IRS1

Insulin receptor substrate 1 (IRS-1) is a signalling adapter is_associated_with::protein that in humans is encoded by the IRS-1 is_associated_with::gene. It contains a single is_associated_with::pleckstrin homology (PH) domain at the N-terminus and a PTB domain ca. 40 residues downstream of this. Together with is_associated_with::IRS2, IRS3 (pseudogene) and is_associated_with::IRS4, it is homologous to the is_associated_with::Drosophila protein chico, whose disruption extends the median lifespan of flies up to 48%. Similarly, Irs1 mutant mice experience moderate life extension and delayed age-related pathologies.

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

is_associated_with::Tyrosine is_associated_with::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 is_associated_with::PTB 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 is_associated_with::metabolic and is_associated_with::mitogenic (growth promoting) pathways: mice deficient of IRS1 have only a mild diabetic is_associated_with::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 is_associated_with::transgenic mice overexpressing IRS-1 develop breast cancer.

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

Interactions
IRS1 has been shown to interact with:


 * is_associated_with::Bcl-2,
 * is_associated_with::Grb2,
 * INSR,
 * IGF1R,
 * JAK1,
 * JAK2,
 * is_associated_with::MAPK8,
 * is_associated_with::PIK3R1
 * is_associated_with::PIK3R3,
 * is_associated_with::PTK2,
 * is_associated_with::PTPN11,
 * is_associated_with::PTPN1,  and
 * is_associated_with::YWHAE.