| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Papers In Press, published online ahead of print April 4, 2002
Pharmacology, The University of Iowa, Iowa city, Iowa 52242-1109
Corresponding Author: mario-ascoli{at}uiowa.edu
The rat follitropin receptor (rFSHR) is an unusual G protein-coupled receptor (GPCR) in that agonist-induced activation leads to the phosphorylation of the first and third intracellular loops, instead of the C-terminal tail. In order to determine regions of GPCRs that affect internalization independently of phosphorylation we examined the effects of truncations of the C-terminal tail of the rFSHR on agonist-induced internalization. Our studies show that progressive truncations of a region flanked by residues 642 and 651 enhance the internalization of hFSH. Further characterization of a mutant truncated at residue 649 (designated rFSHR-t649) and another mutant in which the 642-651 region was deleted in the context of the full length rFSHR, designated rFSHR(D642-651), showed that both of them internalized hFSH at rates that were 2-3 times faster than rFSHR-wt. Like rFSHR-wt, however, the internalization of hFSH mediated by rFSHR-t649 and rFSHR(D642-651) can be inhibited with dominant-negative mutants of the non-visual arrestins or dynamin. Alanine scanning mutagenesis of the 642-651 region suggests that the effects on internalization are not mediated by a single residue, however. In an attempt to understand the molecular basis of the enhanced internalization of hFSH mediated by these mutants we used an assay that can be readily used to assess the association of the rFSHR with the arrestin-3 in co-transfected cells. Using this assay we were able to show that, when compared to rFSHR-wt, rFSHR(D642-651) displays a ~4-fold enhancement in binding affinity for arrestin-3 and a ~1.7-fold reduction in maximal arrestin-3 binding capacity. We conclude that a short linear sequence present in the C-terminal tail of the rFSHR (S642ATHNFHARK651) that is not phosphorylated limits internalization by lowering the affinity of the rFSHR for the endogenous non-visual arrestins.
J. Biol. Chem, 10.1074/jbc.M110894200
Submitted on November 13, 2001
Revised on March 20, 2002
Accepted on April 3, 2002
Identification of a short linear sequence present in the C-terminal tail of the rat follitropin receptor that modulates arrestin-3 binding in a phosphorylation-independent fashion
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  L. Stanasila, L. Abuin, J. Dey, and S. Cotecchia Different Internalization Properties of the {alpha}1a- and {alpha}1b-Adrenergic Receptor Subtypes: The Potential Role of Receptor Interaction with {beta}-Arrestins and AP50 Mol. Pharmacol., September 1, 2008; 74(3): 562 - 573. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Uribe, T. Zarinan, M. A. Perez-Solis, R. Gutierrez-Sagal, E. Jardon-Valadez, A. Pineiro, J. A. Dias, and A. Ulloa-Aguirre Functional and Structural Roles of Conserved Cysteine Residues in the Carboxyl-Terminal Domain of the Follicle-Stimulating Hormone Receptor in Human Embryonic Kidney 293 Cells Biol Reprod, May 1, 2008; 78(5): 869 - 882. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Peverelli, G. Mantovani, D. Calebiro, A. Doni, S. Bondioni, A. Lania, P. Beck-Peccoz, and A. Spada The Third Intracellular Loop of the Human Somatostatin Receptor 5 Is Crucial for Arrestin Binding and Receptor Internalization after Somatostatin Stimulation Mol. Endocrinol., March 1, 2008; 22(3): 676 - 688. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Kara, P. Crepieux, C. Gauthier, N. Martinat, V. Piketty, F. Guillou, and E. Reiter A Phosphorylation Cluster of Five Serine and Threonine Residues in the C-Terminus of the Follicle-Stimulating Hormone Receptor Is Important for Desensitization But Not for ss-Arrestin-Mediated ERK Activation Mol. Endocrinol., November 1, 2006; 20(11): 3014 - 3026. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Marion, E. Kara, P. Crepieux, V. Piketty, N. Martinat, F. Guillou, and E. Reiter G protein-coupled receptor kinase 2 and {beta}-arrestins are recruited to FSH receptor in stimulated rat primary Sertoli cells. J. Endocrinol., August 1, 2006; 190(2): 341 - 350. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O.-J. Kim, B. R. Gardner, D. B. Williams, P. S. Marinec, D. M. Cabrera, J. D. Peters, C. C. Mak, K.-M. Kim, and D. R. Sibley The Role of Phosphorylation in D1 Dopamine Receptor Desensitization: EVIDENCE FOR A NOVEL MECHANISM OF ARRESTIN ASSOCIATION J. Biol. Chem., February 27, 2004; 279(9): 7999 - 8010. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Galet, T. Hirakawa, and M. Ascoli The Postendocytotic Trafficking of the Human Lutropin Receptor Is Mediated by a Transferable Motif Consisting of the C-Terminal Cysteine and an Upstream Leucine Mol. Endocrinol., February 1, 2004; 18(2): 434 - 446. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Vishnivetskiy, M. M. Hosey, J. L. Benovic, and V. V. Gurevich Mapping the Arrestin-Receptor Interface: STRUCTURAL ELEMENTS RESPONSIBLE FOR RECEPTOR SPECIFICITY OF ARRESTIN PROTEINS J. Biol. Chem., January 9, 2004; 279(2): 1262 - 1268. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Hirakawa, C. Galet, M. Kishi, and M. Ascoli GIPC Binds to the Human Lutropin Receptor (hLHR) through an Unusual PDZ Domain Binding Motif, and It Regulates the Sorting of the Internalized Human Choriogonadotropin and the Density of Cell Surface hLHR J. Biol. Chem., December 5, 2003; 278(49): 49348 - 49357. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
