4.5 Review Book Chapter

Physiological roles of G protein-coupled receptor kinases and arrestins

Journal

ANNUAL REVIEW OF PHYSIOLOGY
Volume 69, Issue -, Pages 511-534

Publisher

ANNUAL REVIEWS
DOI: 10.1146/annurev.physiol.69.022405.154731

Keywords

GPCR; GRK; brain; heart; lung; immunity

Categories

Funding

  1. NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM059989] Funding Source: NIH RePORTER
  2. NATIONAL INSTITUTE ON DRUG ABUSE [R01DA016347] Funding Source: NIH RePORTER
  3. NIDA NIH HHS [DA016347] Funding Source: Medline
  4. NIGMS NIH HHS [GM59989] Funding Source: Medline

Ask authors/readers for more resources

Heterotrimeric G protein-coupled receptors (GPCRs) are found on the surface of all cells of inulticellular organisms and are major mediators of intercellular communication. More than 800 distinct GPCRs are present in the human genome, and individual receptor subtypes respond to hormones, neurotransmitters, chemokines, odorants, or tastants. GPCRs represent the most widely targeted pharmacological protein class. Because drugs that target GPCRs often engage receptor regulatory mechanisms that limit drug effectiveness, particularly in chronic treatment, there is great interest in understanding how GPCRs are regulated, as a basis for designing therapeutic drugs that evade this regulation. The major GPCR regulatory pathway involves phosphorylation of activated receptors by G protein-coupled receptor kinases (GRKs), followed by binding of arrestin proteins, which prevent receptors from activating downstream heterotrimeric G protein pathways while allowing activation of arrestin-dependent signaling pathways. Although the general mechanisms of GRK-arrestin regulation have been well explored in model cell systems and with purified proteins, much less is known about the role of GRK-arrestin regulation of receptors in physiological and pathophysiological settings. This review focuses oil the physiological functions and potential pathophysiological roles of GRKs and arrestins in human disorders as well as on recent studies using knockout and transgenic mice to explore the role of GRK-arrestin regulation of GPCRs in vivo.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.5
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available