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Insulin receptor substrate 1 (IRS-1) is a protein that in humans is encoded by the IRS-1 gene.


Insulin receptor substrate 1 plays a key role in transmitting signals from the insulin and insulin-like growth factor-1 (IGF-1) receptor 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. Multiple tyrosine residues of IRS-1 itself are then phosphorylated by these receptors. This enables IRS-1 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 deficient 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.


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


IRS1 has been shown to interact with PTPN11,<ref...
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