Figure 2.

Inhibition of insulin signaling pathway by SOCS1 and SOCS3. SOCS1 and SOCS3 are induced by cytokines and involved in a negative feed-back loop. SOCS1 and SOCS3 also inhibit insulin signaling by different mechanisms. They interfere with the binding between the insulin receptor and IRS1/2 proteins. SOCS1 also inhibits the tyrosine kinase activity of the insulin receptor. Both SOCS1 and SOCS3 can interact with the tyrosine-phosphorylated IRS proteins leading to their degradation by the proteasome. The resulting effect is a decrease in the insulin-induced activation of the IRS1/2-PI3K-PKB axis leading to a reduction in the metabolic effects of insulin.