IRS1
IRS1 (insulin receptor substrate 1, also known as HIRS-1) is a cytoplasmic and nuclear signalling adapter protein. It relays signals from the insulin receptor and the insulin-like growth factor I receptor to downstream pathways that control growth and glucose and lipid metabolism. Browse Assay Genie's current range of IRS1 research reagents below, or read on for the biology behind the target.
IRS1 is a signalling adapter that participates in signal transduction from two prominent receptor tyrosine kinases, the insulin receptor (INSR) and the insulin-like growth factor I receptor (IGF1R). Through these receptors it plays an important role in development, growth, glucose homeostasis and lipid metabolism. Once phosphorylated by the insulin receptor, IRS1 acts as a signalling scaffold and propagates insulin action by binding SH2 domain-containing proteins, including the p85 regulatory subunit of PI3K, NCK1, NCK2, GRB2 and SHP2.
Different binding partners direct different outputs. Recruitment of GRB2 leads to activation of the guanine nucleotide exchange factor SOS1, which triggers the Ras/Raf/MEK/MAPK cascade. This cascade is involved in regulating gene expression and, in cooperation with the PI3K pathway, regulates cell growth and differentiation. Activation of the PI3K/AKT pathway is responsible for most of the metabolic effects of insulin in the cell. IRS1 also acts as a positive regulator of the Wnt/beta-catenin pathway by suppressing autophagy-mediated degradation of DVL2, which leads to cell proliferation.
The human IRS1 gene encodes a protein that is phosphorylated by the insulin receptor tyrosine kinase. HGNC places it in the insulin receptor substrate family and among pleckstrin homology domain containing proteins. According to the NCBI Gene summary, mutations in the gene are associated with type II diabetes and susceptibility to insulin resistance. Mouse and rat both have an Irs1 ortholog. UniProt records the protein in the cytoplasm and the nucleus.
IRS1 is phosphorylated by the insulin receptor and scaffolds downstream signalling, making it central to studies of how insulin action is propagated.
As a mediator of INSR and IGF1R signalling, IRS1 contributes to glucose homeostasis and lipid metabolism.
Mutations in the IRS1 gene are associated with type II diabetes and susceptibility to insulin resistance.
IRS1 links PI3K/AKT and Ras/MAPK signalling to cell growth and differentiation, and supports Wnt/beta-catenin signalling by protecting DVL2.
IRS1 is a signalling adapter for the insulin receptor and IGF1R. After phosphorylation it acts as a scaffold for SH2 domain proteins such as the p85 subunit of PI3K, GRB2, NCK1, NCK2 and SHP2, driving PI3K/AKT and Ras/MAPK signalling that regulate metabolism, growth and differentiation.
The approved HGNC name is insulin receptor substrate 1, and the symbol is IRS1. HIRS-1 is a recorded alias. UniProt lists the protein name as insulin receptor substrate 1, and the gene sits in the insulin receptor substrate family alongside IRS2 and IRS4.
The NCBI Gene summary associates IRS1 mutations with type II diabetes and susceptibility to insulin resistance. Mouse and rat each have an Irs1 ortholog, so the gene can be studied in rodent models; check the datasheet of any product for its validated reactivity.
Other members of the insulin receptor substrate family that act alongside IRS1 in receptor tyrosine kinase signalling.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P35568; product specifications from Assay Genie datasheets.