PathwayStep5061 PathwayStep5060 PathwayStep5059 Dissociation of IRS-P from insulin receptor Binding of IRS to insulin receptor Phosphorylation of IRS IRS activation Authored: 2003-07-28 10:05:14 Reactome Database ID Release 4374713 Reactome, http://www.reactome.org ReactomeREACT_570 Using receptor mutagenesis studies it is known that IRS1 via its PTB domain binds to the insulin receptor at the juxtamembrane region at tyrosine 972. The interaction is further stabilized by the PH domain of IRS1 which interacts with the phospholipids of the plasma membrane. This allows the receptor to phosphorylate IRS1 on up to 13 of its tyrosine residues. Once phosphorylated the IRS1 falls away from the receptor. (Other IRS family members can also be phosphorylated by the insulin receptor - will be added in the near future.) Now in a tyrosine phosphorylated and hence activated state other proteins can interact with the IRS proteins.