Suppressor of cytokine signaling 3 (SOCS3 orSOCS-3) is aprotein that in humans is encoded by theSOCS3gene.[5][6] This gene encodes a member of the STAT-inducedSTAT 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 SOCS3 gene is induced by various cytokines, including IL6, IL10, and interferon (IFN)-gamma.
For signaling of IL-6, Epo, GCSF and Leptin, binding of SOCS3 to the respective cytokine receptor has been found to be crucial for the inhibitory function of SOCS3.
SOCS3 contributes to bothleptin resistance and insulin resistance as a result of increasedceramide synthesis.[11] For that reason, studies have shown that removal of the SOCS gene prevents against insulin resistance inobesity[10]
Studies of the mouse counterpart of this gene suggested the roles of this gene in the negative regulation of fetal liverhematopoiesis, and placental development.[12]
The SOCS3 protein can bind toJAK2 kinase, and inhibits the activity of JAK2 kinase.
^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^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.PMID9266833.
^abMasuhara 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 (November 1997). "Cloning and characterization of novel CIS family genes".Biochem Biophys Res Commun.239 (2):439–46.doi:10.1006/bbrc.1997.7484.PMID9344848.
^Cacalano NA, Sanden D, Johnston JA (May 2001). "Tyrosine-phosphorylated SOCS-3 inhibits STAT activation but binds to p120 RasGAP and activates Ras".Nat. Cell Biol.3 (5):460–5.doi:10.1038/35074525.PMID11331873.S2CID19179597.
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.PMID12076535.
Cookson WO, Ubhi B, Lawrence R, Abecasis GR, Walley AJ, Cox HE, Coleman R, Leaves NI, Trembath RC, Moffatt MF, Harper JI (2001). "Genetic linkage of childhood atopic dermatitis to psoriasis susceptibility loci".Nat. Genet.27 (4):372–3.doi:10.1038/86867.PMID11279517.S2CID22665448.
Cacalano NA, Sanden D, Johnston JA (2001). "Tyrosine-phosphorylated SOCS-3 inhibits STAT activation but binds to p120 RasGAP and activates Ras".Nat. Cell Biol.3 (5):460–5.doi:10.1038/35074525.PMID11331873.S2CID19179597.
Bode JG, Ludwig S, Freitas CA, Schaper F, Ruhl M, Melmed S, Heinrich PC, Häussinger D (2002). "The MKK6/p38 mitogen-activated protein kinase pathway is capable of inducing SOCS3 gene expression and inhibits IL-6-induced transcription".Biol. Chem.382 (10):1447–53.doi:10.1515/BC.2001.178.PMID11727828.S2CID31128727.
