Cross-talk between receptors with intrinsic tyrosine kinase activity and alpha(1b)-adrenoceptors

The effect of epidermal growth factor (EGF) and platelet-derived growth fac tor (PDGF) on the phosphorylation and function of alpha(1b)-adrenoceptors t ransfected into Rat-1 fibroblasts was studied. EGF and PDGF increased the p hosphorylation of these adrenoceptors. The effect of EGF was blocked by tyr phostin AG1478 and that of PDGF was blocked by tyrphostin AC1296, inhibitor s of the intrinsic tyrosine kinase activities of the receptors for these gr owth factors. Wortmannin, an inhibitor of phosphoinositide 3-kinase, blocke d the alpha(1b)-adrenoceptor phosphorylation induced by EGF but not that in duced by PDGF. Inhibition of protein kinase C blocked the adrenoceptor phos phorylation induced by EGF and PDGF. The ability of noradrenaline to increa se [S-35]guanosine 5'-[gamma-thio]triphosphate ([S-35]GTP[S]) binding in me mbrane preparations was used as an index of the functional coupling of the alpha(1b)-adrenoceptors and G-proteins. Noradrenaline-stimulated [S-35]GTP[ S] binding was markedly decreased in membranes from cells pretreated with E GF or PDGF. Our data indicate that: (i) activation of EGF and PDGF receptor s induces phosphorylation of alpha(1b)-adrenoceptors, (ii) phosphatidylinos itol 3-kinase is involved in the EGF response, but does not seem to play a major role in the action of PDGF, (iii) protein kinase C mediates this acti on of both growth factors and (iv) the phosphorylation of alpha(1b)-adrenoc eptors induced by EGF and PDGF is associated with adrenoceptor desensitizat ion.