IRS-1 substrate – Growth Factors and Cytokines

Insulin receptor (IR) substrate 1 (IRS-1) peptide is a highly selective substrate for certain kinase sub-families- such as receptor tyrosine kinases (which includes IR). IRS-1 is also a very good substrate for the cytoplasmic kinases JAK-1, 2, and 3. IRS-1 is a large ubiquitously expressed protein, vital for propagating insulin action. IRS-1 is activated by phosphorylation of multiple tyrosine residues via an activated IR. Activated IRS-1 then acts as a docking site for downstream signalling proteins which contain a Src homology 2 (SH2) domain (such as phosphatidylinositol 3-kinase (PI3K), growth factor receptor-bound protein 2 (Grb2), and SHP-2). In addition to its role in metabolic signalling, IRS-1 also propagates proliferative and anti-apoptotic signals and is overexpressed in most cancers.

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