Cross-talk between receptors with intrinsic tyrosine kinase activity and alpha1b-adrenoceptors.
The effect of epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) on the phosphorylation and function of alpha(1b)-adrenoceptors transfected into Rat-1 fibroblasts was studied. EGF and PDGF increased the phosphorylation of these adrenoceptors. The effect of EGF was blocked by tyrphostin AG1478 and that of PDGF was blocked by tyrphostin AG1296, inhibitors of the intrinsic tyrosine kinase activities of the receptors for these growth factors. Wortmannin, an inhibitor of phosphoinositide 3-kinase, blocked the alpha(1b)-adrenoceptor phosphorylation induced by EGF but not that induced by PDGF. Inhibition of protein kinase C blocked the adrenoceptor phosphorylation induced by EGF and PDGF. The ability of noradrenaline to increase [(35)S]guanosine 5'-[gamma-thio]triphosphate ([(35)S]GTP[S]) binding in membrane preparations was used as an index of the functional coupling of the alpha(1b)-adrenoceptors and G-proteins. Noradrenaline-stimulated [(35)S]GTP[S] binding was markedly decreased in membranes from cells pretreated with EGF or PDGF. Our data indicate that: (i) activation of EGF and PDGF receptors induces phosphorylation of alpha(1b)-adrenoceptors, (ii) phosphatidylinositol 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 action of both growth factors and (iv) the phosphorylation of alpha(1b)-adrenoceptors induced by EGF and PDGF is associated with adrenoceptor desensitization.
del Carmen Medina
L
L
Departamento de Biología Celular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Apartado Postal 70-248, México, D.F. 04510.
Vázquez-Prado
J
J
García-Sáinz
J A
JA
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011799:Quinazolines; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D019311:Staurosporine / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection; D020032:Tyrphostins / Q000494:pharmacology; D000077191:Wortmannin
D000316:Adrenergic alpha-Agonists; D000730:Androstadienes; D004791:Enzyme Inhibitors; D007211:Indoles; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010982:Platelet-Derived Growth Factor; D011799:Quinazolines; D018340:Receptors, Adrenergic, alpha-1; D020032:Tyrphostins; C106250:6,7-dimethoxy-3-phenylquinoxaline; C101044:RTKI cpd; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D004815:Epidermal Growth Factor; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D011493:Protein Kinase C; D019311:Staurosporine; C064758:Ro 31-8220; D009638:Norepinephrine; D000077191:Wortmannin