IRS1

Insulin receptor substrate 1 (IRS-1) plays a key role in transmitting signals from the insulin and insulin-like growth factor-1 (IGF-1) receptors to intracellular pathways PI3K / Akt and Erk MAP kinase pathways.

Tyrosine phosphorylation of the insulin or IGF-1 receptors upon ligand binding induces the binding of IRS-1 through its SH2 homology domains. It is then itself tyrosine phosphorylated at numerous residues by these receptors, which enables it to activate several signalling pathways, including the PI3K pathway and the MAP kinase pathway.

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.

Regulation of IRS-1
The cellular protein levels of IRS-1 are regulated by the Cullin7 E3 ubiquin ligase, which targets IRS-1 for ubiquitin mediated degradation by the proteasome.