The PI 3-kinase isoforms p110 alpha and p110 beta have differential roles in PDGF- and insulin-mediated signaling

Phosphoinositide 3'-kinases constitute a family of lipid kinases implicated in signal transduction through tyrosine kinase receptors and heterotrimeri c G protein-linked receptors, Phosphoinositide 3'-kinases that bind to the platelet-derived growth factor receptor are composed of two subunits: the p 85 subunit acts as an adapter and couples the catalytic p110 subunit to the activated receptor, There are different isoforms of p85 as well as of p110 , the individual roles of which have been elusive. Using microinjection of inhibitory antibodies specific for either p110 alpha or p110 beta we have i nvestigated the involvement of the two p110 isoforms in platelet-derived gr owth factor- and insulin-induced actin reorganization in porcine aortic end othelial cells. We have found that antibodies against p110 alpha, but not a ntibodies against p110 beta, inhibit platelet-derived growth factor-stimula ted actin reorganization, whereas the reverse is true for inhibition of ins ulin-induced actin reorganization. These data indicate that the two phospho inositide 3'-kinase isoforms have distinct roles in signal transduction pat hways induced by platelet-derived growth factor and insulin.