RBCC

Full text data of ARRB2

ARRB2 (ARB2, ARR2) [Confidence: low (only semi-automatic identification from reviews)]
Beta-arrestin-2 (Arrestin beta-2)

UniProt P32121
ID ARRB2_HUMAN Reviewed; 409 AA.
AC P32121; B4DLW0; B5B0C0; B7WPL3; D3DTK2; H0Y688; Q0Z8D3; Q2PP19;
read moreAC Q6ICT3; Q8N7Y2; Q9UEQ6;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 05-MAR-2002, sequence version 2.
DT 22-JAN-2014, entry version 138.
DE RecName: Full=Beta-arrestin-2;
DE AltName: Full=Arrestin beta-2;
GN Name=ARRB2; Synonyms=ARB2, ARR2;
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).
RC TISSUE=Thyroid;
RX PubMed=1587386; DOI=10.1016/0303-7207(92)90038-8;
RA Rapoport B., Kaufman K.D., Chamenbalk G.D.;
RT "Cloning of a member of the arrestin family from a human thyroid cDNA
RT library.";
RL Mol. Cell. Endocrinol. 84:R39-R43(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RA Yu Q.M., Zhou T.H., Wu Y.L., Cheng Z.J., Ma L., Pei G.;
RT "G-protein coupled receptor interaction with beta-arrestin 2 through
RT specific agonist stimulation.";
RL Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Sanchez-Laorden B.L., Jimenez-Cervantes C., Garcia-Borron J.C.;
RT "A new splice-variant of beta-arrestin 2 is involved in agonist-
RT induced MC1R endocytosis.";
RL Submitted (MAY-2006) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Lung;
RA Kaighin V.A., Martin A.L., Aronstam R.S.;
RT "Isolation of cDNA coding for human arrestin, beta 2 (ARRB2),
RT transcript variant 1.";
RL Submitted (JUL-2008) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4).
RC TISSUE=Brain, and Testis;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G;);
RL Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R.,
RA Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N.,
RA Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B.,
RA Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J.,
RA Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E.,
RA Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J.,
RA Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C.,
RA Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in
RT the human lineage.";
RL Nature 440:1045-1049(2006).
RN [9]
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 [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Muscle, and Pancreas;
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 [11]
RP SUBCELLULAR LOCATION, AND ASSOCIATION WITH GPCRS.
RX PubMed=9346876; DOI=10.1074/jbc.272.44.27497;
RA Barak L.S., Ferguson S.S.G., Zhang J., Caron M.G.;
RT "A beta-arrestin/green fluorescent protein biosensor for detecting G
RT protein-coupled receptor activation.";
RL J. Biol. Chem. 272:27497-27500(1997).
RN [12]
RP FUNCTION IN IN INTERNALIZATION OF CXCR4, INTERACTION WITH CXCR4, AND
RP MUTAGENESIS OF VAL-54.
RX PubMed=10644702; DOI=10.1074/jbc.275.4.2479;
RA Cheng Z.J., Zhao J., Sun Y., Hu W., Wu Y.L., Cen B., Wu G.-X., Pei G.;
RT "beta-arrestin differentially regulates the chemokine receptor CXCR4-
RT mediated signaling and receptor internalization, and this implicates
RT multiple interaction sites between beta-arrestin and CXCR4.";
RL J. Biol. Chem. 275:2479-2485(2000).
RN [13]
RP SUBCELLULAR LOCATION, AND ASSOCIATION WITH ANTAGONIST-STIMULATED
RP GPCRS.
RX PubMed=10748214; DOI=10.1074/jbc.M910348199;
RA Oakley R.H., Laporte S.A., Holt J.A., Caron M.G., Barak L.S.;
RT "Differential affinities of visual arrestin, beta arrestin1, and beta
RT arrestin2 for G protein-coupled receptors delineate two major classes
RT of receptors.";
RL J. Biol. Chem. 275:17201-17210(2000).
RN [14]
RP INTERACTION WITH HCK AND CXCR1.
RX PubMed=10973280; DOI=10.1038/79767;
RA Barlic J., Andrews J.D., Kelvin A.A., Bosinger S.E., DeVries M.E.,
RA Xu L., Dobransky T., Feldman R.D., Ferguson S.S., Kelvin D.J.;
RT "Regulation of tyrosine kinase activation and granule release through
RT beta-arrestin by CXCRI.";
RL Nat. Immunol. 1:227-233(2000).
RN [15]
RP SUBCELLULAR LOCATION, AND ASSOCIATION WITH ANTAGONIST-STIMULATED
RP GPCRS.
RX PubMed=11279203; DOI=10.1074/jbc.M101450200;
RA Oakley R.H., Laporte S.A., Holt J.A., Barak L.S., Caron M.G.;
RT "Molecular determinants underlying the formation of stable
RT intracellular G protein-coupled receptor-beta-arrestin complexes after
RT receptor endocytosis*.";
RL J. Biol. Chem. 276:19452-19460(2001).
RN [16]
RP FUNCTION IN INTERNALIZATION OF ADBR2, PHOSPHORYLATION AT THR-382,
RP INTERACTION WITH AP2B1; CLATHRIN AND SRC, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF THR-382.
RX PubMed=11877451; DOI=10.1074/jbc.M201379200;
RA Kim Y.-M., Barak L.S., Caron M.G., Benovic J.L.;
RT "Regulation of arrestin-3 phosphorylation by casein kinase II.";
RL J. Biol. Chem. 277:16837-16846(2002).
RN [17]
RP FUNCTION IN TP53-MEDIATED APOPTOSIS, AND INTERACTION WITH MDM2.
RX PubMed=12488444; DOI=10.1074/jbc.M210350200;
RA Wang P., Gao H., Ni Y., Wang B., Wu Y., Ji L., Qin L., Ma L., Pei G.;
RT "Beta-arrestin 2 functions as a G-protein-coupled receptor-activated
RT regulator of oncoprotein Mdm2.";
RL J. Biol. Chem. 278:6363-6370(2003).
RN [18]
RP FUNCTION IN DESENSITIZATION OF ADRB2, FUNCTION IN INTERNALIZATION OF
RP ADRB2, FUNCTION IN INTERNALIZATION OF AGTR1, AND FUNCTION IN
RP AGTR1-MEDIATED ERK SIGNALING.
RX PubMed=12582207; DOI=10.1073/pnas.262789099;
RA Ahn S., Nelson C.D., Garrison T.R., Miller W.E., Lefkowitz R.J.;
RT "Desensitization, internalization, and signaling functions of beta-
RT arrestins demonstrated by RNA interference.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:1740-1744(2003).
RN [19]
RP FUNCTION IN AGTR1-MEDIATED ERK SIGNALING.
RX PubMed=12949261; DOI=10.1073/pnas.1834556100;
RA Wei H., Ahn S., Shenoy S.K., Karnik S.S., Hunyady L., Luttrell L.M.,
RA Lefkowitz R.J.;
RT "Independent beta-arrestin 2 and G protein-mediated pathways for
RT angiotensin II activation of extracellular signal-regulated kinases 1
RT and 2.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:10782-10787(2003).
RN [20]
RP FUNCTION IN ENDOCYTOSIS OF TGFBR2 AND TGFBR3, FUNCTION IN TGF-BETA
RP SIGNALING, AND SUBCELLULAR LOCATION.
RX PubMed=12958365; DOI=10.1126/science.1083195;
RA Chen W., Kirkbride K.C., How T., Nelson C.D., Mo J., Frederick J.P.,
RA Wang X.-F., Lefkowitz R.J., Blobe G.C.;
RT "Beta-arrestin 2 mediates endocytosis of type III TGF-beta receptor
RT and down-regulation of its signaling.";
RL Science 301:1394-1397(2003).
RN [21]
RP FUNCTION IN AGTR1-MEDIATED ERK SIGNALING.
RX PubMed=14711824; DOI=10.1074/jbc.C300443200;
RA Ahn S., Wei H., Garrison T.R., Lefkowitz R.J.;
RT "Reciprocal regulation of angiotensin receptor-activated extracellular
RT signal-regulated kinases by beta-arrestins 1 and 2.";
RL J. Biol. Chem. 279:7807-7811(2004).
RN [22]
RP FUNCTION IN CCR7-MEDIATED ERK SIGNALING.
RX PubMed=15054093; DOI=10.1074/jbc.M402125200;
RA Kohout T.A., Nicholas S.L., Perry S.J., Reinhart G., Junger S.,
RA Struthers R.S.;
RT "Differential desensitization, receptor phosphorylation, beta-arrestin
RT recruitment, and ERK1/2 activation by the two endogenous ligands for
RT the CC chemokine receptor 7.";
RL J. Biol. Chem. 279:23214-23222(2004).
RN [23]
RP FUNCTION IN AGTR1-MEDIATED ERK SIGNALING.
RX PubMed=15205453; DOI=10.1074/jbc.M405878200;
RA Ahn S., Shenoy S.K., Wei H., Lefkowitz R.J.;
RT "Differential kinetic and spatial patterns of beta-arrestin and G
RT protein-mediated ERK activation by the angiotensin II receptor.";
RL J. Biol. Chem. 279:35518-35525(2004).
RN [24]
RP FUNCTION IN REGULATION OF NF-KAPPA-B, SUBCELLULAR LOCATION, AND
RP INTERACTION WITH CHUK AND RELA.
RX PubMed=15125834; DOI=10.1016/S1097-2765(04)00216-3;
RA Gao H., Sun Y., Wu Y., Luan B., Wang Y., Qu B., Pei G.;
RT "Identification of beta-arrestin2 as a G protein-coupled receptor-
RT stimulated regulator of NF-kappaB pathways.";
RL Mol. Cell 14:303-317(2004).
RN [25]
RP FUNCTION IN INTERNALIZATION OF SMO.
RX PubMed=15618519; DOI=10.1126/science.1104135;
RA Chen W., Ren X.R., Nelson C.D., Barak L.S., Chen J.K., Beachy P.A.,
RA de Sauvage F., Lefkowitz R.J.;
RT "Activity-dependent internalization of smoothened mediated by beta-
RT arrestin 2 and GRK2.";
RL Science 306:2257-2260(2004).
RN [26]
RP FUNCTION IN UBIQUITINATION OF IGF1R, AND INTERACTION WITH IGF1R AND
RP MDM2.
RX PubMed=15878855; DOI=10.1074/jbc.M501129200;
RA Girnita L., Shenoy S.K., Sehat B., Vasilcanu R., Girnita A.,
RA Lefkowitz R.J., Larsson O.;
RT "{beta}-Arrestin is crucial for ubiquitination and down-regulation of
RT the insulin-like growth factor-1 receptor by acting as adaptor for the
RT MDM2 E3 ligase.";
RL J. Biol. Chem. 280:24412-24419(2005).
RN [27]
RP INTERACTION WITH DUSP16, AND SUBCELLULAR LOCATION.
RX PubMed=15888437; DOI=10.1074/jbc.M501926200;
RA Willoughby E.A., Collins M.K.;
RT "Dynamic interaction between the dual specificity phosphatase MKP7 and
RT the JNK3 scaffold protein beta-arrestin 2.";
RL J. Biol. Chem. 280:25651-25658(2005).
RN [28]
RP FUNCTION IN IN INTERNALIZATION OF CCR5, AND INTERACTION WITH CCR5.
RX PubMed=16144840; DOI=10.1074/jbc.M500535200;
RA Huettenrauch F., Pollok-Kopp B., Oppermann M.;
RT "G protein-coupled receptor kinases promote phosphorylation and beta-
RT arrestin-mediated internalization of CCR5 homo- and hetero-
RT oligomers.";
RL J. Biol. Chem. 280:37503-37515(2005).
RN [29]
RP FUNCTION IN F2LR1-MEDIATED ERK SIGNALING.
RX PubMed=15475570; DOI=10.1124/mol.104.006072;
RA Stalheim L., Ding Y., Gullapalli A., Paing M.M., Wolfe B.L.,
RA Morris D.R., Trejo J.;
RT "Multiple independent functions of arrestins in the regulation of
RT protease-activated receptor-2 signaling and trafficking.";
RL Mol. Pharmacol. 67:78-87(2005).
RN [30]
RP FUNCTION IN AGTR1-MEDIATED CHEMOTAXIS.
RX PubMed=15635042; DOI=10.1124/mol.104.006270;
RA Hunton D.L., Barnes W.G., Kim J., Ren X.-R., Violin J.D., Reiter E.,
RA Milligan G., Patel D.D., Lefkowitz R.J.;
RT "Beta-arrestin 2-dependent angiotensin II type 1A receptor-mediated
RT pathway of chemotaxis.";
RL Mol. Pharmacol. 67:1229-1236(2005).
RN [31]
RP FUNCTION IN AVPR2-MEDIATED ERK SIGNALING.
RX PubMed=15671180; DOI=10.1073/pnas.0409534102;
RA Ren X.-R., Reiter E., Ahn S., Kim J., Chen W., Lefkowitz R.J.;
RT "Different G protein-coupled receptor kinases govern G protein and
RT beta-arrestin-mediated signaling of V2 vasopressin receptor.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:1448-1453(2005).
RN [32]
RP FUNCTION IN ENDOCYTOSIS OF SLC9A5, AND INTERACTION WITH SLC9A5.
RX PubMed=15699339; DOI=10.1073/pnas.0407444102;
RA Szabo E.Z., Numata M., Lukashova V., Iannuzzi P., Orlowski J.;
RT "beta-Arrestins bind and decrease cell-surface abundance of the Na+/H+
RT exchanger NHE5 isoform.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:2790-2795(2005).
RN [33]
RP INTERACTION WITH AP2B1.
RX PubMed=16516836; DOI=10.1016/j.devcel.2006.01.016;
RA Edeling M.A., Mishra S.K., Keyel P.A., Steinhauser A.L., Collins B.M.,
RA Roth R., Heuser J.E., Owen D.J., Traub L.M.;
RT "Molecular switches involving the AP-2 beta2 appendage regulate
RT endocytic cargo selection and clathrin coat assembly.";
RL Dev. Cell 10:329-342(2006).
RN [34]
RP FUNCTION IN ADRB2-MEDIATED ERK SIGNALING.
RX PubMed=16280323; DOI=10.1074/jbc.M506576200;
RA Shenoy S.K., Drake M.T., Nelson C.D., Houtz D.A., Xiao K.,
RA Madabushi S., Reiter E., Premont R.T., Lichtarge O., Lefkowitz R.J.;
RT "beta-arrestin-dependent, G protein-independent ERK1/2 activation by
RT the beta2 adrenergic receptor.";
RL J. Biol. Chem. 281:1261-1273(2006).
RN [35]
RP INTERACTION WITH HTR2C.
RX PubMed=16319069; DOI=10.1074/jbc.M508074200;
RA Marion S., Oakley R.H., Kim K.-M., Caron M.G., Barak L.S.;
RT "A beta-arrestin binding determinant common to the second
RT intracellular loops of rhodopsin family G protein-coupled receptors.";
RL J. Biol. Chem. 281:2932-2938(2006).
RN [36]
RP FUNCTION IN PTH1R-MEDIATED ERK SIGNALING.
RX PubMed=16492667; DOI=10.1074/jbc.M513380200;
RA Gesty-Palmer D., Chen M., Reiter E., Ahn S., Nelson C.D., Wang S.,
RA Eckhardt A.E., Cowan C.L., Spurney R.F., Luttrell L.M.,
RA Lefkowitz R.J.;
RT "Distinct beta-arrestin- and G protein-dependent pathways for
RT parathyroid hormone receptor-stimulated ERK1/2 activation.";
RL J. Biol. Chem. 281:10856-10864(2006).
RN [37]
RP FUNCTION IN THE NUCLEUS OF SPERMATOZOA, SUBCELLULAR LOCATION, AND
RP INTERACTION WITH DHX8; GAPDHS; H2AFX; KIF14 AND RCC1.
RX PubMed=16820410; DOI=10.1242/jcs.03046;
RA Neuhaus E.M., Mashukova A., Barbour J., Wolters D., Hatt H.;
RT "Novel function of beta-arrestin2 in the nucleus of mature
RT spermatozoa.";
RL J. Cell Sci. 119:3047-3056(2006).
RN [38]
RP FUNCTION IN TLR/IL-1 RECEPTOR SIGNALING, AND INTERACTION WITH TRAF6.
RX PubMed=16378096; DOI=10.1038/ni1294;
RA Wang Y., Tang Y., Teng L., Wu Y., Zhao X., Pei G.;
RT "Association of beta-arrestin and TRAF6 negatively regulates Toll-like
RT receptor-interleukin 1 receptor signaling.";
RL Nat. Immunol. 7:139-147(2006).
RN [39]
RP INTERACTION WITH GPR143.
RX PubMed=16524428; DOI=10.1111/j.1600-0749.2006.00292.x;
RA Innamorati G., Piccirillo R., Bagnato P., Palmisano I.,
RA Schiaffino M.V.;
RT "The melanosomal/lysosomal protein OA1 has properties of a G protein-
RT coupled receptor.";
RL Pigment Cell Res. 19:125-135(2006).
RN [40]
RP FUNCTION IN INTERNALIZATION OF ENG, FUNCTION IN TGF-BETA-MEDIATED ERK
RP SIGNALING, SUBCELLULAR LOCATION, AND INTERACTION WITH ENG.
RX PubMed=17540773; DOI=10.1074/jbc.M700176200;
RA Lee N.Y., Blobe G.C.;
RT "The interaction of endoglin with beta-arrestin2 regulates
RT transforming growth factor-beta-mediated ERK activation and migration
RT in endothelial cells.";
RL J. Biol. Chem. 282:21507-21517(2007).
RN [41]
RP FUNCTION IN INTERNALIZATION OF OPRD1, AND FUNCTION IN DEGRADATION OF
RP OPRD1.
RX PubMed=18419762; DOI=10.1111/j.1471-4159.2008.05431.x;
RA Zhang X., Wang F., Chen X., Chen Y., Ma L.;
RT "Post-endocytic fates of delta-opioid receptor are regulated by GRK2-
RT mediated receptor phosphorylation and distinct beta-arrestin
RT isoforms.";
RL J. Neurochem. 106:781-792(2008).
RN [42]
RP FUNCTION IN REGULATION OF INNATE IMMUNE RESPONSE, AND INTERACTION WITH
RP KIR2DL1; KIR2DL3 AND KIR2DL4.
RX PubMed=18604210; DOI=10.1038/ni.1635;
RA Yu M.-C., Su L.-L., Zou L., Liu Y., Wu N., Kong L., Zhuang Z.-H.,
RA Sun L., Liu H.P., Hu J.-H., Li D., Strominger J.L., Zang J.-W.,
RA Pei G., Ge B.-X.;
RT "An essential function for beta-arrestin 2 in the inhibitory signaling
RT of natural killer cells.";
RL Nat. Immunol. 9:898-907(2008).
RN [43]
RP FUNCTION IN TGFBR3-MEDIATED NF-KAPPA-B REGULATION.
RX PubMed=19325136; DOI=10.1093/carcin/bgp071;
RA You H.J., How T., Blobe G.C.;
RT "The type III transforming growth factor-beta receptor negatively
RT regulates nuclear factor kappa B signaling through its interaction
RT with beta-arrestin2.";
RL Carcinogenesis 30:1281-1287(2009).
RN [44]
RP FUNCTION IN INTERNALIZATION OF CCR2.
RX PubMed=19643177; DOI=10.1016/j.cellsig.2009.07.010;
RA Garcia Lopez M.A., Aguado Martinez A., Lamaze C., Martinez-Alonso C.,
RA Fischer T.;
RT "Inhibition of dynamin prevents CCL2-mediated endocytosis of CCR2 and
RT activation of ERK1/2.";
RL Cell. Signal. 21:1748-1757(2009).
RN [45]
RP INTERACTION WITH MAP2K4/MKK4.
RX PubMed=19782076; DOI=10.1016/j.febslet.2009.09.035;
RA Li X., MacLeod R., Dunlop A.J., Edwards H.V., Advant N., Gibson L.C.,
RA Devine N.M., Brown K.M., Adams D.R., Houslay M.D., Baillie G.S.;
RT "A scanning peptide array approach uncovers association sites within
RT the JNK/beta arrestin signalling complex.";
RL FEBS Lett. 583:3310-3316(2009).
RN [46]
RP FUNCTION IN MIP-1-BETA-STIMULATED CHEMOTAXIS.
RX PubMed=19620252; DOI=10.1189/jlb.0908551;
RA Cheung R., Malik M., Ravyn V., Tomkowicz B., Ptasznik A.,
RA Collman R.G.;
RT "An arrestin-dependent multi-kinase signaling complex mediates MIP-
RT 1beta/CCL4 signaling and chemotaxis of primary human macrophages.";
RL J. Leukoc. Biol. 86:833-845(2009).
RN [47]
RP UBIQUITINATION, DEUBIQUITINATION BY USP33, AND INTERACTION WITH USP33.
RX PubMed=19363159; DOI=10.1073/pnas.0901083106;
RA Shenoy S.K., Modi A.S., Shukla A.K., Xiao K., Berthouze M., Ahn S.,
RA Wilkinson K.D., Miller W.E., Lefkowitz R.J.;
RT "Beta-arrestin-dependent signaling and trafficking of 7-transmembrane
RT receptors is reciprocally regulated by the deubiquitinase USP33 and
RT the E3 ligase Mdm2.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:6650-6655(2009).
RN [48]
RP INTERACTION WITH CXCR4, AND FUNCTION.
RX PubMed=20048153; DOI=10.1074/jbc.M109.091173;
RA Busillo J.M., Armando S., Sengupta R., Meucci O., Bouvier M.,
RA Benovic J.L.;
RT "Site-specific phosphorylation of CXCR4 is dynamically regulated by
RT multiple kinases and results in differential modulation of CXCR4
RT signaling.";
RL J. Biol. Chem. 285:7805-7817(2010).
RN [49]
RP HYDROXYLATION AT PRO-176 AND PRO-181.
RX PubMed=21255264; DOI=10.1111/j.1582-4934.2011.01268.x;
RA Yan B., Huo Z., Liu Y., Lin X., Li J., Peng L., Zhao H., Zhou Z.N.,
RA Liang X., Liu Y., Zhu W., Liang D., Li L., Sun Y., Cui J., Chen Y.H.;
RT "Prolyl hydroxylase 2: a novel regulator of beta2 -adrenoceptor
RT internalization.";
RL J. Cell. Mol. Med. 15:2712-2722(2011).
RN [50]
RP INTERACTION WITH ACKR3.
RX PubMed=22300987; DOI=10.1016/j.biocel.2012.01.007;
RA Ray P., Mihalko L.A., Coggins N.L., Moudgil P., Ehrlich A.,
RA Luker K.E., Luker G.D.;
RT "Carboxy-terminus of CXCR7 regulates receptor localization and
RT function.";
RL Int. J. Biochem. Cell Biol. 44:669-678(2012).
RN [51]
RP FUNCTION, AND INTERACTION WITH ACKR3.
RX PubMed=22457824; DOI=10.1371/journal.pone.0034192;
RA Canals M., Scholten D.J., de Munnik S., Han M.K., Smit M.J., Leurs R.;
RT "Ubiquitination of CXCR7 controls receptor trafficking.";
RL PLoS ONE 7:E34192-E34192(2012).
RN [52]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH ACKR4.
RX PubMed=23341447; DOI=10.1074/jbc.M112.406108;
RA Watts A.O., Verkaar F., van der Lee M.M., Timmerman C.A., Kuijer M.,
RA van Offenbeek J., van Lith L.H., Smit M.J., Leurs R., Zaman G.J.,
RA Vischer H.F.;
RT "Beta-arrestin recruitment and G protein signaling by the atypical
RT human chemokine decoy receptor CCX-CKR.";
RL J. Biol. Chem. 288:7169-7181(2013).
CC -!- FUNCTION: Functions in regulating agonist-mediated G-protein
CC coupled receptor (GPCR) signaling by mediating both receptor
CC desensitization and resensitization processes. During homologous
CC desensitization, beta-arrestins bind to the GPRK-phosphorylated
CC receptor and sterically preclude its coupling to the cognate G-
CC protein; the binding appears to require additional receptor
CC determinants exposed only in the active receptor conformation. The
CC beta-arrestins target many receptors for internalization by acting
CC as endocytic adapters (CLASPs, clathrin-associated sorting
CC proteins) and recruiting the GPRCs to the adapter protein 2
CC complex 2 (AP-2) in clathrin-coated pits (CCPs). However, the
CC extent of beta-arrestin involvement appears to vary significantly
CC depending on the receptor, agonist and cell type. Internalized
CC arrestin-receptor complexes traffic to intracellular endosomes,
CC where they remain uncoupled from G-proteins. Two different modes
CC of arrestin-mediated internalization occur. Class A receptors,
CC like ADRB2, OPRM1, ENDRA, D1AR and ADRA1B dissociate from beta-
CC arrestin at or near the plasma membrane and undergo rapid
CC recycling. Class B receptors, like AVPR2, AGTR1, NTSR1, TRHR and
CC TACR1 internalize as a complex with arrestin and traffic with it
CC to endosomal vesicles, presumably as desensitized receptors, for
CC extended periods of time. Receptor resensitization then requires
CC that receptor-bound arrestin is removed so that the receptor can
CC be dephosphorylated and returned to the plasma membrane. Mediates
CC endocytosis of CCR7 following ligation of CCL19 but not CCL21.
CC Involved in internalization of P2RY1, P2RY4, P2RY6 and P2RY11 and
CC ATP-stimulated internalization of P2RY2. Involved in
CC phosphorylation-dependent internalization of OPRD1 and subsequent
CC recycling or degradation. Involved in ubiquitination of IGF1R.
CC Beta-arrestins function as multivalent adapter proteins that can
CC switch the GPCR from a G-protein signaling mode that transmits
CC short-lived signals from the plasma membrane via small molecule
CC second messengers and ion channels to a beta-arrestin signaling
CC mode that transmits a distinct set of signals that are initiated
CC as the receptor internalizes and transits the intracellular
CC compartment. Acts as signaling scaffold for MAPK pathways such as
CC MAPK1/3 (ERK1/2) and MAPK10 (JNK3). ERK1/2 and JNK3 activated by
CC the beta-arrestin scaffold are largely excluded from the nucleus
CC and confined to cytoplasmic locations such as endocytic vesicles,
CC also called beta-arrestin signalosomes. Acts as signaling scaffold
CC for the AKT1 pathway. GPCRs for which the beta-arrestin-mediated
CC signaling relies on both ARRB1 and ARRB2 (codependent regulation)
CC include ADRB2, F2RL1 and PTH1R. For some GPCRs the beta-arrestin-
CC mediated signaling relies on either ARRB1 or ARRB2 and is
CC inhibited by the other respective beta-arrestin form (reciprocal
CC regulation). Increases ERK1/2 signaling in AGTR1- and AVPR2-
CC mediated activation (reciprocal regulation). Involved in CCR7-
CC mediated ERK1/2 signaling involving ligand CCL19. Is involved in
CC type-1A angiotensin II receptor/AGTR1-mediated ERK activity. Is
CC involved in type-1A angiotensin II receptor/AGTR1-mediated MAPK10
CC activity. Is involved in dopamine-stimulated AKT1 activity in the
CC striatum by disrupting the association of AKT1 with its negative
CC regulator PP2A. Involved in AGTR1-mediated chemotaxis. Appears to
CC function as signaling scaffold involved in regulation of MIP-1-
CC beta-stimulated CCR5-dependent chemotaxis. Involved in attenuation
CC of NF-kappa-B-dependent transcription in response to GPCR or
CC cytokine stimulation by interacting with and stabilizing CHUK.
CC Suppresses UV-induced NF-kappa-B-dependent activation by
CC interacting with CHUK. The function is promoted by stimulation of
CC ADRB2 and dephosphorylation of ARRB2. Involved in p53/TP53-
CC mediated apoptosis by regulating MDM2 and reducing the MDM2-
CC mediated degradation of p53/TP53. May serve as nuclear messenger
CC for GPCRs. Upon stimulation of OR1D2, may be involved in
CC regulation of gene expression during the early processes of
CC fertilization. Also involved in regulation of receptors other than
CC GPCRs. Involved in endocytosis of TGFBR2 and TGFBR3 and down-
CC regulates TGF-beta signaling such as NF-kappa-B activation.
CC Involved in endocytosis of low-density lipoprotein receptor/LDLR.
CC Involved in endocytosis of smoothened homolog/Smo, which also
CC requires ADRBK1. Involved in endocytosis of SLC9A5. Involved in
CC endocytosis of ENG and subsequent TGF-beta-mediated ERK activation
CC and migration of epithelial cells. Involved in Toll-like receptor
CC and IL-1 receptor signaling through the interaction with TRAF6
CC which prevents TRAF6 autoubiquitination and oligomerization
CC required for activation of NF-kappa-B and JUN. Involved in insulin
CC resistance by acting as insulin-induced signaling scaffold for
CC SRC, AKT1 and INSR. Involved in regulation of inhibitory signaling
CC of natural killer cells by recruiting PTPN6 and PTPN11 to KIR2DL1.
CC Involved in IL8-mediated granule release in neutrophils. Involved
CC in the internalization of the atypical chemokine receptor ACKR3.
CC -!- SUBUNIT: Homooligomer; the self-association is mediated by InsP6-
CC binding (Probable). Heterooligomer with ARRB1; the association is
CC mediated by InsP6-binding. Interacts with ADRB2 AND CHRM2.
CC Interacts with PDE4A. Interacts with PDE4D. Interacts with MAPK10,
CC MAPK1 and MAPK3. Interacts with DRD2. Interacts with FSHR.
CC Interacts with CLTC. Interacts with HTR2C. Interacts with CCR5.
CC Interacts with CXCR4. Interacts with SRC. Interacts with DUSP16;
CC the interaction is interrupted by stimulation of AGTR1 and
CC activation of MAPK10. Interacts with CHUK; the interaction is
CC enhanced stimulation of ADRB2. Interacts with RELA. Interacts with
CC MDM2; the interaction is enhanced by activation of GPCRs.
CC Interacts with SLC9A5. Interacts with TRAF6. Interacts with IGF1R.
CC Interacts with ENG. Interacts with KIR2DL1, KIR2DL3 and KIR2DL4.
CC Interacts with LDLR. Interacts with AP2B1. Interacts with C5AR1.
CC Interacts with RAF1. Interacts with MAP2K1. Interacts with MAPK1.
CC Interacts with MAPK10; the interaction enhances MAPK10 activation
CC by MAP3K5. Interacts with MAP2K4; the interaction is enhanced by
CC presence of MAP3K5 and MAPK10. Interacts with MAP3K5. Interacts
CC with AKT1. Interacts with IKBKB and MAP3K14. Interacts with SMO
CC (activated). Interacts with GSK3A and GSK3B. Associates with
CC protein phosphatase 2A (PP2A) (By similarity). Interacts with
CC DHX8; the interaction is detected in the nucleus upon OR1D2
CC stimulation. Interacts with GAPDHS; the interaction is detected in
CC the nucleus upon OR1D2 stimulation. Interacts with H2AFX; the
CC interaction is detected in the nucleus upon OR1D2 stimulation.
CC Interacts with KIF14; the interaction is detected in the nucleus
CC upon OR1D2 stimulation. Interacts with RCC1; the interaction is
CC detected in the nucleus upon OR1D2 stimulation. Interacts with
CC CXCR4; the interaction is dependent on C-terminal phosphorylation
CC of CXCR4 and allows activation of MAPK1 and MAPK3. Interacts with
CC GPR143. Interacts with HCK and CXCR1 (phosphorylated). Interacts
CC with ACKR3 and ACKR4.
CC -!- INTERACTION:
CC P31750:Akt1 (xeno); NbExp=3; IntAct=EBI-714559, EBI-298707;
CC P62158:CALM3; NbExp=3; IntAct=EBI-714559, EBI-397435;
CC P06396:GSN; NbExp=3; IntAct=EBI-714559, EBI-351506;
CC P11142:HSPA8; NbExp=4; IntAct=EBI-714559, EBI-351896;
CC Q99683:MAP3K5; NbExp=2; IntAct=EBI-714559, EBI-476263;
CC P19338:NCL; NbExp=3; IntAct=EBI-714559, EBI-346967;
CC Q14978:NOLC1; NbExp=3; IntAct=EBI-714559, EBI-396155;
CC Q9Q2G4:ORF (xeno); NbExp=3; IntAct=EBI-714559, EBI-6248094;
CC P14618:PKM; NbExp=4; IntAct=EBI-714559, EBI-353408;
CC P35813:PPM1A; NbExp=3; IntAct=EBI-714559, EBI-989143;
CC O75688:PPM1B; NbExp=3; IntAct=EBI-714559, EBI-1047039;
CC Q13523:PRPF4B; NbExp=3; IntAct=EBI-714559, EBI-395940;
CC P40417:rl (xeno); NbExp=4; IntAct=EBI-714559, EBI-867790;
CC P06702:S100A9; NbExp=2; IntAct=EBI-714559, EBI-1055001;
CC Q15208:STK38; NbExp=3; IntAct=EBI-714559, EBI-458376;
CC Q13428:TCOF1; NbExp=3; IntAct=EBI-714559, EBI-396105;
CC P27348:YWHAQ; NbExp=3; IntAct=EBI-714559, EBI-359854;
CC O95218:ZRANB2; NbExp=4; IntAct=EBI-714559, EBI-1051583;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Cell membrane. Membrane,
CC clathrin-coated pit (By similarity). Cytoplasmic vesicle.
CC Note=Translocates to the plasma membrane and colocalizes with
CC antagonist-stimulated GPCRs.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=P32121-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P32121-3; Sequence=VSP_008195;
CC Name=3;
CC IsoId=P32121-2; Sequence=VSP_008194, VSP_008195;
CC Note=No experimental confirmation available;
CC Name=4;
CC IsoId=P32121-4; Sequence=VSP_044697;
CC Note=No experimental confirmation available;
CC Name=5;
CC IsoId=P32121-5; Sequence=VSP_008194;
CC -!- DOMAIN: The [DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif mediates
CC interaction the AP-2 complex subunit AP2B1 (By similarity).
CC -!- PTM: Phosphorylated at Thr-382 in the cytoplasm; probably
CC dephosphorylated at the plasma membrane. The phosphorylation does
CC not regulate internalization and recycling of ADRB2, interaction
CC with clathrin or AP2B1.
CC -!- PTM: The ubiquitination status appears to regulate the formation
CC and trafficking of beta-arrestin-GPCR complexes and signaling.
CC Ubiquitination appears to occurr GPCR-specifc. Ubiquitinated by
CC MDM2; the ubiquitination is required for rapid internalization of
CC ADRB2. Deubiquitinated by USP33; the deubiquitination leads to a
CC dissociation of the beta-arrestin-GPCR complex. Stimulation of a
CC class A GPCR, such as ADRB2, induces transient ubiquitination and
CC subsequently promotes association with USP33. Stimulation of a
CC class B GPCR promotes a sustained ubiquitination.
CC -!- PTM: Hydroxylation by PHD2 modulates the rate of internalization
CC by slowing down recruitment to the plasma membrane and inhibiting
CC subsequent co-internalization with class A receptors.
CC -!- SIMILARITY: Belongs to the arrestin family.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Arrestin entry;
CC URL="http://en.wikipedia.org/wiki/Arrestin";
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DR EMBL; Z11501; CAA77577.1; -; mRNA.
DR EMBL; AF106941; AAC99468.1; -; mRNA.
DR EMBL; DQ664180; ABG47460.1; -; mRNA.
DR EMBL; EU883572; ACG60646.1; -; mRNA.
DR EMBL; AK097542; BAC05094.1; -; mRNA.
DR EMBL; AK297181; BAG59672.1; -; mRNA.
DR EMBL; CR450310; CAG29306.1; -; mRNA.
DR EMBL; DQ314866; ABC40725.1; -; Genomic_DNA.
DR EMBL; AC091153; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471108; EAW90421.1; -; Genomic_DNA.
DR EMBL; CH471108; EAW90422.1; -; Genomic_DNA.
DR EMBL; BC007427; AAH07427.1; -; mRNA.
DR EMBL; BC067368; AAH67368.1; -; mRNA.
DR PIR; S18984; S18984.
DR RefSeq; NP_001244257.1; NM_001257328.1.
DR RefSeq; NP_001244258.1; NM_001257329.1.
DR RefSeq; NP_001244259.1; NM_001257330.1.
DR RefSeq; NP_001244260.1; NM_001257331.1.
DR RefSeq; NP_004304.1; NM_004313.3.
DR RefSeq; NP_945355.1; NM_199004.1.
DR UniGene; Hs.435811; -.
DR ProteinModelPortal; P32121; -.
DR SMR; P32121; 6-393.
DR DIP; DIP-40089N; -.
DR IntAct; P32121; 280.
DR MINT; MINT-216692; -.
DR STRING; 9606.ENSP00000269260; -.
DR PhosphoSite; P32121; -.
DR DMDM; 20141230; -.
DR PaxDb; P32121; -.
DR PRIDE; P32121; -.
DR DNASU; 409; -.
DR Ensembl; ENST00000269260; ENSP00000269260; ENSG00000141480.
DR Ensembl; ENST00000346341; ENSP00000341895; ENSG00000141480.
DR Ensembl; ENST00000381488; ENSP00000370898; ENSG00000141480.
DR Ensembl; ENST00000412477; ENSP00000403701; ENSG00000141480.
DR GeneID; 409; -.
DR KEGG; hsa:409; -.
DR UCSC; uc002fyj.3; human.
DR CTD; 409; -.
DR GeneCards; GC17P004613; -.
DR HGNC; HGNC:712; ARRB2.
DR MIM; 107941; gene.
DR neXtProt; NX_P32121; -.
DR PharmGKB; PA60; -.
DR eggNOG; NOG302111; -.
DR HOVERGEN; HBG002399; -.
DR KO; K04439; -.
DR OMA; KPHDHIT; -.
DR OrthoDB; EOG79W954; -.
DR PhylomeDB; P32121; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_604; Hemostasis.
DR SignaLink; P32121; -.
DR ChiTaRS; ARRB2; human.
DR GeneWiki; Arrestin_beta_2; -.
DR GenomeRNAi; 409; -.
DR NextBio; 1719; -.
DR PRO; PR:P32121; -.
DR ArrayExpress; P32121; -.
DR Bgee; P32121; -.
DR CleanEx; HS_ARRB2; -.
DR Genevestigator; P32121; -.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:Ensembl.
DR GO; GO:0005905; C:coated pit; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0043197; C:dendritic spine; IEA:Ensembl.
DR GO; GO:0030139; C:endocytic vesicle; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0014069; C:postsynaptic density; IEA:Ensembl.
DR GO; GO:0045211; C:postsynaptic membrane; IEA:Ensembl.
DR GO; GO:0032947; F:protein complex scaffold; IDA:BHF-UCL.
DR GO; GO:0007628; P:adult walking behavior; IEA:Ensembl.
DR GO; GO:0007420; P:brain development; IEA:Ensembl.
DR GO; GO:0060326; P:cell chemotaxis; IMP:UniProtKB.
DR GO; GO:0002032; P:desensitization of G-protein coupled receptor protein signaling pathway by arrestin; IMP:UniProtKB.
DR GO; GO:0050965; P:detection of temperature stimulus involved in sensory perception of pain; IEA:Ensembl.
DR GO; GO:0042699; P:follicle-stimulating hormone signaling pathway; IEA:Ensembl.
DR GO; GO:0002031; P:G-protein coupled receptor internalization; IDA:UniProtKB.
DR GO; GO:0034260; P:negative regulation of GTPase activity; IEA:Ensembl.
DR GO; GO:0032691; P:negative regulation of interleukin-1 beta production; IEA:Ensembl.
DR GO; GO:0032695; P:negative regulation of interleukin-12 production; IEA:Ensembl.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; IEA:Ensembl.
DR GO; GO:0045953; P:negative regulation of natural killer cell mediated cytotoxicity; IMP:UniProtKB.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0034392; P:negative regulation of smooth muscle cell apoptotic process; IEA:Ensembl.
DR GO; GO:0034122; P:negative regulation of toll-like receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IEA:Ensembl.
DR GO; GO:0007219; P:Notch signaling pathway; TAS:Reactome.
DR GO; GO:0030168; P:platelet activation; TAS:Reactome.
DR GO; GO:0051928; P:positive regulation of calcium ion transport; IEA:Ensembl.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:UniProtKB.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IEA:Ensembl.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling cascade; IEA:Ensembl.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IGI:BHF-UCL.
DR GO; GO:0002092; P:positive regulation of receptor internalization; IMP:UniProtKB.
DR GO; GO:0032226; P:positive regulation of synaptic transmission, dopaminergic; IEA:Ensembl.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0016567; P:protein ubiquitination; IMP:UniProtKB.
DR GO; GO:0060765; P:regulation of androgen receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0006366; P:transcription from RNA polymerase II promoter; IDA:UniProtKB.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IDA:BHF-UCL.
DR Gene3D; 2.60.40.640; -; 1.
DR Gene3D; 2.60.40.840; -; 1.
DR InterPro; IPR000698; Arrestin.
DR InterPro; IPR011021; Arrestin-like_N.
DR InterPro; IPR014752; Arrestin_C.
DR InterPro; IPR011022; Arrestin_C-like.
DR InterPro; IPR017864; Arrestin_CS.
DR InterPro; IPR014753; Arrestin_N.
DR InterPro; IPR014756; Ig_E-set.
DR PANTHER; PTHR11792; PTHR11792; 1.
DR Pfam; PF02752; Arrestin_C; 1.
DR Pfam; PF00339; Arrestin_N; 1.
DR PRINTS; PR00309; ARRESTIN.
DR SMART; SM01017; Arrestin_C; 1.
DR SUPFAM; SSF81296; SSF81296; 2.
DR PROSITE; PS00295; ARRESTINS; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Coated pit; Complete proteome;
KW Cytoplasm; Cytoplasmic vesicle; Hydroxylation; Membrane; Nucleus;
KW Phosphoprotein; Protein transport; Reference proteome;
KW Signal transduction inhibitor; Transport; Ubl conjugation.
FT CHAIN 1 409 Beta-arrestin-2.
FT /FTId=PRO_0000205199.
FT REGION 240 409 Interaction with TRAF6.
FT REGION 363 409 Interaction with AP2B1.
FT MOTIF 385 395 [DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif.
FT MOD_RES 48 48 Phosphotyrosine (By similarity).
FT MOD_RES 176 176 Hydroxyproline; by PHD2.
FT MOD_RES 181 181 Hydroxyproline; by PHD2.
FT MOD_RES 360 360 Phosphoserine (By similarity).
FT MOD_RES 382 382 Phosphothreonine.
FT VAR_SEQ 39 53 Missing (in isoform 3 and isoform 5).
FT /FTId=VSP_008194.
FT VAR_SEQ 119 119 T -> TVRMPLPSEGQGAGAGTVSGVG (in isoform
FT 4).
FT /FTId=VSP_044697.
FT VAR_SEQ 360 360 S -> SAPTPTPPLPVPP (in isoform 2 and
FT isoform 3).
FT /FTId=VSP_008195.
FT MUTAGEN 11 11 K->A: Abolishes interaction with CHUK;
FT when associated with A-12; A-230 and A-
FT 231.
FT MUTAGEN 12 12 K->A: Abolishes interaction with CHUK;
FT when associated with A-11; A-230 and A-
FT 231.
FT MUTAGEN 54 54 V->A: Inhibits internalization of CXCR4;
FT no effect on interaction with CXCR4.
FT MUTAGEN 230 230 K->A: Abolishes interaction with CHUK;
FT when associated with A-11; A-12 and A-
FT 231.
FT MUTAGEN 231 231 K->A: Abolishes interaction with CHUK;
FT when associated with A-11; A-12 and A-
FT 230.
FT MUTAGEN 360 360 S->A,D: Reduces interaction with CHUK;
FT when associated with A-382.
FT MUTAGEN 382 382 T->A,D: Reduces interaction with CHUK;
FT when associated with A-360.
FT MUTAGEN 382 382 T->A: Loss of phosphorylation.
FT CONFLICT 13 13 S -> P (in Ref. 5; BAG59672).
FT CONFLICT 189 189 R -> P (in Ref. 1; CAA77577).
FT CONFLICT 190 190 H -> R (in Ref. 3; ABG47460).
FT CONFLICT 192 192 L -> P (in Ref. 6; CAG29306).
FT CONFLICT 366 366 D -> G (in Ref. 5; BAG59672).
SQ SEQUENCE 409 AA; 46106 MW; DEEC507D4A7B84FF CRC64;
MGEKPGTRVF KKSSPNCKLT VYLGKRDFVD HLDKVDPVDG VVLVDPDYLK DRKVFVTLTC
AFRYGREDLD VLGLSFRKDL FIATYQAFPP VPNPPRPPTR LQDRLLRKLG QHAHPFFFTI
PQNLPCSVTL QPGPEDTGKA CGVDFEIRAF CAKSLEEKSH KRNSVRLVIR KVQFAPEKPG
PQPSAETTRH FLMSDRSLHL EASLDKELYY HGEPLNVNVH VTNNSTKTVK KIKVSVRQYA
DICLFSTAQY KCPVAQLEQD DQVSPSSTFC KVYTITPLLS DNREKRGLAL DGKLKHEDTN
LASSTIVKEG ANKEVLGILV SYRVKVKLVV SRGGDVSVEL PFVLMHPKPH DHIPLPRPQS
AAPETDVPVD TNLIEFDTNY ATDDDIVFED FARLRLKGMK DDDYDDQLC
//

MIM 107941
*RECORD*
*FIELD* NO
107941
*FIELD* TI
*107941 ARRESTIN, BETA, 2; ARRB2
;;BETA-ARRESTIN 2; ARB2;;
BARR2
*FIELD* TX

CLONING
read more
Using a low stringency hybridization technique to screen a rat brain
cDNA library, Attramadal et al. (1992) isolated cDNA clones representing
2 distinct beta-arrestin-like genes. One of the cDNAs is the rat homolog
of bovine beta-arrestin (beta-arrestin-1; ARB1; 107940). In addition,
Attramadal et al. (1992) isolated a cDNA clone encoding a novel
beta-arrestin-related protein, which they termed beta-arrestin-2. ARB2
exhibited 78% amino acid identity with ARB1. The primary structure of
these proteins delineated a family of proteins that regulate receptor
coupling to G proteins. ARB1 and ARB2 are predominantly localized in
neuronal tissues and in the spleen.

GENE FUNCTION

Beta-arrestins were originally discovered in the context of
heterotrimeric G protein-coupled receptor desensitization, but they also
function in internalization and signaling of these receptors. Using a
yeast 2-hybrid screen, McDonald et al. (2000) identified JNK3 (602897)
as a binding partner of ARBB2. These results were confirmed by
coimmunoprecipitation from mouse brain extracts and cotransfection in
COS-7 cells. The upstream JNK activators apoptosis signal-regulating
kinase-1 (ASK1; 602448) and MAP2K4 (601335) were also found in complex
with ARBB2. Cellular transfection of ARBB2 caused cytosolic retention of
JNK3 and enhanced JNK3 phosphorylation stimulated by ASK1. Moreover,
stimulation of the angiotensin II type 1A receptor (AGTR1; 106165)
activated JNK3 and triggered the colocalization of ARBB2 and active JNK3
to intracellular vesicles. Thus, McDonald et al. (2000) concluded that
ARBB2 acts as a scaffold protein, which brings the spatial distribution
and activity of this MAPK module under the control of a G
protein-coupled receptor.

Alloway et al. (2000) demonstrated the existence of stable, persistent
complexes between rhodopsin (180380) and its regulatory protein arrestin
in several different retinal degeneration mutants in Drosophila.
Elimination of these rhodopsin-arrestin complexes by removing either
rhodopsin or arrestin rescues the degeneration phenotype. Furthermore,
Alloway et al. (2000) showed that the accumulation of these complexes
triggers apoptotic cell death and that the observed retinal degeneration
requires the endocytic machinery. Thus, the endocytosis of
rhodopsin-arrestin complexes may be a molecular mechanism for the
initiation of retinal degeneration. Alloway et al. (2000) proposed that
an identical mechanism may be responsible for the pathology found in a
subset of human retinal degenerative disorders.

Kiselev et al. (2000) uncovered the pathway by which activation of
rhodopsin in Drosophila mediates apoptosis through a G
protein-independent mechanism. They found that the process involves the
formation of membrane complexes of phosphorylated, activated rhodopsin
and its inhibitory protein arrestin, and subsequent clathrin-dependent
endocytosis of these complexes into a cytoplasmic compartment.

Although trafficking and degradation of several membrane proteins are
regulated by ubiquitination catalyzed by E3 ubiquitin ligases, the
connection of ubiquitination with regulation of mammalian G
protein-coupled receptor function was unclear. Shenoy et al. (2001)
demonstrated that agonist stimulation of endogenous or transfected
beta-2 adrenergic receptors (ADRB2; 109690) led to rapid ubiquitination
of both the receptors and the receptor regulatory protein,
beta-arrestin. Moreover, proteasome inhibitors reduced receptor
internalization and degradation, thus implicating a role for the
ubiquitination machinery in the trafficking of the beta-2 adrenergic
receptor. Receptor ubiquitination required beta-arrestin, which bound
the E3 ubiquitin ligase MDM2 (164785). Abrogation of beta-arrestin
ubiquitination, either by expression in MDM2-null cells or by
dominant-negative forms of MDM2 lacking E3 ligase activity, inhibited
receptor internalization with marginal effects on receptor degradation.
However, a beta-2 adrenergic receptor mutant lacking lysine residues,
which was not ubiquitinated, was internalized normally but was degraded
ineffectively. Shenoy et al. (2001) concluded that their results
delineated an adaptor role of beta-arrestin in mediating the
ubiquitination of the beta-2 adrenergic receptor and indicated that
ubiquitination of the receptor and of beta-arrestin have distinct and
obligatory roles in the trafficking and degradation of this prototypic G
protein-coupled receptor.

Chen et al. (2003) found that beta-arrestin-2 binds to the single
transmembrane-spanning type III transforming growth factor-beta receptor
(TGFBR3; 600742), also known as beta-glycan. Binding of beta-arrestin-2
to TGFBR3 was also triggered by phosphorylation of the receptor on its
cytoplasmic domain, likely at threonine-841. Chen et al. (2003) found
that phosphorylation was mediated by the type II TGF-beta receptor
(TGFBR2; 190182), which is itself a kinase, rather than by a G
protein-coupled receptor kinase. Association with beta-arrestin-2 led to
internalization of both receptors and downregulation of TGF-beta
signaling. Chen et al. (2003) concluded that the regulatory actions of
beta-arrestins are broader than previously appreciated, extending to the
TGF-beta receptor family as well.

Chen et al. (2003) found that endocytosis of frizzled-4 (FZD4; 604579)
in human embryonic kidney cells was dependent on added WNT5A (164975)
protein and was accomplished by the multifunctional adaptor protein
beta-arrestin-2, which was recruited to FZD4 by binding to
phosphorylated dishevelled-2 (DVL2; 602151). The authors concluded that
their findings provided a previously unrecognized mechanism for receptor
recruitment of beta-arrestin and demonstrated that dishevelled plays an
important role in the endocytosis of frizzled, as well as in promoting
signaling.

Chen et al. (2004) found that 2 molecules interact with mammalian
Smoothened (SMO; 601500) in an activation-dependent manner: G
protein-coupled receptor kinase-2 (GRK2; 109635) leads to
phosphorylation of Smo, and beta-arrestin-2 fused to green fluorescent
protein interacts with Smo. These 2 processes promote endocytosis of Smo
in clathrin-coated pits. Ptc (601309) inhibits association of
beta-arrestin-2 with Smo, and this inhibition is relieved in cells
treated with Shh (600725). A Smo agonist stimulated and a Smo antagonist
(cyclopamine) inhibited both phosphorylation of Smo by Grk2 and
interaction of beta-arrestin-2 with Smo. Chen et al. (2004) suggested
that beta-arrestin-2 and Grk2 are thus potential mediators of signaling
by activated Smo.

Kovacs et al. (2008) demonstrated that beta-arrestins mediate the
activity-dependent interaction of SMO and the kinesin motor protein
KIF3A (604683). This multimeric complex localized to primary cilia and
was disrupted in cells transfected with beta-arrestin small interfering
RNA. Beta-arrestin-1 (ARRB1; 107940) or beta-arrestin-2 depletion
prevented the localization of SMO to primary cilia and the SMO-dependent
activation of GLI (165220). Kovacs et al. (2008) concluded that their
results suggested roles for beta-arrestin in mediating the intracellular
transport of a 7-transmembrane receptor to its obligate subcellular
location for signaling.

Luan et al. (2009) demonstrated that in diabetic mouse models, including
the db/db mouse (601007), beta-arrestin-2 is severely downregulated.
Knockdown of beta-arrestin-2 exacerbated insulin resistance, whereas
administration of beta-arrestin-2 restored insulin sensitivity in mice.
Further investigation revealed that insulin stimulates the formation of
a beta-arrestin-2 signal complex in which beta-arrestin-2 scaffolds Akt
(164730) and Src (190090) to insulin receptor (147670). Loss or
dysfunction of beta-arrestin-2 resulted in deficiency of this signal
complex and disturbance of insulin signaling in vivo, thereby
contributing to the development of insulin resistance and progression of
type 2 diabetes.

Using immunofluorescence microscopy, Coureuil et al. (2010) demonstrated
that Neisseria meningitidis (Nm) colonies at the cell surface of human
brain endothelial cells promoted translocation of ARRB1 and ARRB2 to the
inner surface of the plasma membrane, facing the bacteria. ARRBs
translocated under the colonies served as a scaffolding platform for
signaling events elicited by Nm. ADRB2 was the only G protein-coupled
receptor expressed in the cell line that played a permissive role in the
formation of cortical plaques under colonies and in bacterial crossing
of cell monolayers. Coureuil et al. (2010) concluded that the ADRB2/ARRB
signaling pathway is required for Nm to promote stable adhesion to brain
endothelial cells and subsequent crossing of the blood-brain barrier.

MAPPING

By fluorescence in situ hybridization, Calabrese et al. (1994) mapped
the ARRB2 gene to 17p13.

ANIMAL MODEL

Bohn et al. (1999) generated beta-arrestin-2 knockout mice by
inactivation of the gene by homologous recombination. Homozygous mutant
mice were viable and had no gross phenotypic abnormalities. However,
after administration of morphine, obvious differences became apparent
between the genotypes. Beta-arrestin-2 knockout mice had remarkable
potentiation and prolongation of the analgesic effect of morphine,
suggesting that mu-opioid receptor (600018) desensitization was
impaired. Even at doses of morphine that were subanalgesic in wildtype
mice, homozygous mutant animals displayed a significant increase in
their nociceptive thresholds. The number and affinity of mu-opioid
receptors did not significantly differ between the 2 genotypes in any of
the brain regions examined. Differences in response to other G
protein-coupled receptor-directed drugs were not observed. Bohn et al.
(1999) suggested that their results provided evidence in vivo for the
physiologic importance of beta-arrestin-2 in regulating the function of
a specific G protein-coupled receptor, the mu-opioid receptor. Moreover,
they suggested that inhibition of beta-arrestin-2 function might lead to
enhanced analgesic effectiveness of morphine and provide potential new
avenues for the study and treatment of pain, narcotic tolerance, and
dependence.

Bohn et al. (2000) showed that in mice lacking beta-arrestin-2,
desensitization of the mu-opioid receptor does not occur after chronic
morphine treatment, and that these animals fail to develop
antinociceptive tolerance. However, the deletion of beta-arrestin-2 does
not prevent a chronic morphine-induced upregulation of adenylyl cyclase
activity, a cellular marker of dependence, and the mutant mice still
become physically dependent on the drug.

Lymphocyte chemotaxis is a complex process by which cells move within
tissues and across barriers such as vascular endothelium and is usually
stimulated by chemokines such as stromal cell-derived factor 1 (SDF1;
600835) acting via G protein-coupled receptors. Because members of this
receptor family are regulated (desensitized) by G protein-coupled
receptor kinase (GRK)-mediated receptor phosphorylation and
beta-arrestin binding, Fong et al. (2002) examined signaling and
chemotactic responses in splenocytes derived from knockout mice
deficient in various beta-arrestins and GRKs, with the expectation that
these responses might be enhanced. Knockouts of beta-arrestin-2, GPRK5
(600870), and GPRK6 (600869) were examined because all 3 proteins are
expressed at high levels in purified mouse CD3(+) T and B220(+) B
splenocytes. SDF1 stimulation of membrane GTPase activity was unaffected
in splenocytes derived from Grk5-deficient mice but was increased in
splenocytes from the beta-arrestin-2- and Grk6-deficient animals.
Surprisingly, however, both T and B cells from beta-arrestin-2-deficient
animals and T cells from Grk6-deficient animals were strikingly impaired
in their ability to respond to SDF1 both in transwell migration assays
and in transendothelial migration assays. Chemotactic responses of
lymphocytes from Grk5-deficient mice were unaffected. Thus, these
results indicated that beta-arrestin-2 and GPRK6 actually play positive
regulatory roles in mediating the chemotactic responses of T and B
lymphocytes to SDF1.

Wilbanks et al. (2004) showed that the functional knockdown of
beta-arrestin-2 in zebrafish embryos recapitulates the many phenotypes
of Hedgehog pathway mutants. Expression of wildtype beta-arrestin-2, or
constitutive activation of the Hedgehog pathway downstream of Smoothened
(SMO; 601500), rescues the phenotypes caused by beta-arrestin-2
deficiency. These results suggested to Wilbanks et al. (2004) that a
functional interaction between beta-arrestin-2 and Smo may be critical
to regulate Hedgehog signaling in zebrafish development.

BARR2 is crucial in transducing CXCR2 (146928)-mediated signals
associated with chemotaxis. Su et al. (2005) examined peritoneal
neutrophils from Barr2-deficient mice to assess Cxcr2 signaling activity
and observed increased Ca(2+) mobilization, superoxide anion production,
and GTPase activity, but decreased receptor internalization, compared
with wildtype mice. Both dorsal air pouch and excisional wound healing
models in Barr2 -/- mice showed increased neutrophil recruitment in
response to Cxcl1 (155730). Wound reepithelialization was also
significantly faster in mice lacking Barr2. Su et al. (2005) concluded
that BARR2 is a negative regulator of CXCR2 signaling.

Lithium, a pharmacologic agent used to treat psychiatric disorders, acts
by regulating GSK3 (see 606784)/AKT1 (164730) signaling. Beaulieu et al.
(2008) found that wildtype mice treated with lithium showed increased
phosphorylation/activation of Akt, resulting in
phosphorylation/inhibition of Gsk3b (605004) in the striatum. In
contrast, Barr2-null treated with lithium mice showed a minor reduction
in striatal phospho-Akt and no change in phospho-Gsk3b levels. Lithium
administration inhibited activity and decreased immobility in the tail
suspension test in wildtype mice, but had no behavioral effects on
Barr2-null mice. Further studies showed that Barr2 and PP2CA phosphatase
(PPP2CA; 176915) formed a complex, which inhibits AKT1 activation.
Beaulieu et al. (2008) postulated that lithium acts by destabilizing the
AKT1/PP2CA/BARR2 signaling complex, thereby enhancing the activation of
AKT1 and inhibition of GSK3B, which ultimately mediates behavioral
changes. Barr2-null mice that are unable to form this signaling complex
have a loss of indirect inhibition of Gsk3B and thus do not exhibit
behavioral responses to lithium. The findings suggested that BARR2 is an
important determinant of the regulation of behavior by lithium via G
protein-coupled receptors.

*FIELD* RF
1. Alloway, P. G.; Howard, L.; Dolph, P. J.: The formation of stable
rhodopsin-arrestin complexes induces apoptosis and photoreceptor cell
degeneration. Neuron 28: 129-138, 2000.

2. Attramadal, H.; Arriza, J. L.; Aoki, C.; Dawson, T. M.; Codina,
J.; Kwatra, M. M.; Snyder, S. H.; Caron, M. G.; Lefkowitz, R. J.:
Beta-arrestin-2, a novel member of the arrestin/beta-arrestin gene
family. J. Biol. Chem. 267: 17882-17890, 1992.

3. Beaulieu, J.-M.; Marion, S.; Rodriguiz, R. M.; Medvedev, I. O.;
Sotnikova, T. D.; Ghisi, V.; Wetsel, W. C.; Lefkowitz, R. J.; Gainetdinov,
R. R.; Caron, M. G.: A beta-arrestin 2 signaling complex mediates
lithium action on behavior. Cell 132: 125-136, 2008.

4. Bohn, L. M.; Gainetdinov, R. R.; Lin, F.-T.; Lefkowitz, R. J.;
Caron, M. G.: Mu-opioid receptor desensitization by beta-arrestin-2
determines morphine tolerance but not dependence. Nature 408: 720-723,
2000.

5. Bohn, L. M.; Lefkowitz, R. J.; Gainetdinov, R. R.; Peppel, K.;
Caron, M. G.; Lin, F.-T.: Enhanced morphine analgesia in mice lacking
beta-arrestin 2. Science 286: 2495-2498, 1999.

6. Calabrese, G.; Sallese, M.; Stornaiuolo, A.; Stuppia, L.; Palka,
G.; De Blasi, A.: Chromosome mapping of the human arrestin (SAG),
beta-arrestin 2 (ARRB2), and beta-adrenergic receptor kinase 2 (ADRBK2)
genes. Genomics 23: 286-288, 1994.

7. Chen, W.; Kirkbride, K. C.; How, T.; Nelson, C. D.; Mo, J.; Frederick,
J. P.; Wang, X.-F.; Lefkowitz, R. J.; Blobe, G. C.: Beta-arrestin
2 mediates endocytosis of type III TGF-beta receptor and down-regulation
of its signaling. Science 301: 1394-1397, 2003.

8. Chen, W.; Ren, X.-R.; Nelson, C. D.; Barak, L. S.; Chen, J. K.;
Beachy, P. A.; de Sauvage, F.; Lefkowitz, R. J.: Activity-dependent
internalization of Smoothened mediated by beta-arrestin 2 and GRK2. Science 306:
2257-2260, 2004.

9. Chen, W.; ten Berge, D.; Brown, J.; Ahn, S.; Hu, L. A.; Miller,
W. E.; Caron, M. G.; Barak, L. S.; Nusse, R.; Lefkowitz, R. J.: Dishevelled
2 recruits beta-arrestin 2 to mediate Wnt5A-stimulated endocytosis
of frizzled 4. Science 301: 1391-1394, 2003.

10. Coureuil, M.; Lecuyer, H.; Scott, M. G. H.; Boularan, C.; Enslen,
H.; Soyer, M.; Mikaty, G.; Bourdoulous, S.; Nassif, X.; Marullo, S.
: Meningococcus hijacks a beta-2-adrenoceptor/beta-arrestin pathway
to cross brain microvasculature endothelium. Cell 143: 1149-1160,
2010.

11. Fong, F. M.; Premont, R. T.; Richardson, R. M.; Yu, Y.-R. A.;
Lefkowitz, R. J.; Patel, D. D.: Defective lymphocyte chemotaxis in
beta-arrestin2- and GRK6-deficient mice. Proc. Nat. Acad. Sci. 99:
7478-7483, 2002.

12. Kiselev, A.; Socolich, M.; Vinos, J.; Hardy, R. W.; Zuker, C.
S.; Ranganathan, R.: A molecular pathway for light-dependent photoreceptor
apoptosis in Drosophila. Neuron 28: 139-152, 2000.

13. Kovacs, J. J.; Whalen, E. J.; Liu, R.; Xiao, K.; Kim, J.; Chen,
M.; Wang, J.; Chen, W.; Lefkowitz, R. J.: Beta-arrestin-mediated
localization of Smoothened to the primary cilium. Science 320: 1777-1781,
2008.

14. Luan, B.; Zhao, J.; Wu, H.; Duan, B.; Shu, G.; Wang, X.; Li, D.;
Jia, W.; Kang, J.; Pei, G.: Deficiency of a beta-arrestin-2 signal
complex contributes to insulin resistance. Nature 457: 1146-1149,
2009.

15. McDonald, P. H.; Chow, C.-W.; Miller, W. E.; Laporte, S. A.; Field,
M. E.; Lin, F.-T.; Davis, R. J.; Lefkowitz, R. J.: Beta-arrestin
2: a receptor-regulated MAPK scaffold for the activation of JNK3. Science 290:
1574-1577, 2000.

16. Shenoy, S. K.; McDonald, P. H.; Kohout, T. A.; Lefkowitz, R. J.
: Regulation of receptor fate by ubiquitination of activated beta-2-adrenergic
receptor and beta-arrestin. Science 294: 1307-1313, 2001.

17. Su, Y.; Raghuwanshi, S. K.; Yu, Y.; Nanney, L. B.; Richardson,
R. M.; Richmond, A.: Altered CXCR2 signaling in beta-arrestin-2-deficient
mouse models. J. Immun. 175: 5396-5402, 2005.

18. Wilbanks, A. M.; Fralish, G. B.; Kirby, M. L.; Barak, L. S.; Li,
Y.-X.; Caron, M. G.: Beta-arrestin 2 regulates zebrafish development
through the Hedgehog signaling pathway. Science 306: 2264-2267,
2004.

*FIELD* CN
Paul J. Converse - updated: 3/18/2011
Ada Hamosh - updated: 3/9/2009
Ada Hamosh - updated: 7/17/2008
Cassandra L. Kniffin - updated: 2/21/2008
Paul J. Converse - updated: 9/1/2006
Ada Hamosh - updated: 1/14/2005
Ada Hamosh - updated: 9/25/2003
Victor A. McKusick - updated: 6/17/2002
Ada Hamosh - updated: 11/30/2001
Ada Hamosh - updated: 12/14/2000
Ada Hamosh - updated: 12/1/2000
Ada Hamosh - updated: 12/22/1999

*FIELD* CD
Victor A. McKusick: 10/22/1992

*FIELD* ED
mgross: 03/22/2011
mgross: 3/22/2011
terry: 3/18/2011
alopez: 3/11/2009
terry: 3/9/2009
alopez: 7/21/2008
terry: 7/17/2008
wwang: 3/18/2008
ckniffin: 2/21/2008
carol: 12/26/2007
wwang: 5/15/2007
alopez: 5/1/2007
terry: 4/25/2007
mgross: 9/27/2006
terry: 9/1/2006
alopez: 1/18/2005
terry: 1/14/2005
terry: 7/19/2004
tkritzer: 9/30/2003
terry: 9/25/2003
cwells: 7/3/2002
terry: 6/21/2002
terry: 6/17/2002
alopez: 12/3/2001
terry: 11/30/2001
cwells: 1/29/2001
carol: 1/23/2001
cwells: 1/23/2001
cwells: 1/19/2001
terry: 12/14/2000
joanna: 12/4/2000
mgross: 12/1/2000
alopez: 12/27/1999
terry: 12/22/1999
terry: 11/7/1994
carol: 3/19/1994
carol: 10/22/1992

RBCC Red Blood Cell Collection

Full text data of ARRB2