Insulin Receptor Substrate 1 (IRS1)

Insulin receptor substrate 1 plays a key role in transmitting signals from the IGF-1 receptors to intracellular pathways PI3K / Akt and Erk MAP kinase pathways. Tyrosine phosphorylation of the insulin receptors or IGF-1 receptors, upon extracellular ligand binding, induces the cytoplasmic binding of IRS-1 to these receptors, through its SH2 domains.

IRS-1 plays important biological function for both metabolic and mitogenic (growth promoting) pathways: mice deficent of IRS1 have only a mild diabetic phenotype, but a pronounced growth impairment, i.e. IRS-1 knockout mice only reach 50% of the weight of normal mice. IRS-1 may also play a role in cancer, as it has been shown that transgenic mice overexpressing IRS-1 develop breast cancer.