TLR2 signaling pathway; TAS:Reactome.
DR GO; GO:0035666; P:TRIF-dependent toll-like receptor signaling pathway; TAS:Reactome.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR011009; Kinase-like_dom.
DR InterPro; IPR017892; Pkinase_C.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR016239; Ribosomal_S6_kinase_II.
DR InterPro; IPR002290; Ser/Thr_dual-sp_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 2.
DR Pfam; PF00433; Pkinase_C; 1.
DR PIRSF; PIRSF000606; Ribsml_S6_kin_2; 1.
DR SMART; SM00133; S_TK_X; 1.
DR SMART; SM00220; S_TKc; 2.
DR SUPFAM; SSF56112; SSF56112; 2.
DR PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 2.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 2.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Cell cycle;
KW Complete proteome; Cytoplasm; Kinase; Magnesium; Metal-binding;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism;
KW Reference proteome; Repeat; Serine/threonine-protein kinase;
KW Stress response; Transferase.
FT CHAIN 1 735 Ribosomal protein S6 kinase alpha-1.
FT /FTId=PRO_0000086198.
FT DOMAIN 62 321 Protein kinase 1.
FT DOMAIN 322 391 AGC-kinase C-terminal.
FT DOMAIN 418 675 Protein kinase 2.
FT NP_BIND 68 76 ATP (By similarity).
FT NP_BIND 424 432 ATP (By similarity).
FT ACT_SITE 187 187 Proton acceptor (By similarity).
FT ACT_SITE 535 535 Proton acceptor (By similarity).
FT BINDING 94 94 ATP (By similarity).
FT BINDING 447 447 ATP (By similarity).
FT MOD_RES 54 54 Phosphoserine.
FT MOD_RES 221 221 Phosphoserine; by PDPK1 (Probable).
FT MOD_RES 307 307 Phosphoserine.
FT MOD_RES 348 348 Phosphothreonine.
FT MOD_RES 359 359 Phosphothreonine.
FT MOD_RES 363 363 Phosphoserine.
FT MOD_RES 369 369 Phosphoserine.
FT MOD_RES 380 380 Phosphoserine; by autocatalysis.
FT MOD_RES 573 573 Phosphothreonine.
FT MOD_RES 732 732 Phosphoserine.
FT VAR_SEQ 1 92 Missing (in isoform 3).
FT /FTId=VSP_041580.
FT VAR_SEQ 1 36 MPLAQLKEPWPLMELVPLDPENGQTSGEEAGLQPSK -> M
FT EQDPKPPRLRLWALIPWLPRKQRPRISQTSLPVPGPGSGPQ
FT RDS (in isoform 2).
FT /FTId=VSP_041380.
FT VARIANT 335 335 K -> T (in dbSNP:rs2229712).
FT /FTId=VAR_021864.
FT CONFLICT 609 609 A -> T (in Ref. 2; BAF85411).
FT CONFLICT 619 619 S -> G (in Ref. 2; BAF85411).
FT HELIX 59 61
FT STRAND 62 71
FT STRAND 74 81
FT STRAND 83 86
FT STRAND 90 96
FT STRAND 127 133
FT STRAND 136 141
FT HELIX 149 156
FT HELIX 161 180
FT HELIX 190 192
FT STRAND 193 195
FT STRAND 197 199
FT STRAND 201 203
FT HELIX 226 228
FT HELIX 231 234
FT HELIX 241 257
FT HELIX 267 276
FT HELIX 287 296
FT TURN 301 303
FT STRAND 307 310
FT HELIX 312 316
FT HELIX 319 321
FT HELIX 326 330
FT STRAND 418 427
FT STRAND 430 437
FT TURN 438 440
FT STRAND 443 450
FT HELIX 457 466
FT STRAND 475 480
FT STRAND 482 489
FT HELIX 497 502
FT STRAND 503 505
FT HELIX 509 528
FT HELIX 538 540
FT STRAND 541 545
FT HELIX 550 552
FT STRAND 553 555
FT TURN 574 576
FT HELIX 588 609
FT HELIX 622 631
FT HELIX 639 643
FT HELIX 646 655
FT HELIX 660 662
FT HELIX 666 670
FT HELIX 673 676
FT HELIX 678 680
FT HELIX 691 707
FT HELIX 717 719
FT HELIX 721 724
SQ SEQUENCE 735 AA; 82723 MW; 765731A4442A53DF CRC64;
MPLAQLKEPW PLMELVPLDP ENGQTSGEEA GLQPSKDEGV LKEISITHHV KAGSEKADPS
HFELLKVLGQ GSFGKVFLVR KVTRPDSGHL YAMKVLKKAT LKVRDRVRTK MERDILADVN
HPFVVKLHYA FQTEGKLYLI LDFLRGGDLF TRLSKEVMFT EEDVKFYLAE LALGLDHLHS
LGIIYRDLKP ENILLDEEGH IKLTDFGLSK EAIDHEKKAY SFCGTVEYMA PEVVNRQGHS
HSADWWSYGV LMFEMLTGSL PFQGKDRKET MTLILKAKLG MPQFLSTEAQ SLLRALFKRN
PANRLGSGPD GAEEIKRHVF YSTIDWNKLY RREIKPPFKP AVAQPDDTFY FDTEFTSRTP
KDSPGIPPSA GAHQLFRGFS FVATGLMEDD GKPRAPQAPL HSVVQQLHGK NLVFSDGYVV
KETIGVGSYS ECKRCVHKAT NMEYAVKVID KSKRDPSEEI EILLRYGQHP NIITLKDVYD
DGKHVYLVTE LMRGGELLDK ILRQKFFSER EASFVLHTIG KTVEYLHSQG VVHRDLKPSN
ILYVDESGNP ECLRICDFGF AKQLRAENGL LMTPCYTANF VAPEVLKRQG YDEGCDIWSL
GILLYTMLAG YTPFANGPSD TPEEILTRIG SGKFTLSGGN WNTVSETAKD LVSKMLHVDP
HQRLTAKQVL QHPWVTQKDK LPQSQLSHQD LQLVKGAMAA TYSALNSSKP TPQLKPIESS
ILAQRRVRKL PSTTL
//
ID KS6A1_HUMAN Reviewed; 735 AA.
AC Q15418; A6NGG4; A8K9K7; B2RDY8; B7Z5J0; Q5SVM5; Q5SVM8; Q5SVM9;
read moreAC Q96C05; Q9BQK2;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2002, sequence version 2.
DT 22-JAN-2014, entry version 149.
DE RecName: Full=Ribosomal protein S6 kinase alpha-1;
DE Short=S6K-alpha-1;
DE EC=2.7.11.1;
DE AltName: Full=90 kDa ribosomal protein S6 kinase 1;
DE Short=p90-RSK 1;
DE Short=p90RSK1;
DE Short=p90S6K;
DE AltName: Full=MAP kinase-activated protein kinase 1a;
DE Short=MAPK-activated protein kinase 1a;
DE Short=MAPKAP kinase 1a;
DE Short=MAPKAPK-1a;
DE AltName: Full=Ribosomal S6 kinase 1;
DE Short=RSK-1;
GN Name=RPS6KA1; Synonyms=MAPKAPK1A, RSK1;
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 VARIANT THR-335.
RX PubMed=8141249;
RA Moller D.E., Xia C.-H., Tang W., Zhu A.X., Jakubowski M.;
RT "Human rsk isoforms: cloning and characterization of tissue-specific
RT expression.";
RL Am. J. Physiol. 266:C351-C359(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Testis, and Thyroid;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon;
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 [6]
RP SUBCELLULAR LOCATION.
RX PubMed=9687510; DOI=10.1093/emboj/17.15.4426;
RA Deak M., Clifton A.D., Lucocq J.M., Alessi D.R.;
RT "Mitogen- and stress-activated protein kinase-1 (MSK1) is directly
RT activated by MAPK and SAPK2/p38, and may mediate activation of CREB.";
RL EMBO J. 17:4426-4441(1998).
RN [7]
RP FUNCTION, ENZYME REGULATION, AND PHOSPHORYLATION AT SER-221; THR-359;
RP SER-363; SER-380; THR-573 AND SER-732.
RX PubMed=9430688; DOI=10.1074/jbc.273.3.1496;
RA Dalby K.N., Morrice N., Caudwell F.B., Avruch J., Cohen P.;
RT "Identification of regulatory phosphorylation sites in mitogen-
RT activated protein kinase (MAPK)-activated protein kinase-1a/p90rsk
RT that are inducible by MAPK.";
RL J. Biol. Chem. 273:1496-1505(1998).
RN [8]
RP FUNCTION IN PHOSPHORYLATION OF BAD.
RX PubMed=10679322; DOI=10.1016/S0960-9822(00)00310-9;
RA Shimamura A., Ballif B.A., Richards S.A., Blenis J.;
RT "Rsk1 mediates a MEK-MAP kinase cell survival signal.";
RL Curr. Biol. 10:127-135(2000).
RN [9]
RP FUNCTION IN PHOSPHORYLATION OF CEBPB.
RX PubMed=11684016; DOI=10.1016/S1097-2765(01)00374-4;
RA Buck M., Poli V., Hunter T., Chojkier M.;
RT "C/EBPbeta phosphorylation by RSK creates a functional XEXD caspase
RT inhibitory box critical for cell survival.";
RL Mol. Cell 8:807-816(2001).
RN [10]
RP FUNCTION IN PHOSPHORYLATION OF ETV1/ER81, AND INTERACTION WITH
RP ETV1/ER81.
RX PubMed=12213813; DOI=10.1074/jbc.M205501200;
RA Wu J., Janknecht R.;
RT "Regulation of the ETS transcription factor ER81 by the 90-kDa
RT ribosomal S6 kinase 1 and protein kinase A.";
RL J. Biol. Chem. 277:42669-42679(2002).
RN [11]
RP INTERACTION WITH MAPK1 OR MAPK3.
RX PubMed=12832467; DOI=10.1128/MCB.23.14.4796-4804.2003;
RA Roux P.P., Richards S.A., Blenis J.;
RT "Phosphorylation of p90 ribosomal S6 kinase (RSK) regulates
RT extracellular signal-regulated kinase docking and RSK activity.";
RL Mol. Cell. Biol. 23:4796-4804(2003).
RN [12]
RP FUNCTION, INTERACTION WITH FGFR1, ENZYME REGULATION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=15117958; DOI=10.1074/jbc.M311144200;
RA Hu Y., Fang X., Dunham S.M., Prada C., Stachowiak E.K.,
RA Stachowiak M.K.;
RT "90-kDa ribosomal S6 kinase is a direct target for the nuclear
RT fibroblast growth factor receptor 1 (FGFR1): role in FGFR1
RT signaling.";
RL J. Biol. Chem. 279:29325-29335(2004).
RN [13]
RP FUNCTION IN MTOR SIGNALING, AND INTERACTION WITH TSC2.
RX PubMed=15342917; DOI=10.1073/pnas.0405659101;
RA Roux P.P., Ballif B.A., Anjum R., Gygi S.P., Blenis J.;
RT "Tumor-promoting phorbol esters and activated Ras inactivate the
RT tuberous sclerosis tumor suppressor complex via p90 ribosomal S6
RT kinase.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:13489-13494(2004).
RN [14]
RP FUNCTION IN PHOSPHORYLATION OF DAPK1.
RX PubMed=16213824; DOI=10.1016/j.cub.2005.08.050;
RA Anjum R., Roux P.P., Ballif B.A., Gygi S.P., Blenis J.;
RT "The tumor suppressor DAP kinase is a target of RSK-mediated survival
RT signaling.";
RL Curr. Biol. 15:1762-1767(2005).
RN [15]
RP FUNCTION IN PHOSPHORYLATION OF NR4A1/NUR77.
RX PubMed=16223362; DOI=10.1042/BJ20050967;
RA Wingate A.D., Campbell D.G., Peggie M., Arthur J.S.;
RT "Nur77 is phosphorylated in cells by RSK in response to mitogenic
RT stimulation.";
RL Biochem. J. 393:715-724(2006).
RN [16]
RP FUNCTION IN TRANSLATION REGULATION, AND FUNCTION IN PHOSPHORYLATION OF
RP EIF4B.
RX PubMed=16763566; DOI=10.1038/sj.emboj.7601166;
RA Shahbazian D., Roux P.P., Mieulet V., Cohen M.S., Raught B.,
RA Taunton J., Hershey J.W., Blenis J., Pende M., Sonenberg N.;
RT "The mTOR/PI3K and MAPK pathways converge on eIF4B to control its
RT phosphorylation and activity.";
RL EMBO J. 25:2781-2791(2006).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [18]
RP FUNCTION IN PHOSPHORYLATION OF RPS6.
RX PubMed=17360704; DOI=10.1074/jbc.M700906200;
RA Roux P.P., Shahbazian D., Vu H., Holz M.K., Cohen M.S., Taunton J.,
RA Sonenberg N., Blenis J.;
RT "RAS/ERK signaling promotes site-specific ribosomal protein S6
RT phosphorylation via RSK and stimulates cap-dependent translation.";
RL J. Biol. Chem. 282:14056-14064(2007).
RN [19]
RP FUNCTION IN MTOR SIGNALING.
RX PubMed=18722121; DOI=10.1016/j.cub.2008.07.078;
RA Carriere A., Cargnello M., Julien L.A., Gao H., Bonneil E.,
RA Thibault P., Roux P.P.;
RT "Oncogenic MAPK signaling stimulates mTORC1 activity by promoting RSK-
RT mediated raptor phosphorylation.";
RL Curr. Biol. 18:1269-1277(2008).
RN [20]
RP REVIEW ON FUNCTION, AND REVIEW ON ENZYME REGULATION.
RX PubMed=18508509; DOI=10.2741/3003;
RA Carriere A., Ray H., Blenis J., Roux P.P.;
RT "The RSK factors of activating the Ras/MAPK signaling cascade.";
RL Front. Biosci. 13:4258-4275(2008).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-359; SER-363 AND
RP SER-380, 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 [22]
RP REVIEW ON FUNCTION, AND REVIEW ON ENZYME REGULATION.
RX PubMed=18813292; DOI=10.1038/nrm2509;
RA Anjum R., Blenis J.;
RT "The RSK family of kinases: emerging roles in cellular signalling.";
RL Nat. Rev. Mol. Cell Biol. 9:747-758(2008).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-359; SER-363; SER-369
RP AND SER-380, AND MASS SPECTROMETRY.
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 [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-54; SER-307; THR-359;
RP SER-363; SER-369 AND SER-380, 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 [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-380, 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 [26]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-359 AND SER-363, AND
RP MASS 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 [28]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 33-353 IN COMPLEX WITH
RP INHIBITOR.
RX PubMed=17965187; DOI=10.1110/ps.073123707;
RA Ikuta M., Kornienko M., Byrne N., Reid J.C., Mizuarai S., Kotani H.,
RA Munshi S.K.;
RT "Crystal structures of the N-terminal kinase domain of human RSK1
RT bound to three different ligands: Implications for the design of RSK1
RT specific inhibitors.";
RL Protein Sci. 16:2626-2635(2007).
RN [29]
RP VARIANT [LARGE SCALE ANALYSIS] THR-335.
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: Serine/threonine-protein kinase that acts downstream of
CC ERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic
CC and stress-induced activation of the transcription factors CREB1,
CC ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and
CC EIF4B phosphorylation, and mediates cellular proliferation,
CC survival, and differentiation by modulating mTOR signaling and
CC repressing pro-apoptotic function of BAD and DAPK1. In fibroblast,
CC is required for EGF-stimulated phosphorylation of CREB1, which
CC results in the subsequent transcriptional activation of several
CC immediate-early genes. In response to mitogenic stimulation (EGF
CC and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81
CC transcription factors and the cofactor CREBBP. Upon insulin-
CC derived signal, acts indirectly on the transcription regulation of
CC several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting
CC its activity. Phosphorylates RPS6 in response to serum or EGF via
CC an mTOR-independent mechanism and promotes translation initiation
CC by facilitating assembly of the preinitiation complex. In response
CC to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the
CC EIF3 complex and stimulating cap-dependent translation. Is
CC involved in the mTOR nutrient-sensing pathway by directly
CC phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2
CC ability to suppress mTOR signaling, and mediates phosphorylation
CC of RPTOR, which regulates mTORC1 activity and may promote
CC rapamycin-sensitive signaling independently of the PI3K/AKT
CC pathway. Mediates cell survival by phosphorylating the pro-
CC apoptotic proteins BAD and DAPK1 and suppressing their pro-
CC apoptotic function. Promotes the survival of hepatic stellate
CC cells by phosphorylating CEBPB in response to the hepatotoxin
CC carbon tetrachloride (CCl4). Is involved in cell cycle regulation
CC by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B
CC association with 14-3-3 proteins and prevents its translocation to
CC the nucleus and inhibition of G1 progression.
CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
CC -!- COFACTOR: Magnesium.
CC -!- ENZYME REGULATION: Upon extracellular signal or mitogen
CC stimulation, phosphorylated at Thr-573 in the C-terminal kinase
CC domain (CTKD) by MAPK1/ERK2 and MAPK3/ERK1. The activated CTKD
CC then autophosphorylates Ser-380, allowing binding of PDPK1, which
CC in turn phosphorylates Ser-221 in the N-terminal kinase domain
CC (NTDK) leading to the full activation of the protein and
CC subsequent phosphorylation of the substrates by the NTKD.
CC -!- SUBUNIT: Forms a complex with either MAPK1/ERK2 or MAPK3/ERK1 in
CC quiescent cells. Transiently dissociates following mitogenic
CC stimulation. Interacts with ETV1/ER81 and FGFR1.
CC -!- INTERACTION:
CC P08238:HSP90AB1; NbExp=2; IntAct=EBI-963034, EBI-352572;
CC P50552:VASP; NbExp=4; IntAct=EBI-963034, EBI-748201;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q15418-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q15418-2; Sequence=VSP_041380;
CC Name=3;
CC IsoId=Q15418-3; Sequence=VSP_041580;
CC Note=No experimental confirmation available;
CC -!- PTM: Activated by phosphorylation at Ser-221 by PDPK1.
CC Autophosphorylated on Ser-380, as part of the activation process.
CC May be phosphorylated at Thr-359 and Ser-363 by MAPK1/ERK2 and
CC MAPK3/ERK1.
CC -!- PTM: N-terminal myristoylation results in an activated kinase in
CC the absence of added growth factors.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. S6 kinase subfamily.
CC -!- SIMILARITY: Contains 1 AGC-kinase C-terminal domain.
CC -!- SIMILARITY: Contains 2 protein kinase domains.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/RPS6KA1ID43477ch1p36.html";
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DR EMBL; L07597; AAC82497.1; -; mRNA.
DR EMBL; AK292722; BAF85411.1; -; mRNA.
DR EMBL; AK299007; BAH12926.1; -; mRNA.
DR EMBL; AK315730; BAG38085.1; -; mRNA.
DR EMBL; AL109743; CAC36348.1; -; Genomic_DNA.
DR EMBL; AL627313; CAI14647.1; -; Genomic_DNA.
DR EMBL; AL627313; CAI14648.1; -; Genomic_DNA.
DR EMBL; AL627313; CAI14649.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX07799.1; -; Genomic_DNA.
DR EMBL; BC014966; AAH14966.1; -; mRNA.
DR PIR; I51901; I51901.
DR RefSeq; NP_001006666.1; NM_001006665.1.
DR RefSeq; NP_002944.2; NM_002953.3.
DR RefSeq; XP_005246024.1; XM_005245967.1.
DR UniGene; Hs.149957; -.
DR PDB; 2WNT; X-ray; 2.40 A; A/B=413-719.
DR PDB; 2Z7Q; X-ray; 2.00 A; A=33-353.
DR PDB; 2Z7R; X-ray; 2.00 A; A=33-353.
DR PDB; 2Z7S; X-ray; 2.10 A; A=33-353.
DR PDB; 3RNY; X-ray; 2.70 A; A/B=411-735.
DR PDB; 3TEI; X-ray; 2.40 A; B=712-735.
DR PDB; 4H3P; X-ray; 2.30 A; B/E=712-735.
DR PDBsum; 2WNT; -.
DR PDBsum; 2Z7Q; -.
DR PDBsum; 2Z7R; -.
DR PDBsum; 2Z7S; -.
DR PDBsum; 3RNY; -.
DR PDBsum; 3TEI; -.
DR PDBsum; 4H3P; -.
DR ProteinModelPortal; Q15418; -.
DR SMR; Q15418; 53-709.
DR DIP; DIP-29987N; -.
DR IntAct; Q15418; 28.
DR MINT; MINT-207205; -.
DR STRING; 9606.ENSP00000363277; -.
DR BindingDB; Q15418; -.
DR ChEMBL; CHEMBL2553; -.
DR GuidetoPHARMACOLOGY; 1527; -.
DR PhosphoSite; Q15418; -.
DR DMDM; 20178306; -.
DR UCD-2DPAGE; Q15418; -.
DR PaxDb; Q15418; -.
DR PRIDE; Q15418; -.
DR DNASU; 6195; -.
DR Ensembl; ENST00000374162; ENSP00000363277; ENSG00000117676.
DR Ensembl; ENST00000374168; ENSP00000363283; ENSG00000117676.
DR Ensembl; ENST00000526792; ENSP00000431651; ENSG00000117676.
DR Ensembl; ENST00000531382; ENSP00000435412; ENSG00000117676.
DR GeneID; 6195; -.
DR KEGG; hsa:6195; -.
DR UCSC; uc001bmr.1; human.
DR CTD; 6195; -.
DR GeneCards; GC01P026856; -.
DR HGNC; HGNC:10430; RPS6KA1.
DR HPA; CAB003852; -.
DR HPA; HPA007981; -.
DR MIM; 601684; gene.
DR neXtProt; NX_Q15418; -.
DR PharmGKB; PA34845; -.
DR eggNOG; COG0515; -.
DR HOVERGEN; HBG108317; -.
DR KO; K04373; -.
DR OMA; PWITQKD; -.
DR OrthoDB; EOG7B8S38; -.
DR PhylomeDB; Q15418; -.
DR BRENDA; 2.7.11.1; 2681.
DR Reactome; REACT_111045; Developmental Biology.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_120956; Cellular responses to stress.
DR Reactome; REACT_13685; Neuronal System.
DR Reactome; REACT_6782; TRAF6 Mediated Induction of proinflammatory cytokines.
DR Reactome; REACT_6900; Immune System.
DR SignaLink; Q15418; -.
DR ChiTaRS; RPS6KA1; human.
DR EvolutionaryTrace; Q15418; -.
DR GeneWiki; RPS6KA1; -.
DR GenomeRNAi; 6195; -.
DR NextBio; 24057; -.
DR PRO; PR:Q15418; -.
DR ArrayExpress; Q15418; -.
DR Bgee; Q15418; -.
DR CleanEx; HS_RPS6KA1; -.
DR Genevestigator; Q15418; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005819; C:spindle; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0043027; F:cysteine-type endopeptidase inhibitor activity involved in apoptotic process; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0007411; P:axon guidance; TAS:Reactome.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; TAS:Reactome.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
DR GO; GO:0045597; P:positive regulation of cell differentiation; TAS:UniProtKB.
DR GO; GO:0030307; P:positive regulation of cell growth; TAS:UniProtKB.
DR GO; GO:2000491; P:positive regulation of hepatic stellate cell activation; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IMP:BHF-UCL.
DR GO; GO:0043620; P:regulation of DNA-dependent transcription in response to stress; TAS:UniProtKB.
DR GO; GO:0043555; P:regulation of translation in response to stress; TAS:UniProtKB.
DR GO; GO:0051403; P:stress-activated MAPK cascade; TAS:Reactome.
DR GO; GO:0007268; P:synaptic transmission; TAS:Reactome.
DR GO; GO:0034166; P:toll-like receptor 10 signaling pathway; TAS:Reactome.
DR GO; GO:0034134; P:toll-like receptor 2 signaling pathway; TAS:Reactome.
DR GO; GO:0034138; P:toll-like receptor 3 signaling pathway; TAS:Reactome.
DR GO; GO:0034142; P:toll-like receptor 4 signaling pathway; TAS:Reactome.
DR GO; GO:0034146; P:toll-like receptor 5 signaling pathway; TAS:Reactome.
DR GO; GO:0034162; P:toll-like receptor 9 signaling pathway; TAS:Reactome.
DR GO; GO:0038123; P:toll-like receptor TLR1:TLR2 signaling pathway; TAS:Reactome.
DR GO; GO:0038124; P:toll-like receptor TLR6:TLR2 signaling pathway; TAS:Reactome.
DR GO; GO:0035666; P:TRIF-dependent toll-like receptor signaling pathway; TAS:Reactome.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR011009; Kinase-like_dom.
DR InterPro; IPR017892; Pkinase_C.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR016239; Ribosomal_S6_kinase_II.
DR InterPro; IPR002290; Ser/Thr_dual-sp_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 2.
DR Pfam; PF00433; Pkinase_C; 1.
DR PIRSF; PIRSF000606; Ribsml_S6_kin_2; 1.
DR SMART; SM00133; S_TK_X; 1.
DR SMART; SM00220; S_TKc; 2.
DR SUPFAM; SSF56112; SSF56112; 2.
DR PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 2.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 2.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Cell cycle;
KW Complete proteome; Cytoplasm; Kinase; Magnesium; Metal-binding;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism;
KW Reference proteome; Repeat; Serine/threonine-protein kinase;
KW Stress response; Transferase.
FT CHAIN 1 735 Ribosomal protein S6 kinase alpha-1.
FT /FTId=PRO_0000086198.
FT DOMAIN 62 321 Protein kinase 1.
FT DOMAIN 322 391 AGC-kinase C-terminal.
FT DOMAIN 418 675 Protein kinase 2.
FT NP_BIND 68 76 ATP (By similarity).
FT NP_BIND 424 432 ATP (By similarity).
FT ACT_SITE 187 187 Proton acceptor (By similarity).
FT ACT_SITE 535 535 Proton acceptor (By similarity).
FT BINDING 94 94 ATP (By similarity).
FT BINDING 447 447 ATP (By similarity).
FT MOD_RES 54 54 Phosphoserine.
FT MOD_RES 221 221 Phosphoserine; by PDPK1 (Probable).
FT MOD_RES 307 307 Phosphoserine.
FT MOD_RES 348 348 Phosphothreonine.
FT MOD_RES 359 359 Phosphothreonine.
FT MOD_RES 363 363 Phosphoserine.
FT MOD_RES 369 369 Phosphoserine.
FT MOD_RES 380 380 Phosphoserine; by autocatalysis.
FT MOD_RES 573 573 Phosphothreonine.
FT MOD_RES 732 732 Phosphoserine.
FT VAR_SEQ 1 92 Missing (in isoform 3).
FT /FTId=VSP_041580.
FT VAR_SEQ 1 36 MPLAQLKEPWPLMELVPLDPENGQTSGEEAGLQPSK -> M
FT EQDPKPPRLRLWALIPWLPRKQRPRISQTSLPVPGPGSGPQ
FT RDS (in isoform 2).
FT /FTId=VSP_041380.
FT VARIANT 335 335 K -> T (in dbSNP:rs2229712).
FT /FTId=VAR_021864.
FT CONFLICT 609 609 A -> T (in Ref. 2; BAF85411).
FT CONFLICT 619 619 S -> G (in Ref. 2; BAF85411).
FT HELIX 59 61
FT STRAND 62 71
FT STRAND 74 81
FT STRAND 83 86
FT STRAND 90 96
FT STRAND 127 133
FT STRAND 136 141
FT HELIX 149 156
FT HELIX 161 180
FT HELIX 190 192
FT STRAND 193 195
FT STRAND 197 199
FT STRAND 201 203
FT HELIX 226 228
FT HELIX 231 234
FT HELIX 241 257
FT HELIX 267 276
FT HELIX 287 296
FT TURN 301 303
FT STRAND 307 310
FT HELIX 312 316
FT HELIX 319 321
FT HELIX 326 330
FT STRAND 418 427
FT STRAND 430 437
FT TURN 438 440
FT STRAND 443 450
FT HELIX 457 466
FT STRAND 475 480
FT STRAND 482 489
FT HELIX 497 502
FT STRAND 503 505
FT HELIX 509 528
FT HELIX 538 540
FT STRAND 541 545
FT HELIX 550 552
FT STRAND 553 555
FT TURN 574 576
FT HELIX 588 609
FT HELIX 622 631
FT HELIX 639 643
FT HELIX 646 655
FT HELIX 660 662
FT HELIX 666 670
FT HELIX 673 676
FT HELIX 678 680
FT HELIX 691 707
FT HELIX 717 719
FT HELIX 721 724
SQ SEQUENCE 735 AA; 82723 MW; 765731A4442A53DF CRC64;
MPLAQLKEPW PLMELVPLDP ENGQTSGEEA GLQPSKDEGV LKEISITHHV KAGSEKADPS
HFELLKVLGQ GSFGKVFLVR KVTRPDSGHL YAMKVLKKAT LKVRDRVRTK MERDILADVN
HPFVVKLHYA FQTEGKLYLI LDFLRGGDLF TRLSKEVMFT EEDVKFYLAE LALGLDHLHS
LGIIYRDLKP ENILLDEEGH IKLTDFGLSK EAIDHEKKAY SFCGTVEYMA PEVVNRQGHS
HSADWWSYGV LMFEMLTGSL PFQGKDRKET MTLILKAKLG MPQFLSTEAQ SLLRALFKRN
PANRLGSGPD GAEEIKRHVF YSTIDWNKLY RREIKPPFKP AVAQPDDTFY FDTEFTSRTP
KDSPGIPPSA GAHQLFRGFS FVATGLMEDD GKPRAPQAPL HSVVQQLHGK NLVFSDGYVV
KETIGVGSYS ECKRCVHKAT NMEYAVKVID KSKRDPSEEI EILLRYGQHP NIITLKDVYD
DGKHVYLVTE LMRGGELLDK ILRQKFFSER EASFVLHTIG KTVEYLHSQG VVHRDLKPSN
ILYVDESGNP ECLRICDFGF AKQLRAENGL LMTPCYTANF VAPEVLKRQG YDEGCDIWSL
GILLYTMLAG YTPFANGPSD TPEEILTRIG SGKFTLSGGN WNTVSETAKD LVSKMLHVDP
HQRLTAKQVL QHPWVTQKDK LPQSQLSHQD LQLVKGAMAA TYSALNSSKP TPQLKPIESS
ILAQRRVRKL PSTTL
//
MIM
601684
*RECORD*
*FIELD* NO
601684
*FIELD* TI
*601684 RIBOSOMAL PROTEIN S6 KINASE, 90-KD, 1; RPS6KA1
;;RIBOSOMAL S6 KINASE 1; RSK1;;
read moreMITOGEN-ACTIVATED PROTEIN KINASE-ACTIVATED PROTEIN KINASE 1A; MAPKAPK1A;;
MAPKAP KINASE 1A
*FIELD* TX
DESCRIPTION
The RSK (ribosomal S6 kinase) family comprises growth factor-regulated
serine/threonine kinases, known also as p90(rsk). Homologs of RSK exist
in several species. The highly conserved feature of all members of the
RSK family is the presence of 2 nonidentical kinase catalytic domains.
RSKs are implicated in the activation of the mitogen-activated kinase
(MAPK) cascade (see 176872) and the stimulation of cell proliferation
(at the transition between phases G0 and G1 of the cell cycle) and
differentiation.
CLONING
Moller et al. (1994) described the cloning and characterization of 3
genes encoding RSKs, which they called HU1 (RPS6KA1), HU2 (RPS6KA2;
601685), and HU3 (RPS6KA3; 300075). The HU1 cDNA (GenBank GENBANK
L07597) encodes a predicted 735-amino acid protein containing 2 distinct
consensus ATP-binding site sequences. Northern blot and RNase protection
analyses detected an approximately 3.5-kb HU1 transcript in lymphocytes,
skeletal muscle, liver, and adipose tissue.
Zeniou et al. (2002) determined the expression of the RSK1, RSK2
(300075), and RSK3 (601685) genes in various human tissues, during mouse
embryogenesis, and in mouse brain. The 3 RSK mRNAs were expressed in all
human tissues and brain regions tested, supporting functional
redundancy. However, tissue-specific variations in levels suggested that
the proteins may also serve specific roles. The mouse Rsk3 gene was
prominently expressed in the developing neural and sensory tissues,
whereas Rsk1 gene expression was the strongest in various other tissues
with high proliferative activity, suggesting distinct roles during
development. In adult mouse brain, the highest levels of Rsk2 expression
were observed in regions with high synaptic activity, including the
neocortex, the hippocampus, and Purkinje cells. The authors suggested
that in these areas, which are essential to cognitive function and
learning, the RSK1 and RSK3 genes may not be able to fully compensate
for a lack of RSK2 function.
GENE FUNCTION
Bonni et al. (1999) characterized the mechanism by which the RAS (see
190020)-MAPK signaling pathway (see 602448) mediates growth
factor-dependent cell survival. The MAP-activated kinases, the Rsks,
catalyzed the phosphorylation of the proapoptotic protein BAD (603167)
at ser112 both in vitro and in vivo. The Rsk-induced phosphorylation of
BAD at ser112 suppressed BAD-mediated apoptosis in neurons. The Rsks are
known to phosphorylate the transcription factor CREB (see 123810) at
ser133. Activated CREB promoted cell survival, and inhibition of CREB
phosphorylation at ser133 triggered apoptosis. Bonni et al. (1999)
suggested that the MAP kinase signaling pathway promotes cell survival
by a dual mechanism comprising the posttranslational modification and
inactivation of a component of the cell death machinery and the
increased transcription of prosurvival genes.
Bhatt and Ferrell (1999) demonstrated that Xenopus laevis egg extracts
immunodepleted of Rsk lost their capacity to undergo mitotic arrest in
response to activation of the Mos (190060)-MEK1 (176872)-p42 (603441)
MAPK cascade of protein kinases. Replenishing Rsk-depleted extracts with
catalytically competent Rsk protein restored the ability of the extracts
to undergo mitotic arrest. Bhatt and Ferrell (1999) concluded that Rsk
appears to be essential for cytostatic factor arrest.
Gross et al. (1999) investigated whether cytostatic factor arrest is
mediated by the protein kinase p90 Rsk, which is phosphorylated and
activated by MAPK, by expressing a constitutively activated form of Rsk
in Xenopus embryos. Expression of constitutively active Rsk resulted in
cleavage arrest, and cytologic analysis showed that arrested blastomeres
were in M phase with prominent spindles characteristic of meiotic
metaphase. Thus, Gross et al. (1999) concluded that Rsk appears to be
the mediator of MAPK-dependent cytostatic factor arrest in vertebrate
unfertilized eggs. Gross et al. (1999) found that because Rsk expression
did not activate the endogenous MAPK pathway, MAPK required no other
substrate for induction of cytostatic factor arrest. They also stated
that cytostatic factor arrest is not a consequence of direct regulation
of the spindle assembly checkpoint or the anaphase-promoting complex by
MAPK.
Cohen et al. (2005) used a structural bioinformatics approach to
identify 2 selectivity filters, a threonine and a cysteine, at defined
positions in the active site of p90 ribosomal protein S6 kinase (RSK). A
fluoromethylketone inhibitor, designed to exploit both selectivity
filters, potently and selectively inactivated RSK1 and RSK2 in mammalian
cells. Kinases with only one selectivity filter were resistant to the
inhibitor, yet they became sensitized after genetic introduction of the
second selectivity filter. Thus, Cohen et al. (2005) concluded that 2
amino acids that distinguish RSK from other protein kinases are
sufficient to confer inhibitor sensitivity.
Nishiyama et al. (2007) reported that in Xenopus eggs Erp1 (see 609110)
is a substrate of p90rsk, and that Mos (a mitogen-activated protein
kinase (MAPK) kinase kinase)-dependent phosphorylation of Erp1 by p90rsk
at thr336, ser342, and ser344 is crucial for both stabilizing Erp1 and
establishing cytostatic factor (CSF) arrest in meiosis II oocytes.
Semiquantitative analysis of CSF-arrested egg extracts revealed that the
Mos-dependent phosphorylation of Erp1 enhances, but does not generate,
the activity of Erp1 that maintains metaphase arrest. Nishiyama et al.
(2007) concluded that their results also suggested that Erp1 inhibits
cyclin B (see 123836) degradation by binding the anaphase-promoting
complex/cyclosome (APC/C) at its carboxy-terminal destruction box, and
this binding is also enhanced by the Mos-dependent phosphorylation.
Thus, Mos and Erp1 collaboratively establish and maintain metaphase II
arrest in Xenopus eggs.
Inoue et al. (2007) demonstrated that p90rsk, the kinase immediately
downstream from Mos-MAPK, directly targets Erp1 for CSF arrest in
Xenopus oocytes. Erp1 is synthesized immediately after meiosis I, and
the Mos-MAPK pathway or p90rsk is essential for CSF arrest by Erp1.
p90rsk can directly phosphorylate Erp1 on ser335/thr336 both in vivo and
in vitro, and upregulates both Erp1 stability and activity. Erp1 is also
present in early embryos, but has little CSF activity owing, at least in
part, to the absence of p90rsk activity. Inoue et al. (2007) concluded
that their results clarified the direct link of the classical Mos-MAPK
pathway to Erp1 in meiotic arrest of vertebrate oocytes.
MAPPING
By analysis of somatic cell hybrids, Moller et al. (1994) mapped the
RPS6KA1 gene to chromosome 3.
*FIELD* RF
1. Bhatt, R. R.; Ferrell, J. E., Jr.: The protein kinase p90 Rsk
as an essential mediator of cytostatic factor activity. Science 286:
1362-1365, 1999.
2. Bonni, A.; Brunet, A.; West, A. E.; Datta, S. R.; Takasu, M. A.;
Greenberg, M. E.: Cell survival promoted by the Ras-MAPK signaling
pathway by transcription-dependent and -independent mechanisms. Science 286:
1358-1362, 1999.
3. Cohen, M. S.; Zhang, C.; Shokat, K. M.; Taunton, J.: Structural
bioinformatics-based design of selective, irreversible kinase inhibitors. Science 308:
1318-1321, 2005.
4. Gross, S. D.; Schwab, M. S.; Lewellyn, A. L.; Maller, J. L.: Induction
of metaphase arrest in cleaving Xenopus embryos by the protein kinase
p90(Rsk). Science 286: 1365-1367, 1999.
5. Inoue, D.; Ohe, M.; Kanemori, Y.; Nobui, T.; Sagata, N.: A direct
link of the Mos-MAPK pathway to Erp1/Emi2 in meiotic arrest of Xenopus
laevis eggs. Nature 446: 1100-1104, 2007.
6. Moller, D. E.; Xia, C. H.; Tang, W.; Zhu, A. X.; Jakubowski, M.
: Human rsk isoforms: cloning and characterization of tissue-specific
expression. Am. J. Physiol. 266: C351-C359, 1994.
7. Nishiyama, T.; Ohsumi, K.; Kishimoto, T.: Phosphorylation of Erp1
by p90rsk is required for cytostatic factor arrest in Xenopus laevis
eggs. Nature 446: 1096-1099, 2007.
8. Zeniou, M.; Ding, T.; Trivier, E.; Hanauer, A.: Expression analysis
of RSK gene family members: the RSK2 gene, mutated in Coffin-Lowry
syndrome, is prominently expressed in brain structures essential for
cognitive function and learning. Hum. Molec. Genet. 11: 2929-2940,
2002.
*FIELD* CN
Ada Hamosh - updated: 5/30/2007
Ada Hamosh - updated: 6/15/2005
Ada Hamosh - updated: 12/21/2000
Ada Hamosh - updated: 11/12/1999
Patti M. Sherman - updated: 11/17/1998
*FIELD* CD
Victor A. McKusick: 2/14/1997
*FIELD* ED
alopez: 05/30/2007
terry: 5/30/2007
mgross: 3/13/2007
alopez: 6/15/2005
terry: 6/15/2005
mgross: 9/20/2004
tkritzer: 3/31/2004
terry: 3/21/2001
carol: 12/23/2000
terry: 12/21/2000
alopez: 11/12/1999
carol: 12/8/1998
psherman: 11/17/1998
terry: 7/30/1998
mark: 2/14/1997
*RECORD*
*FIELD* NO
601684
*FIELD* TI
*601684 RIBOSOMAL PROTEIN S6 KINASE, 90-KD, 1; RPS6KA1
;;RIBOSOMAL S6 KINASE 1; RSK1;;
read moreMITOGEN-ACTIVATED PROTEIN KINASE-ACTIVATED PROTEIN KINASE 1A; MAPKAPK1A;;
MAPKAP KINASE 1A
*FIELD* TX
DESCRIPTION
The RSK (ribosomal S6 kinase) family comprises growth factor-regulated
serine/threonine kinases, known also as p90(rsk). Homologs of RSK exist
in several species. The highly conserved feature of all members of the
RSK family is the presence of 2 nonidentical kinase catalytic domains.
RSKs are implicated in the activation of the mitogen-activated kinase
(MAPK) cascade (see 176872) and the stimulation of cell proliferation
(at the transition between phases G0 and G1 of the cell cycle) and
differentiation.
CLONING
Moller et al. (1994) described the cloning and characterization of 3
genes encoding RSKs, which they called HU1 (RPS6KA1), HU2 (RPS6KA2;
601685), and HU3 (RPS6KA3; 300075). The HU1 cDNA (GenBank GENBANK
L07597) encodes a predicted 735-amino acid protein containing 2 distinct
consensus ATP-binding site sequences. Northern blot and RNase protection
analyses detected an approximately 3.5-kb HU1 transcript in lymphocytes,
skeletal muscle, liver, and adipose tissue.
Zeniou et al. (2002) determined the expression of the RSK1, RSK2
(300075), and RSK3 (601685) genes in various human tissues, during mouse
embryogenesis, and in mouse brain. The 3 RSK mRNAs were expressed in all
human tissues and brain regions tested, supporting functional
redundancy. However, tissue-specific variations in levels suggested that
the proteins may also serve specific roles. The mouse Rsk3 gene was
prominently expressed in the developing neural and sensory tissues,
whereas Rsk1 gene expression was the strongest in various other tissues
with high proliferative activity, suggesting distinct roles during
development. In adult mouse brain, the highest levels of Rsk2 expression
were observed in regions with high synaptic activity, including the
neocortex, the hippocampus, and Purkinje cells. The authors suggested
that in these areas, which are essential to cognitive function and
learning, the RSK1 and RSK3 genes may not be able to fully compensate
for a lack of RSK2 function.
GENE FUNCTION
Bonni et al. (1999) characterized the mechanism by which the RAS (see
190020)-MAPK signaling pathway (see 602448) mediates growth
factor-dependent cell survival. The MAP-activated kinases, the Rsks,
catalyzed the phosphorylation of the proapoptotic protein BAD (603167)
at ser112 both in vitro and in vivo. The Rsk-induced phosphorylation of
BAD at ser112 suppressed BAD-mediated apoptosis in neurons. The Rsks are
known to phosphorylate the transcription factor CREB (see 123810) at
ser133. Activated CREB promoted cell survival, and inhibition of CREB
phosphorylation at ser133 triggered apoptosis. Bonni et al. (1999)
suggested that the MAP kinase signaling pathway promotes cell survival
by a dual mechanism comprising the posttranslational modification and
inactivation of a component of the cell death machinery and the
increased transcription of prosurvival genes.
Bhatt and Ferrell (1999) demonstrated that Xenopus laevis egg extracts
immunodepleted of Rsk lost their capacity to undergo mitotic arrest in
response to activation of the Mos (190060)-MEK1 (176872)-p42 (603441)
MAPK cascade of protein kinases. Replenishing Rsk-depleted extracts with
catalytically competent Rsk protein restored the ability of the extracts
to undergo mitotic arrest. Bhatt and Ferrell (1999) concluded that Rsk
appears to be essential for cytostatic factor arrest.
Gross et al. (1999) investigated whether cytostatic factor arrest is
mediated by the protein kinase p90 Rsk, which is phosphorylated and
activated by MAPK, by expressing a constitutively activated form of Rsk
in Xenopus embryos. Expression of constitutively active Rsk resulted in
cleavage arrest, and cytologic analysis showed that arrested blastomeres
were in M phase with prominent spindles characteristic of meiotic
metaphase. Thus, Gross et al. (1999) concluded that Rsk appears to be
the mediator of MAPK-dependent cytostatic factor arrest in vertebrate
unfertilized eggs. Gross et al. (1999) found that because Rsk expression
did not activate the endogenous MAPK pathway, MAPK required no other
substrate for induction of cytostatic factor arrest. They also stated
that cytostatic factor arrest is not a consequence of direct regulation
of the spindle assembly checkpoint or the anaphase-promoting complex by
MAPK.
Cohen et al. (2005) used a structural bioinformatics approach to
identify 2 selectivity filters, a threonine and a cysteine, at defined
positions in the active site of p90 ribosomal protein S6 kinase (RSK). A
fluoromethylketone inhibitor, designed to exploit both selectivity
filters, potently and selectively inactivated RSK1 and RSK2 in mammalian
cells. Kinases with only one selectivity filter were resistant to the
inhibitor, yet they became sensitized after genetic introduction of the
second selectivity filter. Thus, Cohen et al. (2005) concluded that 2
amino acids that distinguish RSK from other protein kinases are
sufficient to confer inhibitor sensitivity.
Nishiyama et al. (2007) reported that in Xenopus eggs Erp1 (see 609110)
is a substrate of p90rsk, and that Mos (a mitogen-activated protein
kinase (MAPK) kinase kinase)-dependent phosphorylation of Erp1 by p90rsk
at thr336, ser342, and ser344 is crucial for both stabilizing Erp1 and
establishing cytostatic factor (CSF) arrest in meiosis II oocytes.
Semiquantitative analysis of CSF-arrested egg extracts revealed that the
Mos-dependent phosphorylation of Erp1 enhances, but does not generate,
the activity of Erp1 that maintains metaphase arrest. Nishiyama et al.
(2007) concluded that their results also suggested that Erp1 inhibits
cyclin B (see 123836) degradation by binding the anaphase-promoting
complex/cyclosome (APC/C) at its carboxy-terminal destruction box, and
this binding is also enhanced by the Mos-dependent phosphorylation.
Thus, Mos and Erp1 collaboratively establish and maintain metaphase II
arrest in Xenopus eggs.
Inoue et al. (2007) demonstrated that p90rsk, the kinase immediately
downstream from Mos-MAPK, directly targets Erp1 for CSF arrest in
Xenopus oocytes. Erp1 is synthesized immediately after meiosis I, and
the Mos-MAPK pathway or p90rsk is essential for CSF arrest by Erp1.
p90rsk can directly phosphorylate Erp1 on ser335/thr336 both in vivo and
in vitro, and upregulates both Erp1 stability and activity. Erp1 is also
present in early embryos, but has little CSF activity owing, at least in
part, to the absence of p90rsk activity. Inoue et al. (2007) concluded
that their results clarified the direct link of the classical Mos-MAPK
pathway to Erp1 in meiotic arrest of vertebrate oocytes.
MAPPING
By analysis of somatic cell hybrids, Moller et al. (1994) mapped the
RPS6KA1 gene to chromosome 3.
*FIELD* RF
1. Bhatt, R. R.; Ferrell, J. E., Jr.: The protein kinase p90 Rsk
as an essential mediator of cytostatic factor activity. Science 286:
1362-1365, 1999.
2. Bonni, A.; Brunet, A.; West, A. E.; Datta, S. R.; Takasu, M. A.;
Greenberg, M. E.: Cell survival promoted by the Ras-MAPK signaling
pathway by transcription-dependent and -independent mechanisms. Science 286:
1358-1362, 1999.
3. Cohen, M. S.; Zhang, C.; Shokat, K. M.; Taunton, J.: Structural
bioinformatics-based design of selective, irreversible kinase inhibitors. Science 308:
1318-1321, 2005.
4. Gross, S. D.; Schwab, M. S.; Lewellyn, A. L.; Maller, J. L.: Induction
of metaphase arrest in cleaving Xenopus embryos by the protein kinase
p90(Rsk). Science 286: 1365-1367, 1999.
5. Inoue, D.; Ohe, M.; Kanemori, Y.; Nobui, T.; Sagata, N.: A direct
link of the Mos-MAPK pathway to Erp1/Emi2 in meiotic arrest of Xenopus
laevis eggs. Nature 446: 1100-1104, 2007.
6. Moller, D. E.; Xia, C. H.; Tang, W.; Zhu, A. X.; Jakubowski, M.
: Human rsk isoforms: cloning and characterization of tissue-specific
expression. Am. J. Physiol. 266: C351-C359, 1994.
7. Nishiyama, T.; Ohsumi, K.; Kishimoto, T.: Phosphorylation of Erp1
by p90rsk is required for cytostatic factor arrest in Xenopus laevis
eggs. Nature 446: 1096-1099, 2007.
8. Zeniou, M.; Ding, T.; Trivier, E.; Hanauer, A.: Expression analysis
of RSK gene family members: the RSK2 gene, mutated in Coffin-Lowry
syndrome, is prominently expressed in brain structures essential for
cognitive function and learning. Hum. Molec. Genet. 11: 2929-2940,
2002.
*FIELD* CN
Ada Hamosh - updated: 5/30/2007
Ada Hamosh - updated: 6/15/2005
Ada Hamosh - updated: 12/21/2000
Ada Hamosh - updated: 11/12/1999
Patti M. Sherman - updated: 11/17/1998
*FIELD* CD
Victor A. McKusick: 2/14/1997
*FIELD* ED
alopez: 05/30/2007
terry: 5/30/2007
mgross: 3/13/2007
alopez: 6/15/2005
terry: 6/15/2005
mgross: 9/20/2004
tkritzer: 3/31/2004
terry: 3/21/2001
carol: 12/23/2000
terry: 12/21/2000
alopez: 11/12/1999
carol: 12/8/1998
psherman: 11/17/1998
terry: 7/30/1998
mark: 2/14/1997