Molecular basis of the regulation of the lutropin/choriogonadotropin receptor.
The studies summarized here clearly show that the phosphorylation of one or more serine residues (S635, S639, S649 and/or S652) present in the C-terminal tail of the LHR is necessary, but not sufficient, for the agonist-induced uncoupling of the LHR from adenylate cyclase and for the endocytosis of the agonist-receptor complex. Simultaneous mutation of these four serines to alanines decreases the rate of agonist-induced uncoupling and the rate of agonist-induced internalization. This mutation does not affect the magnitude of agonist-induced uncoupling attained upon a long incubation with agonist, nor does it reduce the rate of internalization of the agonist-bound LHR to that of the free LHR. Thus additional molecular interactions and/or post-translational modifications of the LHR are needed for uncoupling and down-regulation.
Ascoli
M
M
Department of Pharmacology, University of Iowa, College of Medicine, Iowa City 52242, USA.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007984:Leydig Cell Tumor / Q000503:physiopathology; D007985:Leydig Cells / Q000502:physiology; D008297:Male; D008958:Models, Molecular; D011487:Protein Conformation; D011974:Receptors, LH / Q000096:biosynthesis / Q000737:chemistry* / Q000502:physiology*; D012694:Serine
D006063:Chorionic Gonadotropin; D011974:Receptors, LH; D012694:Serine; D000262:Adenylyl Cyclases