Regulation of cytokine receptor signaling by SOCS1.

The suppressor of cytokine signaling (SOCS) family of proteins is a novel class of negative feedback regulators of cytokine receptor signaling. SOCS1 is rapidly induced following stimulation by several type I and type II cytokines, and it attenuates their signaling by its ability to bind and inhibit all four of the Janus family of intracellular tyrosine kinases (JAKs). Studies from our own and other laboratories have documented another important function of SOCS1 in facilitating ubiquitination of protein substrates and their subsequent proteasomal degradation. SOCS1 also functions as a potential tumor suppressor by inhibiting several hematopoietic oncogenes. In addition to these negative regulatory functions, we have recently shown a positive regulatory role for SOCS1 in increasing the stability of major histocompatibility complex (MHC) class II proteins by preventing their degradation. These findings illustrate multiple roles for SOCS1 in cytokine receptor signaling, and provide groundwork for detailed analysis of the role of SOCS1 in pre-T cell receptor (TCR) and TCR signaling, and regulation of T helper (Th)1 and Th2 differentiation.