Regulation of cytokine signaling by the SOCS and Spred family proteins.

Various cytokines are involved in the regulation of the immune system and of hematopoiesis. Most cytokines utilize the so-called JAK-STAT pathway, but others activate the Ras-ERK pathway, which is more important than the STAT pathway for the proliferation of hematopoietic cells. Dysregulation of cytokine signaling can cause a variety of diseases, including allergy, inflammation, and cancer. We have identified two important regulator families involved in cytokine signaling: the SOCS proteins and the Spred proteins. Suppressors of cytokine signaling (SOCS) proteins bind to JAK and to certain receptors, thereby suppressing further signaling events. Spred family proteins interact with Ras and Raf, thereby suppressing ERK activation. Studies have shown that SOCS and Spred proteins are key physiological regulators of immunity, hematopoiesis, and angiogenesis. Evidence is also emerging for the involvement of these proteins in human diseases.