The Suppressor of Cytokine Signaling (SOCS) family of proteins acts in a classic negative feedback loop to regulate cytokine signal transduction. Socs genes are induced by cytokines to express SOCS proteins, which then inhibit cytokine-induced signaling. SOCS-3, also known as CIS3 or SSI3, inhibits cytokine signaling by multiple cytokines and hormones, including Epo, prolactin, growth hormone (GH), IL-2, IL-3, IL-6, IL-11, leptin, ciliary neurotrophic factor, MCSF, and LIF. The SH2 domain of SOCS-3 also interacts with the cytoplasmic domains of phosphorylated GH receptor, leptin receptor, IGF-I receptor, and the gp130 common receptor subunit. SOCS-3 directly inhibits JAK2 catalytic activity, and silencing of SOCS-3 by methylation may be an important mechanism of constitutive activation of the JAK/STAT pathway in cancer pathogenesis.Synonyms: CIS-3, Cytokine-inducible SH2 protein 3, SOCS-3, SSI-3, SSI3, STAT-induced STAT inhibitor 3, Suppressor of cytokine signaling 3