Association of phosphatidylinositol 3-kinase with the insulin receptor: compartmentation in rat liver

Phosphatidylinositol 3-kinase (PI 3-kinase) plays an important role in a va riety of hormone and growth factor-mediated intracellular signaling cascade s and has been implicated in the regulation of a number of metabolic effect s of insulin, including glucose transport and glycogen synthase activation. In the present study we have examined 1) the association of PI 3-kinase wi th the insulin receptor kinase (IRK) in rat liver and 2) the subcellular di stribution of PI 3-kinase- IRK interaction. Insulin treatment promoted a ra pid and pronounced recruitment of PI 3-kinase to IRKs located at the plasma membrane, whereas no increase in association with endosomal IRKs was obser ved. In contrast to IRS-1-associated PI 3-kinase activity, association of P I 3-kinase with the plasma membrane IRK did not augment the specific activi ty of the lipid kinase. With use of the selective PI 3-kinase inhibitor wor tmannin, our data suggest that the cell surface IRK beta-subunit is not a s ubstrate for the serine kinase activity of PI 3-kinase. The functional sign ificance for the insulin-stimulated selective recruitment of PI 3-kinase to cell surface IRKs remains to be elucidated.