Document Detail

Role of G protein-coupled receptor kinases on the agonist-induced phosphorylation and internalization of the follitropin receptor.
MedLine Citation:
PMID:  10379886     Owner:  NLM     Status:  MEDLINE    
The experiments presented herein were designed to identify members of the G protein-coupled receptor kinase (GRK) family that participate in the agonist-induced phosphorylation and internalization of the rat FSH receptor (rFSHR). Western blots of human kidney 293 cells (the cell line used in transfection experiments) and MSC-1 cells (a cell line derived from Sertoli cells that displays many of the differentiated functions of their normal counterparts) reveal the presence of GRK2 and GRK6 in both cell lines as well as GRK4 in MSC-1 cells. Cotransfection of 293 cells with the rFSHR and GRK2, GRK4alpha, or GRK6 resulted in an increase in the agonist-induced phosphorylation of the rFSHR. Cotransfections of the rFSHR with GRKs or arrestin-3 enhanced the agonist-induced internalization of the rFHSR, and combinations of GRKs and arrestin-3 were more effective than the individual components. To characterize the involvement of endogenous GRKs on phosphorylation and internalization, we inhibited endogenous GRK2 by overexpression of a kinase-deficient mutant of GRK2 or G alpha t, a scavenger of G betagamma. We also inhibited endogenous GRK6 by overexpression of a kinase-deficient mutant of GKR6. All three constructs were effective inhibitors of phosphorylation, but only the kinase-deficient mutant of GRK2 and G alpha t inhibited internalization. The inhibition of internalization induced by these two constructs was less pronounced than that induced by a dominant-negative mutant of the nonvisual arrrestins, however. The finding that inhibitors of GRK2 and GRK6 impair phosphorylation, but only the inhibitors of GRK2 impair internalization, suggests that different GRKs have differential effects on receptor internalization.
M F Lazari; X Liu; K Nakamura; J L Benovic; M Ascoli
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Molecular endocrinology (Baltimore, Md.)     Volume:  13     ISSN:  0888-8809     ISO Abbreviation:  Mol. Endocrinol.     Publication Date:  1999 Jun 
Date Detail:
Created Date:  1999-08-03     Completed Date:  1999-08-03     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8801431     Medline TA:  Mol Endocrinol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  866-78     Citation Subset:  IM    
Department of Pharmacology, The University of Iowa College of Medicine, Iowa City 52242-1109, USA.
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MeSH Terms
Arrestin / genetics,  metabolism
Cell Line / drug effects
Cyclic AMP-Dependent Protein Kinases / genetics,  metabolism*
Follicle Stimulating Hormone / metabolism*,  pharmacology
G-Protein-Coupled Receptor Kinase 4
G-Protein-Coupled Receptor Kinases
GTP Phosphohydrolases / genetics,  metabolism
Phosphorylation / drug effects
Protein-Serine-Threonine Kinases*
Receptor Protein-Tyrosine Kinases / genetics,  metabolism*
Receptors, FSH / genetics,  metabolism*
Recombinant Proteins / genetics,  metabolism
beta-Adrenergic Receptor Kinases
Grant Support
Reg. No./Substance:
0/Arrestin; 0/Receptors, FSH; 0/Recombinant Proteins; 9002-68-0/Follicle Stimulating Hormone; EC Protein-Tyrosine Kinases; EC Kinases; EC AMP-Dependent Protein Kinases; EC Receptor Kinases; EC Receptor Kinase 4; EC Receptor Kinases; EC receptor kinase 6; EC protein, human; EC protein, rat; EC 3.6.1.-/GTP Phosphohydrolases; EC

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