BACKGROUND SOCS1 (Suppressor of cytokine signaling 1) is a member of the STAT-induced STAT inhibitor (SSI), also known as suppressor of cytokine signaling (SOCS), family. These family members are characterized by the presence of a src homology (SH2) domain and a carboxyl-terminal conserved domain called the SOCS box. So far, 8 members of the SOCS family have been identified, termed SOCS-1 to SOCS-7 and CIS (cytokine-inducible SH2-containing protein).1 SOCS1 inhibits JAK-mediated cytokine signaling by binding to JAKs. It has been shown to be an important physiological negative regulator of various cytokines including IFNγ and IL-4. SOCS1 also modulates toll-like receptor (TLR) signaling in macrophages. SOCS1-deficient mice (SOCS1−/−) die neonatally because of multiorgan inflammation.2 Recently, it was demonstrated that SOCS1 also participated in downstream signaling of receptor tyrosine kinase such as c-Kit and insulin receptor.3 In addition, SOCS1 has also been suggested to function as an antioncogene. Mutations and deletions of the SOCS1 gene have been found in several lymphomas.4
1. Yasukawa H et al.: Ann. Rev. Immunol. 18:143-164, 2000.
2. Starr R et al.: Proc. Natl. Acad. Sci USA 95:14395-14399, 1998.
3. De Sepulveda P et al.: EMBO J. 18:904-915, 1999.
4. Calabrese V et al.: Mol. Cell 36:754-767, 2009.
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