Suppressor of cytokine signaling 1

Suppressor of cytokine signaling 1
Identifiers
Symbols	SOCS1; CIS1; CISH1; JAB; SOCS-1; SSI-1; SSI1; TIP3
External IDs	OMIM: 603597 MGI: 1354910 HomoloGene: 2776 GeneCards: SOCS1 Gene
Gene Ontology Molecular function • protein kinase inhibitor activity • insulin-like growth factor receptor binding • protein binding • kinase inhibitor activity • protein kinase binding Cellular component • cytoplasm • cytosol Biological process • regulation of protein phosphorylation • JAK-STAT cascade • cytokine-mediated signaling pathway • cytokine-mediated signaling pathway • organ regeneration • response to estradiol stimulus • response to lipopolysaccharide • response to progesterone stimulus • response to cytokine stimulus • intracellular signal transduction • regulation of growth • response to drug • negative regulation of tyrosine phosphorylation of Stat3 protein • response to peptide hormone stimulus • fat cell differentiation • negative regulation of JAK-STAT cascade • negative regulation of JAK-STAT cascade • negative regulation of insulin receptor signaling pathway • interferon-gamma-mediated signaling pathway • regulation of interferon-gamma-mediated signaling pathway • type I interferon-mediated signaling pathway • regulation of type I interferon-mediated signaling pathway Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	8651	12703
Ensembl	ENSG00000185338	ENSMUSG00000038037
UniProt	O15524	O35716
RefSeq (mRNA)	NM_003745	NM_009896.2
RefSeq (protein)	NP_003736	NP_034026.1
Location (UCSC)	Chr 16: 11.35 – 11.35 Mb	Chr 16: 10.78 – 10.79 Mb
PubMed search	[1]	[2]

Suppressor of cytokine signaling 1 is a protein that in humans is encoded by the SOCS1 gene.^[1][2] SOCS1 orthologs ^[3] have been identified in several mammals for which complete genome data are available.

This gene encodes a member of the STAT-induced STAT inhibitor (SSI), also known as suppressor of cytokine signaling (SOCS), family. SSI family members are cytokine-inducible negative regulators of cytokine signaling. The expression of this gene can be induced by a subset of cytokines, including IL2, IL3 erythropoietin (EPO), CSF2/GM-CSF, and interferon (IFN)-gamma. The protein encoded by this gene functions downstream of cytokine receptors, and takes part in a negative feedback loop to attenuate cytokine signaling. Knockout studies in mice suggested the role of this gene as a modulator of IFN-gamma action, which is required for normal postnatal growth and survival.^[4]

See also

• SOCS
• JAK-STAT signaling pathway

Interactions

Suppressor of cytokine signaling 1 has been shown to interact with Janus kinase 2,^{[5][6][7][8][9][10]} Growth hormone receptor,^[11] CD117,^[12] IRS2,^[13] Colony stimulating factor 1 receptor^[14] and TEC.^[15]

References

1. ^ Yoshimura A, Ohkubo T, Kiguchi T, Jenkins NA, Gilbert DJ, Copeland NG, Hara T, Miyajima A (Aug 1995). "A novel cytokine-inducible gene CIS encodes an SH2-containing protein that binds to tyrosine-phosphorylated interleukin 3 and erythropoietin receptors". EMBO J 14 (12): 2816–26. PMC 398400. PMID 7796808. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=398400. 
2. ^ Minamoto S, Ikegame K, Ueno K, Narazaki M, Naka T, Yamamoto H, Matsumoto T, Saito H, Hosoe S, Kishimoto T (Sep 1997). "Cloning and functional analysis of new members of STAT induced STAT inhibitor (SSI) family: SSI-2 and SSI-3". Biochem Biophys Res Commun 237 (1): 79–83. doi:10.1006/bbrc.1997.7080. PMID 9266833. 
3. ^ "OrthoMaM phylogenetic marker: SOCS1 coding sequence". http://www.orthomam.univ-montp2.fr/orthomam/data/cds/detailMarkers/ENSG00000185338_SOCS1.xml. 
4. ^ "Entrez Gene: SOCS1 suppressor of cytokine signaling 1". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8651. 
5. ^ Yasukawa, H; Misawa H, Sakamoto H, Masuhara M, Sasaki A, Wakioka T, Ohtsuka S, Imaizumi T, Matsuda T, Ihle J N, Yoshimura A (Mar. 1999). "The JAK-binding protein JAB inhibits Janus tyrosine kinase activity through binding in the activation loop". EMBO J. (ENGLAND) 18 (5): 1309–20. doi:10.1093/emboj/18.5.1309. ISSN 0261-4189. PMC 1171221. PMID 10064597. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1171221. 
6. ^ Dif, F; Saunier E, Demeneix B, Kelly P A, Edery M (Dec. 2001). "Cytokine-inducible SH2-containing protein suppresses PRL signaling by binding the PRL receptor". Endocrinology (United States) 142 (12): 5286–93. doi:10.1210/en.142.12.5286. ISSN 0013-7227. PMID 11713228. 
7. ^ Endo, T A; Masuhara M, Yokouchi M, Suzuki R, Sakamoto H, Mitsui K, Matsumoto A, Tanimura S, Ohtsubo M, Misawa H, Miyazaki T, Leonor N, Taniguchi T, Fujita T, Kanakura Y, Komiya S, Yoshimura A (Jun. 1997). "A new protein containing an SH2 domain that inhibits JAK kinases". Nature (ENGLAND) 387 (6636): 921–4. doi:10.1038/43213. ISSN 0028-0836. PMID 9202126. 
8. ^ Pezet, A; Favre H, Kelly P A, Edery M (Aug. 1999). "Inhibition and restoration of prolactin signal transduction by suppressors of cytokine signaling". J. Biol. Chem. (UNITED STATES) 274 (35): 24497–502. doi:10.1074/jbc.274.35.24497. ISSN 0021-9258. PMID 10455112. 
9. ^ Ungureanu, Daniela; Saharinen Pipsa, Junttila Ilkka, Hilton Douglas J, Silvennoinen Olli (May. 2002). "Regulation of Jak2 through the Ubiquitin-Proteasome Pathway Involves Phosphorylation of Jak2 on Y1007 and Interaction with SOCS-1". Mol. Cell. Biol. (United States) 22 (10): 3316–26. doi:10.1128/MCB.22.10.3316-3326.2002. ISSN 0270-7306. PMC 133778. PMID 11971965. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=133778. 
10. ^ Masuhara, M; Sakamoto H, Matsumoto A, Suzuki R, Yasukawa H, Mitsui K, Wakioka T, Tanimura S, Sasaki A, Misawa H, Yokouchi M, Ohtsubo M, Yoshimura A (Oct. 1997). "Cloning and characterization of novel CIS family genes". Biochem. Biophys. Res. Commun. (UNITED STATES) 239 (2): 439–46. doi:10.1006/bbrc.1997.7484. ISSN 0006-291X. PMID 9344848. 
11. ^ Ram, P A; Waxman D J (Dec. 1999). "SOCS/CIS protein inhibition of growth hormone-stimulated STAT5 signaling by multiple mechanisms". J. Biol. Chem. (UNITED STATES) 274 (50): 35553–61. doi:10.1074/jbc.274.50.35553. ISSN 0021-9258. PMID 10585430. 
12. ^ De Sepulveda, P; Okkenhaug K, Rose J L, Hawley R G, Dubreuil P, Rottapel R (Feb. 1999). "Socs1 binds to multiple signalling proteins and suppresses steel factor-dependent proliferation". EMBO J. (ENGLAND) 18 (4): 904–15. doi:10.1093/emboj/18.4.904. ISSN 0261-4189. PMC 1171183. PMID 10022833. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1171183. 
13. ^ Rui, Liangyou; Yuan Minsheng, Frantz Daniel, Shoelson Steven, White Morris F (Nov. 2002). "SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2". J. Biol. Chem. (United States) 277 (44): 42394–8. doi:10.1074/jbc.C200444200. ISSN 0021-9258. PMID 12228220. 
14. ^ Bourette, R P; De Sepulveda P, Arnaud S, Dubreuil P, Rottapel R, Mouchiroud G (Jun. 2001). "Suppressor of cytokine signaling 1 interacts with the macrophage colony-stimulating factor receptor and negatively regulates its proliferation signal". J. Biol. Chem. (United States) 276 (25): 22133–9. doi:10.1074/jbc.M101878200. ISSN 0021-9258. PMID 11297560. 
15. ^ Ohya, K i; Kajigaya S, Yamashita Y, Miyazato A, Hatake K, Miura Y, Ikeda U, Shimada K, Ozawa K, Mano H (Oct. 1997). "SOCS-1/JAB/SSI-1 can bind to and suppress Tec protein-tyrosine kinase". J. Biol. Chem. (UNITED STATES) 272 (43): 27178–82. doi:10.1074/jbc.272.43.27178. ISSN 0021-9258. PMID 9341160. 

Further reading

• Krebs DL, Hilton DJ (2001). "SOCS proteins: negative regulators of cytokine signaling". Stem Cells 19 (5): 378–87. doi:10.1634/stemcells.19-5-378. PMID 11553846. 
• Wang J, Campbell IL (2002). "Cytokine signaling in the brain: putting a SOCS in it?". J. Neurosci. Res. 67 (4): 423–7. doi:10.1002/jnr.10145. PMID 11835308. 
• Kile BT, Schulman BA, Alexander WS, et al. (2002). "The SOCS box: a tale of destruction and degradation". Trends Biochem. Sci. 27 (5): 235–41. doi:10.1016/S0968-0004(02)02085-6. PMID 12076535. 
• Starr R, Willson TA, Viney EM, et al. (1997). "A family of cytokine-inducible inhibitors of signalling". Nature 387 (6636): 917–21. doi:10.1038/43206. PMID 9202125. 
• Endo TA, Masuhara M, Yokouchi M, et al. (1997). "A new protein containing an SH2 domain that inhibits JAK kinases". Nature 387 (6636): 921–4. doi:10.1038/43213. PMID 9202126. 
• Ohya K, Kajigaya S, Yamashita Y, et al. (1997). "SOCS-1/JAB/SSI-1 can bind to and suppress Tec protein-tyrosine kinase". J. Biol. Chem. 272 (43): 27178–82. doi:10.1074/jbc.272.43.27178. PMID 9341160. 
• Dey BR, Spence SL, Nissley P, Furlanetto RW (1998). "Interaction of human suppressor of cytokine signaling (SOCS)-2 with the insulin-like growth factor-I receptor". J. Biol. Chem. 273 (37): 24095–101. doi:10.1074/jbc.273.37.24095. PMID 9727029. 
• De Sepulveda P, Okkenhaug K, Rose JL, et al. (1999). "Socs1 binds to multiple signalling proteins and suppresses steel factor-dependent proliferation". EMBO J. 18 (4): 904–15. doi:10.1093/emboj/18.4.904. PMC 1171183. PMID 10022833. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1171183. 
• Zhang JG, Farley A, Nicholson SE, et al. (1999). "The conserved SOCS box motif in suppressors of cytokine signaling binds to elongins B and C and may couple bound proteins to proteasomal degradation". Proc. Natl. Acad. Sci. U.S.A. 96 (5): 2071–6. doi:10.1073/pnas.96.5.2071. PMC 26738. PMID 10051596. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=26738. 
• Yasukawa H, Misawa H, Sakamoto H, et al. (1999). "The JAK-binding protein JAB inhibits Janus tyrosine kinase activity through binding in the activation loop". EMBO J. 18 (5): 1309–20. doi:10.1093/emboj/18.5.1309. PMC 1171221. PMID 10064597. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1171221. 
• Marine JC, Topham DJ, McKay C, et al. (1999). "SOCS1 deficiency causes a lymphocyte-dependent perinatal lethality". Cell 98 (5): 609–16. doi:10.1016/S0092-8674(00)80048-3. PMID 10490100. 
• Yandava CN, Pillari A, Drazen JM (1999). "Radiation hybrid and cytogenetic mapping of SOCS1 and SOCS2 to chromosomes 16p13 and 12q, respectively". Genomics 61 (1): 108–11. doi:10.1006/geno.1999.5937. PMID 10512686. 
• Okabe S, Tauchi T, Morita H, et al. (1999). "Thrombopoietin induces an SH2-containing protein, CIS1, which binds to Mpl: involvement of the ubiquitin proteosome pathway". Exp. Hematol. 27 (10): 1542–7. doi:10.1016/S0301-472X(99)00094-6. PMID 10517496. 
• Ram PA, Waxman DJ (2000). "SOCS/CIS protein inhibition of growth hormone-stimulated STAT5 signaling by multiple mechanisms". J. Biol. Chem. 274 (50): 35553–61. doi:10.1074/jbc.274.50.35553. PMID 10585430. 
• Sporri B, Kovanen PE, Sasaki A, et al. (2001). "JAB/SOCS1/SSI-1 is an interleukin-2-induced inhibitor of IL-2 signaling". Blood 97 (1): 221–6. doi:10.1182/blood.V97.1.221. PMID 11133764. 
• Kawazoe Y, Naka T, Fujimoto M, et al. (2001). "Signal Transducer and Activator of Transcription (Stat)-Induced Stat Inhibitor 1 (Ssi-1)/Suppressor of Cytokine Signaling 1 (Socs1) Inhibits Insulin Signal Transduction Pathway through Modulating Insulin Receptor Substrate 1 (Irs-1) Phosphorylation". J. Exp. Med. 193 (2): 263–9. doi:10.1084/jem.193.2.263. PMC 2193341. PMID 11208867. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2193341. 
• Bourette RP, De Sepulveda P, Arnaud S, et al. (2001). "Suppressor of cytokine signaling 1 interacts with the macrophage colony-stimulating factor receptor and negatively regulates its proliferation signal". J. Biol. Chem. 276 (25): 22133–9. doi:10.1074/jbc.M101878200. PMID 11297560. 
• Mooney RA, Senn J, Cameron S, et al. (2001). "Suppressors of cytokine signaling-1 and -6 associate with and inhibit the insulin receptor. A potential mechanism for cytokine-mediated insulin resistance". J. Biol. Chem. 276 (28): 25889–93. doi:10.1074/jbc.M010579200. PMID 11342531. 
• Bellezza I, Neuwirt H, et al. (2006). "Suppressor of Cytokine Signaling-3 Antagonizes cAMP Effects on Proliferation and Apoptosis and Is Expressed in Human Prostate Cancer". American Journal of Pathology 169 (6): 2199–2208. doi:10.2353/ajpath.2006.060171. PMC 1762483. PMID 17148681. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1762483. 
• Neuwirt H, Puhr M, et al. (2009). "Suppressor of Cytokine Signaling (SOCS)-1 Is Expressed in Human Prostate Cancer and Exerts Growth-Inhibitory Function through Down-Regulation of Cyclins and Cyclin-Dependent Kinases". American Journal of Pathology 174 (5): 921–1930. doi:10.2353/ajpath.2009.080751. PMC 2671279. PMID 19342366. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2671279. 

This article incorporates text from the United States National Library of Medicine, which is in the public domain.