Format

Send to

Choose Destination
See comment in PubMed Commons below
Trends Pharmacol Sci. 2007 Apr;28(4):173-9. Epub 2007 Mar 9.

Phosphorylation-independent attenuation of GPCR signalling.

Author information

  • 1J. Allyn Centre for Cell Biology, Robarts Research Institute, 100 Perth Drive, PO Box 5015, London, Ontario N6A 5K8, Canada. ferguson@robarts.ca

Abstract

The uncoupling of G-protein-coupled receptors (GPCRs) from their cognate heterotrimeric G proteins provides an essential physiological 'feedback' mechanism that protects against both acute and chronic overstimulation of receptors. The primary mechanism by which GPCR activity is regulated is the feedback phosphorylation of activated GPCRs by kinases that are dependent on second messengers, GPCR kinases (GRKs) and arrestins. It has recently become apparent, however, that GRK2-mediated regulation of GPCR responsiveness also involves a phosphorylation-independent component that requires both heterotrimeric G-protein alpha-subunit interactions and GPCR binding. Moreover, in addition to GRK2, a growing number of GPCR-interacting proteins might contribute to the phosphorylation-independent G-protein uncoupling of GPCRs. Here, new information about the mechanisms underlying this phosphorylation-independent regulation of receptor and G-protein coupling is reviewed.

PMID:
17350109
DOI:
10.1016/j.tips.2007.02.008
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center