Increased mitogenicity of an alpha beta heterodimeric PDGF receptor complex correlates with lack of RasGAP binding

The different platelet-derived growth factor (PDGF) isoforms cause activati on of their alpha and beta protein tyrosine kinase receptors through dimeri zation, Homodimerization as well as heterodimerization of receptors occur. It has been shown previously that the heterodimeric receptor complex mediat es a stronger mitogenic response than either of the homodimeric complexes. In this report, me show that in cells expressing both PDGF alpha- and beta- receptors, stimulation with PDGF-AB, which leads to preferential heterodime r formation, leads to a very low degree of phosphorylation of Tyr771 in the beta-receptor. In contrast, Tyr771 is phosphorylated in a homodimeric comp lex of beta-receptors. Phosphorylated Tyr771 is a binding site for RasGAP; an analogous site is not present in the alpha-receptor, which lacks the abi lity to associate with RasGAP, The lowered phosphorylation of Tyr771 in the heterodimeric receptor complex correlates with lowered association with Ra sGAP, as well as with a more efficient activation of Ras and MAP kinase, wh ich is consistent with the increased mitogenicity elicited by PDGF-AB, comp ared to PDGF-AA or PDGF-BB.