Differential Regulation of GPCRs-Are GRK Expression Levels the Key?

Frontiers in Cell and Developmental Biology
Edda S F MattheesJulia Drube

Abstract

G protein-coupled receptors (GPCRs) comprise the largest family of transmembrane receptors and their signal transduction is tightly regulated by GPCR kinases (GRKs) and β-arrestins. In this review, we discuss novel aspects of the regulatory GRK/β-arrestin system. Therefore, we briefly revise the origin of the "barcode" hypothesis for GPCR/β-arrestin interactions, which states that β-arrestins recognize different receptor phosphorylation states to induce specific functions. We emphasize two important parameters which may influence resulting GPCR phosphorylation patterns: (A) direct GPCR-GRK interactions and (B) tissue-specific expression and availability of GRKs and β-arrestins. In most studies that focus on the molecular mechanisms of GPCR regulation, these expression profiles are underappreciated. Hence we analyzed expression data for GRKs and β-arrestins in 61 tissues annotated in the Human Protein Atlas. We present our analysis in the context of pathophysiological dysregulation of the GPCR/GRK/β-arrestin system. This tissue-specific point of view might be the key to unraveling the individual impact of different GRK isoforms on GPCR regulation.

References

Aug 4, 1995·The Journal of Biological Chemistry·T T ChuangA De Blasi
Mar 5, 1996·Proceedings of the National Academy of Sciences of the United States of America·R WinstelM J Lohse
Nov 12, 1996·Proceedings of the National Academy of Sciences of the United States of America·M JaberB Giros
Dec 12, 1996·Biochimica Et Biophysica Acta·L A Pinna, M Ruzzene
Feb 7, 1997·The Journal of Biological Chemistry·A N Pronin, J L Benovic
Jun 30, 2001·Trends in Pharmacological Sciences·M J Marinissen, J S Gutkind
Apr 5, 2002·The Biochemical Journal·Nina E M McCarthy, Muhammad Akhtar
Jan 27, 2005·Proceedings of the National Academy of Sciences of the United States of America·Xiu-Rong RenRobert J Lefkowitz
Jan 27, 2005·Proceedings of the National Academy of Sciences of the United States of America·Jihee KimRobert J Lefkowitz
Mar 26, 2005·Protein Engineering, Design & Selection : PEDS·Veli-Pekka JaakolaAdrian Goldman
Jan 13, 2006·British Journal of Pharmacology·Graeme Milligan, Evi Kostenis
Feb 8, 2006·Pharmacology & Therapeutics·Vsevolod V Gurevich, Eugenia V Gurevich
Feb 20, 2007·Annual Review of Physiology·Scott M DeWireSudha K Shenoy
Jul 11, 2007·Proceedings of the National Academy of Sciences of the United States of America·Kunhong XiaoRobert J Lefkowitz
Nov 29, 2007·Nature Reviews. Molecular Cell Biology·William M Oldham, Heidi E Hamm
Oct 2, 2009·Current Genomics·Laurence AubryGérard Klein
May 31, 2011·Frontiers in Bioscience (Landmark Edition)·Zheng Maggie HuangWalter J Koch
Sep 10, 2011·Pharmacology & Therapeutics·Eugenia V GurevichVsevolod V Gurevich
Nov 22, 2011·The Journal of Urology·Jae Il KimYehia Daaka
Mar 24, 2012·PloS One·Arcady MushegianEugenia V Gurevich
Jun 26, 2012·British Journal of Pharmacology·Christian DollStefan Schulz
Feb 5, 2013·Cell·Rie NygaardBrian K Kobilka
Apr 17, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sandeep K RaghuwanshiRicardo M Richardson
May 23, 2013·Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia·Gurvinder KaurAndrew T Parsa
Mar 13, 2014·Annual Review of Biochemistry·Christopher J Oldfield, A Keith Dunker
Apr 1, 2014·Current Opinion in Cell Biology·Petronila PenelaFederico Mayor
Apr 1, 2014·Current Opinion in Cell Biology·Kristoff T Homan, John J G Tesmer
Apr 1, 2014·Current Opinion in Cell Biology·Dong Soo KangJeffrey L Benovic
Apr 30, 2014·Chemical Reviews·Robin van der LeeM Madan Babu
May 13, 2014·FEBS Letters·Daisuke AsaiJeong-Hun Kang
Sep 10, 2014·Current Opinion in Structural Biology·A J VenkatakrishnanM Madan Babu
Dec 23, 2014·Nature Reviews. Molecular Cell Biology·Peter E Wright, H Jane Dyson
Jan 24, 2015·Science·Mathias UhlénFredrik Pontén
Jul 7, 2015·Nature·Tilman FlockM Madan Babu
Feb 7, 2016·The Journal of Biological Chemistry·Sarah L ShammasJane Clarke
Feb 7, 2016·The Journal of Biological Chemistry·Alaji Bah, Julie D Forman-Kay

❮ Previous
Next ❯

Citations

Aug 17, 2021·Naunyn-Schmiedeberg's Archives of Pharmacology·Rasha M S M MohamedDalia M Abd El Motteleb

❮ Previous
Next ❯

Software Mentioned

R package pheatmap
Ensembl
R package
R
pheatmap R

Related Concepts

Related Feeds

Cell Signaling by Tyrosine Kinases

Receptor tyrosine kinases (RTKs) are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. RTKs have been shown not only to be key regulators of normal cellular processes but also to have a critical role in the development and progression of many types of cancer. Discover the latest research on cell signaling and RTK here.