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.