Phosphorylation of the lutropin/choriogonadotropin receptor facilitates uncoupling of the receptor from adenylyl cyclase and endocytosis of the bound hormone

被引:45
作者
Wang, Z [1 ]
Liu, XB [1 ]
Ascoli, M [1 ]
机构
[1] UNIV IOWA, DEPT PHARMACOL, IOWA CITY, IA 52242 USA
关键词
D O I
10.1210/me.11.2.183
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Stably transfected cell lines expressing the wildtype rat LH/CG receptor (rLHR) or a full-length rLHR in which S-635, T-638, S-639, S-649, and S-653 were simultaneously mutated to alanine residues (designated rLHR-5S/T-->A) were used to probe the importance of receptor phosphorylation on the regulation of receptor functions. The mutant receptor binds hCG with high affinity and transduces the hormonal signal into increases in cAMP and inositol phosphate accumulation comparable in magnitude to those elicited by the wild-type receptor. In contrast to cells expressing rLHR-wt, which respond to hCG or phorbol 12-myristate 13-acetate stimulation with an increase in rLHR phosphorylation, the phosphorylation of rLHR in cells expressing rLHR-5S/T-->A is severely blunted. Likewise, the phorbol 12-myristate 13-acetate-induced desensitization of hCG-induced cAMP accumulation is drastically reduced in cells expressing rLHR-5S/T-->A. In contrast, the hCG-induced desensitization of hCG-induced cAMP accumulation is delayed, but not abolished, in cells expressing rLHR-5S/T-->A. Lastly, the rate of internalization of the receptor-bound hCG is slower in cells expressing rLHR-5S/T-->A than in cells expressing rLHR-wt. These results show that phosphorylation of rLHR is necessary, but not sufficient, for uncoupling of the receptor from adenylyl cyclase and for endocytosis of the receptor-bound hormone.
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页码:183 / 192
页数:10
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