Suppressors of cytokine signaling: Relevance to gastrointestinal function and disease

AbstractBackground & Aims: The suppressor of cytokine signaling (SOCS) proteins are a family of Src homology 2 domain-containing proteins. Currently, there are 8 members of the SOCS family, of which a number have been implicated strongly in the negative regulation of cytokine signal transduction pathways. Methods: This review focuses on recent discoveries about 4 SOCS family members, SOCS-1, -2, and -3, and cytokine-inducible SH2-domain containing (CIS), and provides more limited information about other SOCS family members. Results: A large number of cytokines and growth factors are now known to induce SOCS proteins. In turn, SOCS inhibit the actions of a growing number of cytokines and growth factors in vitro or in vivo. SOCS proteins exert their inhibitory effects at the level of activation of janus kinases (JAKs) or by competing with transcription factors for binding sites on activated cytokine receptors. SOCS proteins also may mediate the ubiquitination and subsequent degradation of the SOCS protein and its bound signaling complex. Genetic modification of SOCS genes in mice has revealed crucial roles in the negative regulation of a number of important physiologic parameters including interferon γ activity, growth, blood cell production, and placental development. Conclusions: Information about SOCS action in gastrointestinal function and disease is only just emerging, but available data indicate a role in growth of gastrointestinal tissues, inflammatory bowel disease, and cancer.GASTROENTEROLOGY 2002;123:2064-208