Adaptor Protein Insulin Receptor

Here we present the crystal structure of the aps sh2 domain in complex with the phosphorylated tyrosine kinase domain of the insulin.

Adaptor protein insulin receptor. Structural basis for recruitment of the adaptor protein aps to the activated insulin receptor. Of the 90 unique tyrosine kinase genes identified in the. Hu j liu j ghirlando r saltiel ar hubbard sr. This review will focus on key signaling intermediates of the ir and igf 1r the insulin receptor substrate irs proteins with an emphasis on irs 2 and discuss how these adaptor proteins play a pivotal role at the intersection of metabolism and cancer.

The adaptor protein aps is a substrate of the insulin receptor and couples receptor activation with phosphorylation of cbl to facilitate glucose uptake. Iii c 2 insulin receptor tyrosine kinase activity. Most but not all investigators have found reduced tyrosine kinase. Among the proteins recruited for activation of downstream signaling pathways are several adaptor non enzymatic proteins including the insulin receptor substrate irs proteins shc and sh2b2 aps.

Il 4 and il 13 contribute to allergic lung inflammation. Mandarino in encyclopedia of hormones 2003. Much of the specificity of signal transduction depends on the recruitment of several signalling components such as protein kinases and g protein gtpases into short lived active complexes in response to an activating signal such as a growth factor binding to its receptor. Insulin receptor substrate 2 irs2 is an adaptor protein that becomes tyrosine phosphorylated in response to the cytokines interleukin 4 il 4 and il 13 which results in activation of the phosphoinositide 3 kinase pi3k akt pathway.

Metabolically the insulin receptor plays a key role in the regulation of glucose homeostasis a functional process that under degenerate conditions may result in a range of clinical manifestations including diabetes and cancer. Insulin receptor tyrosine kinase activity has been examined in a variety of cell types skeletal muscle adipocytes hepatocytes and erythrocytes from normal weight and obese diabetic subjects. The insulin receptor substrate irs proteins are cytoplasmic adaptor proteins that function as essential signaling intermediates downstream of activated cell surface receptors many of which have. Crystal structure of the activated insulin receptor tyrosine kinase in complex with peptide substrate and atp analog.

Receptor tyrosine kinases rtks are the high affinity cell surface receptors for many polypeptide growth factors cytokines and hormones. The interaction with the activated insulin receptor is mediated by the src homology 2 sh2 domain of aps.