RGD Reference Report - 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. - Rat Genome Database

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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.

Authors: Kishi, H  Krishnamurthy, H  Galet, C  Bhaskaran, RS  Ascoli, M 
Citation: Kishi H, etal., J Biol Chem 2002 Jun 14;277(24):21939-46.
RGD ID: 724592
Pubmed: PMID:11934883   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M110894200   (Journal Full-text)

The rat follitropin receptor (rFSHR) is an unusual G protein-coupled receptor in that agonist-induced activation leads to the phosphorylation of the first and third intracellular loops instead of the C-terminal tail. To determine regions of G protein-coupled receptors 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 human follicle-stimulating hormone (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(Delta642-651), showed that both of them internalized hFSH at rates that were 2-3 times faster than rFSHR-wild type (wt). Like rFSHR-wt, however, the internalization of hFSH mediated by rFSHR-t649 and rFSHR(Delta642-651) 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 with rFSHR-wt, rFSHR(Delta642-651) displays an approximately 4-fold enhancement in binding affinity for arrestin-3 and an approximately 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 (642SATHNFHARK651) that is not phosphorylated limits internalization by lowering the affinity of the rFSHR for the endogenous non-visual arrestins.

Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cell surface  IDA 724592 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
follicle-stimulating hormone receptor activity  IDA 724592 RGD 
protein binding  IPIARR3 (Homo sapiens)724592 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Fshr  (follicle stimulating hormone receptor)

Objects referenced in this article
Gene ARR3 arrestin 3 Homo sapiens
Gene Arr3 arrestin 3 Rattus norvegicus

Additional Information