Phosphatidylinositol 3-kinase (PI 3-kinase) phosphorylates the 3' OH position of the inositol ring of inositol lipids and is composed of p85 and p110 subunits. PI 3-kinase p85 lacks PI 3-kinase activity and acts as an adapter, coupling p110 to activated protein tyrosine kinase. Two forms of p85 have been described (p85α and p85β), each possessing one SH3 and two SH2 domains. PI 3-kinase p85α, also known as GRB1, phosphatidylinositol 3-kinase regulatory 1 or p85, is a 724 amino acid protein that exists as four alternatively spliced isoforms. Involved in insulin metabolism, defects in the PI 3-kinase p85α gene have been linked to insulin resistance. PI 3-kinase p85α is polyubiquitinated in T-cells by Cbl-b, and has multiple phosphorylated amino acid residues, including a phosphorylated tyrosine residue at position 467.
