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World J Biol Chem. Dec 12, 2018; 9(3): 25-35
Published online Dec 12, 2018. doi: 10.4331/wjbc.v9.i3.25
Arrestin-mediated signaling: Is there a controversy?
Vsevolod V Gurevich, Eugenia V Gurevich
Vsevolod V Gurevich, Eugenia V Gurevich, Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, United States
Author contributions: Gurevich VV and Gurevich EV wrote the manuscript.
Supported by National Institutes of Health RO1 grants, No. EY011500; National Institutes of Health R35 grants, No. GM122491; and Cornelius Vanderbilt Endowed Chair (Vanderbilt University), No. NS065868 (to Gurevich VV) and No. DA030103 (to Gurevich EV).
Conflict-of-interest statement: The authors declare no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author to: Vsevolod V Gurevich, PhD, Professor, Department of Pharmacology, Vanderbilt University, 2200 Pierce Ave, PRB Rm 417D, Nashville, TN 37232, United States. vsevolod.gurevich@vanderbilt.edu
Telephone: +1-615-3227070 Fax: +1-615-3436532
Received: August 28, 2018
Peer-review started: August 28, 2018
First decision: September 11, 2018
Revised: October 20, 2018
Accepted: November 3, 2018
Article in press: November 3,2018
Published online: December 12, 2018
Core Tip

Core tip: Both arrestins and G proteins play important roles in G protein-coupled receptor (GPCR) signaling, including GPCR-initiated activation of mitogen-activated protein (MAP) kinases extracellular signal-regulated kinase (ERK)1/2 and c-Jun N-terminal kinase 3 (JNK3). Their roles do not overlap. G proteins participate in signal initiation, by activating MAP3Ks. Arrestins, free and GPCR-bound, function as scaffolds of the three-tiered MAP kinase cascades, facilitating signal transduction. Cells express other scaffolds, so that no MAPK cascade relies solely on arrestins. Different experimental paradigms highlight the role of G proteins or arrestins in this process, and neither can be discounted based on available evidence.