eagle-i Montana State UniversityMontana State University
See it in Search
This page is a preview of the following resource. Continue onto eagle-i search using the button on the right to see the full record.

Role of the carboxyl terminal di-leucine in phosphorylation and internalization of C5a receptor.

eagle-i ID

http://montana.eagle-i.net/i/00000130-ffef-e67b-44b9-3efb80000000

Resource Type

  1. Journal article

Properties

  1. Resource Description
    The carboxyl tail of G protein-coupled receptors contains motifs that regulate receptor interactions with intracellular partners. Activation of the human neutrophil complement fragment C5a receptor (C5aR) is terminated by phosphorylation of the carboxyl tail followed by receptor internalization. In this study, we demonstrated that bulky hydrophobic residues in the membrane-proximal region of the C5aR carboxyl tail play an important role in proper structure and function of the receptor: Substitution of leucine 319 with alanine (L319A) resulted in receptor retention in the endoplasmic reticulum, whereas a L318A substitution allowed receptor transport to the cell surface, but showed slow internalization upon activation, presumably due to a defect in phosphorylation by both PKC and GRK. Normal agonist-induced activation of ERK1/2 and intracellular calcium release suggested that the L318A mutation did not affect receptor signaling. Binding of GRK2 and PKCbetaII to intracellular loop 3 of C5aR in vitro indicated that mutagenesis of L318 did not affect kinase binding. Limited proteolysis with trypsin revealed a conformational difference between wild type and mutant receptor. Our studies support a model in which the L318/L319 stabilizes an amphipathic helix (Q305-R320) in the membrane-proximal region of C5aR.
  2. Website(s)
    http://www.ncbi.nlm.nih.gov/pubmed/18346468
  3. PubMed ID
    18346468
 
RDFRDF
 
Provenance Metadata About This Resource Record
  1. workflow state
    Published
  2. contributor
    qking (Quinton King)
  3. created
    2011-07-06T09:54:49.601-05:00
  4. creator
    qking (Quinton King)
  5. modified
    2011-07-06T23:28:32.999-05:00

Copyright © 2016 by the President and Fellows of Harvard College
The eagle-i Consortium is supported by NIH Grant #5U24RR029825-02 / Copyright 2016