IRS-1, or insulin receptor substrate 1, is the major substrate of the insulin receptor. It is thought to interact with the receptor itself, a process which is completely dependent upon receptor tyrosine kinase activity. When phosphorylated by the insulin receptor, IRS-1 binds specifically to cellular proteins that contain SH2 domains, such as phosphatidylinositol 3-kinase p85 subunit or grb-2. It has also been found to participate in insulin signaling.
The phosphotyrosine binding (PTB) domain of IRS-1 is 112 amino acid residues long. The PTB domain is structurally similar to the pleckstrin homology domain in which a beta-sandwich (pink and blue) is capped by an alpha-helix (purple). Also, the PTB domain has been shown to bind to acidic phospholipids eluding to a possible role in membrane localization. The protein is shown bound to its ligand, phosphotyrosine.