Suppressor of cytokine signaling 1

Identifiers

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	• nucleus • cytoplasm • cytosol • cytoplasmic membrane-bounded vesicle
Biological process	• regulation of protein phosphorylation • JAK-STAT cascade • regulation of activation of JAK2 kinase activity • protein ubiquitination • cytokine-mediated signaling pathway • organ regeneration • response to estradiol • response to lipopolysaccharide • response to progesterone • regulation of growth • response to drug • regulation of tyrosine phosphorylation of Stat1 protein • negative regulation of tyrosine phosphorylation of Stat3 protein • fat cell differentiation • negative regulation of JAK-STAT cascade • negative regulation of insulin receptor signaling pathway • regulation of cytokine secretion • interferon-gamma-mediated signaling pathway • regulation of interferon-gamma-mediated signaling pathway • type I interferon signaling pathway • regulation of type I interferon-mediated signaling pathway • JAK-STAT cascade involved in growth hormone signaling pathway • cellular response to amino acid stimulus • negative regulation of cyclin-dependent protein kinase activity
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 16:
11.25 – 11.26 Mb

Chr 16:
10.78 – 10.79 Mb

PubMed search

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 signalling (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), GM-CSF, and interferon-gamma (IFN-γ). 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-γ action, which is required for normal postnatal growth and survival.^[4]

Interactions

Suppressor of cytokine signaling 1 has been shown to interact with:

CD117,^[5]
Colony stimulating factor 1 receptor^[6]
Growth hormone receptor,^[7]
IRS2,^[8]
Janus kinase 2,^[9]^[10]^[11]^[12]^[13]^[14] and
TEC.^[15]

References

↑ Yoshimura A, Ohkubo T, Kiguchi T, Jenkins NA, Gilbert DJ, Copeland NG, Hara T, Miyajima A (August 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.
↑ Minamoto S, Ikegame K, Ueno K, Narazaki M, Naka T, Yamamoto H, Matsumoto T, Saito H, Hosoe S, Kishimoto T (September 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.
↑ "OrthoMaM phylogenetic marker: SOCS1 coding sequence".
↑ "Entrez Gene: SOCS1 suppressor of cytokine signaling 1".
↑ De Sepulveda P, Okkenhaug K, Rose JL, Hawley RG, Dubreuil P, Rottapel R (February 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.
↑ Bourette RP, De Sepulveda P, Arnaud S, Dubreuil P, Rottapel R, Mouchiroud G (June 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.
↑ Ram PA, Waxman DJ (Dec 1999). "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.
↑ Rui L, Yuan M, Frantz D, Shoelson S, White MF (November 2002). "SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2". J. Biol. Chem. 277 (44): 42394–8. doi:10.1074/jbc.C200444200. PMID 12228220.
↑ Yasukawa H, Misawa H, Sakamoto H, Masuhara M, Sasaki A, Wakioka T, Ohtsuka S, Imaizumi T, Matsuda T, Ihle JN, Yoshimura A (March 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.
↑ Dif F, Saunier E, Demeneix B, Kelly PA, Edery M (Dec 2001). "Cytokine-inducible SH2-containing protein suppresses PRL signaling by binding the PRL receptor". Endocrinology 142 (12): 5286–93. doi:10.1210/endo.142.12.8549. PMID 11713228.
↑ Endo TA, 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 (June 1997). "A new protein containing an SH2 domain that inhibits JAK kinases". Nature 387 (6636): 921–4. doi:10.1038/43213. PMID 9202126.
↑ Pezet A, Favre H, Kelly PA, Edery M (August 1999). "Inhibition and restoration of prolactin signal transduction by suppressors of cytokine signaling". J. Biol. Chem. 274 (35): 24497–502. doi:10.1074/jbc.274.35.24497. PMID 10455112.
↑ Ungureanu D, Saharinen P, Junttila I, Hilton DJ, Silvennoinen O (May 2002). "Regulation of Jak2 through the ubiquitin-proteasome pathway involves phosphorylation of Jak2 on Y1007 and interaction with SOCS-1". Mol. Cell. Biol. 22 (10): 3316–26. doi:10.1128/mcb.22.10.3316-3326.2002. PMC 133778. PMID 11971965.
↑ 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 (October 1997). "Cloning and characterization of novel CIS family genes". Biochem. Biophys. Res. Commun. 239 (2): 439–46. doi:10.1006/bbrc.1997.7484. PMID 9344848.
↑ Ohya Ki, Kajigaya S, Yamashita Y, Miyazato A, Hatake K, Miura Y, Ikeda U, Shimada K, Ozawa K, Mano H (October 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.

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, Nicola NA, Martin HM, Hilton DJ (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, Murray LJ, Rayner JR, Jenkins BJ, Gonda TJ, Alexander WS, Metcalf D, Nicola NA, Hilton DJ (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, 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 (1997). "A new protein containing an SH2 domain that inhibits JAK kinases". Nature 387 (6636): 921–4. doi:10.1038/43213. PMID 9202126.
Ohya Ki, Kajigaya S, Yamashita Y, Miyazato A, Hatake K, Miura Y, Ikeda U, Shimada K, Ozawa K, Mano H (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, Hawley RG, Dubreuil P, Rottapel R (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.
Zhang JG, Farley A, Nicholson SE, Willson TA, Zugaro LM, Simpson RJ, Moritz RL, Cary D, Richardson R, Hausmann G, Kile BJ, Kent SB, Alexander WS, Metcalf D, Hilton DJ, Nicola NA, Baca M (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.
Yasukawa H, Misawa H, Sakamoto H, Masuhara M, Sasaki A, Wakioka T, Ohtsuka S, Imaizumi T, Matsuda T, Ihle JN, Yoshimura A (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.
Marine JC, Topham DJ, McKay C, Wang D, Parganas E, Stravopodis D, Yoshimura A, Ihle JN (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, Ohashi H, Yoshimura A, Ohyashiki K (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, Yoshimura A, Leonard WJ (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, Kohzaki H, Morita Y, Narazaki M, Okumura K, Saitoh H, Nakagawa R, Uchiyama Y, Akira S, Kishimoto T (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.
Bourette RP, De Sepulveda P, Arnaud S, Dubreuil P, Rottapel R, Mouchiroud G (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, Inamdar N, Boivin LM, Shang Y, Furlanetto RW (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, Nemes C, Cavarretta IT, Puhr M, Steiner H, Minelli A, Bartsch G, Offner F, Hobisch A, Doppler W, Culig Z (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.
Neuwirt H, Puhr M, Santer FR, Susani M, Doppler W, Marcias G, Rauch V, Brugger M, Hobisch A, Kenner L, Culig Z (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.

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

JAK-STAT signaling pathway

Ligand

Cytokine

Cytokine receptor

Janus kinase

Adaptor proteins

STAT	STAT1 STAT2 STAT3 STAT4 STAT5 STAT6

PIAS	PIAS1 PIAS2 PIAS3 PIAS4

SOCS	1 2 3 4 5 6 7 CISH

IRF	IRF1 IRF2 IRF3 IRF4 IRF5 IRF6 IRF7 IRF8

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Suppressor of cytokine signaling 1

See also

Interactions

References

Further reading