Abstract
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.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / analogs & derivatives
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1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / pharmacology
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Adenosine Diphosphate Ribose / metabolism
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Adenylate Cyclase Toxin
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Adenylyl Cyclases / metabolism
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Animals
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Cell-Free System
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Chorionic Gonadotropin / pharmacology
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Enzyme Inhibitors / pharmacology
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Epidermal Growth Factor / pharmacology
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ErbB Receptors / metabolism*
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Female
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GTP-Binding Protein alpha Subunits, Gi-Go / metabolism
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Genistein / pharmacology
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Membrane Proteins / drug effects
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Membrane Proteins / metabolism
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Ovary / drug effects
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Ovary / enzymology
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Ovary / metabolism
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Pertussis Toxin
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Phosphorylation
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Protein Kinase Inhibitors
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Protein-Tyrosine Kinases / antagonists & inhibitors
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Rats
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Receptors, LH / metabolism*
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Time Factors
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Tyrosine / metabolism*
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Virulence Factors, Bordetella / pharmacology
Substances
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Adenylate Cyclase Toxin
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Chorionic Gonadotropin
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Enzyme Inhibitors
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Membrane Proteins
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Protein Kinase Inhibitors
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Receptors, LH
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Virulence Factors, Bordetella
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Adenosine Diphosphate Ribose
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Tyrosine
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Epidermal Growth Factor
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1-(5-isoquinolinylsulfonyl)-3-methylpiperazine
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1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
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Genistein
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Pertussis Toxin
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ErbB Receptors
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Protein-Tyrosine Kinases
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GTP-Binding Protein alpha Subunits, Gi-Go
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Adenylyl Cyclases