Epidermal growth factor-induced heterologous desensitization of the luteinizing hormone/choriogonadotropin receptor in a cell-free membrane preparation is associated with the tyrosine phosphorylation of the epidermal growth factor receptor.
Epidermal growth factor (EGF) attenuated hCG-stimulated adenylyl cyclase activity in rat luteal and follicular membranes. H7, an equipotent serine/threonine protein kinase inhibitor of cAMP-dependent protein kinases, cGMP-dependent protein kinases, and lipid-dependent protein kinase C, did not effect the ability of EGF to decrease hCG-responsive adenylyl cyclase activity, suggesting that a serine/threonine phosphorylation event catalyzed by these kinases was not critically involved in EGF-induced desensitization. Likewise, pertussis toxin-catalyzed ADP-ribosylation of a 40-kDa luteal membrane protein, which exhibited immunoreactivity with an antibody against Gi alpha, did not hinder the ability of EGF to attenuate hCG-stimulated adenylyl cyclase activity, indicating that Gi did not mediate EGF-induced desensitization. Rather, EGF-induced heterologous desensitization of LH/CG receptor in ovarian membranes was closely associated with the specific and prominent tyrosine phosphorylation of the 170-kDa EGF receptor. Both EGF-stimulated autophosphorylation of EGF receptor and EGF-induced LH/CG receptor desensitization were attenuated by genistein, a tyrosine kinase inhibitor. These results suggest that tyrosine phosphorylation of the 170-kDa EGF receptor is a necessary component of the signaling pathway in EGF-induced heterologous desensitization of the LH/CG receptor.
Lamm
M L
ML
Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Rajagopalan-Gupta
R M
RM
Hunzicker-Dunn
M
M
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002474:Cell-Free System; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D019833:Genistein / Q000494:pharmacology; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism; D010053:Ovary / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D037342:Pertussis Toxin; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D051381:Rats; D011974:Receptors, LH / Q000378:metabolism*; D013997:Time Factors; D014443:Tyrosine / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D006063:Chorionic Gonadotropin; D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D047428:Protein Kinase Inhibitors; D011974:Receptors, LH; D010566:Virulence Factors, Bordetella; D000246:Adenosine Diphosphate Ribose; D014443:Tyrosine; D004815:Epidermal Growth Factor; C080501:1-(5-isoquinolinylsulfonyl)-3-methylpiperazine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D019833:Genistein; D037342:Pertussis Toxin; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D000262:Adenylyl Cyclases