Cargando…

Arrestin-mediated signaling: Is there a controversy?

The activation of the mitogen-activated protein (MAP) kinases extracellular signal-regulated kinase (ERK)1/2 was traditionally used as a readout of signaling of G protein-coupled receptors (GPCRs) via arrestins, as opposed to conventional GPCR signaling via G proteins. Several recent studies using H...

Descripción completa

Detalles Bibliográficos
Autores principales: Gurevich, Vsevolod V, Gurevich, Eugenia V
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Baishideng Publishing Group Inc 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6305498/
https://www.ncbi.nlm.nih.gov/pubmed/30595812
http://dx.doi.org/10.4331/wjbc.v9.i3.25
_version_ 1783382578995134464
author Gurevich, Vsevolod V
Gurevich, Eugenia V
author_facet Gurevich, Vsevolod V
Gurevich, Eugenia V
author_sort Gurevich, Vsevolod V
collection PubMed
description The activation of the mitogen-activated protein (MAP) kinases extracellular signal-regulated kinase (ERK)1/2 was traditionally used as a readout of signaling of G protein-coupled receptors (GPCRs) via arrestins, as opposed to conventional GPCR signaling via G proteins. Several recent studies using HEK293 cells where all G proteins were genetically ablated or inactivated, or both non-visual arrestins were knocked out, demonstrated that ERK1/2 phosphorylation requires G protein activity, but does not necessarily require the presence of non-visual arrestins. This appears to contradict the prevailing paradigm. Here we discuss these results along with the recent data on gene edited cells and arrestin-mediated signaling. We suggest that there is no real controversy. G proteins might be involved in the activation of the upstream-most MAP3Ks, although in vivo most MAP3K activation is independent of heterotrimeric G proteins, being initiated by receptor tyrosine kinases and/or integrins. As far as MAP kinases are concerned, the best-established role of arrestins is scaffolding of the three-tiered cascades (MAP3K-MAP2K-MAPK). Thus, it seems likely that arrestins, GPCR-bound and free, facilitate the propagation of signals in these cascades, whereas signal initiation via MAP3K activation may be independent of arrestins. Different MAP3Ks are activated by various inputs, some of which are mediated by G proteins, particularly in cell culture, where we artificially prevent signaling by receptor tyrosine kinases and integrins, thereby favoring GPCR-induced signaling. Thus, there is no reason to change the paradigm: Arrestins and G proteins play distinct non-overlapping roles in cell signaling.
format Online
Article
Text
id pubmed-6305498
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Baishideng Publishing Group Inc
record_format MEDLINE/PubMed
spelling pubmed-63054982018-12-28 Arrestin-mediated signaling: Is there a controversy? Gurevich, Vsevolod V Gurevich, Eugenia V World J Biol Chem Minireviews The activation of the mitogen-activated protein (MAP) kinases extracellular signal-regulated kinase (ERK)1/2 was traditionally used as a readout of signaling of G protein-coupled receptors (GPCRs) via arrestins, as opposed to conventional GPCR signaling via G proteins. Several recent studies using HEK293 cells where all G proteins were genetically ablated or inactivated, or both non-visual arrestins were knocked out, demonstrated that ERK1/2 phosphorylation requires G protein activity, but does not necessarily require the presence of non-visual arrestins. This appears to contradict the prevailing paradigm. Here we discuss these results along with the recent data on gene edited cells and arrestin-mediated signaling. We suggest that there is no real controversy. G proteins might be involved in the activation of the upstream-most MAP3Ks, although in vivo most MAP3K activation is independent of heterotrimeric G proteins, being initiated by receptor tyrosine kinases and/or integrins. As far as MAP kinases are concerned, the best-established role of arrestins is scaffolding of the three-tiered cascades (MAP3K-MAP2K-MAPK). Thus, it seems likely that arrestins, GPCR-bound and free, facilitate the propagation of signals in these cascades, whereas signal initiation via MAP3K activation may be independent of arrestins. Different MAP3Ks are activated by various inputs, some of which are mediated by G proteins, particularly in cell culture, where we artificially prevent signaling by receptor tyrosine kinases and integrins, thereby favoring GPCR-induced signaling. Thus, there is no reason to change the paradigm: Arrestins and G proteins play distinct non-overlapping roles in cell signaling. Baishideng Publishing Group Inc 2018-12-12 2018-12-12 /pmc/articles/PMC6305498/ /pubmed/30595812 http://dx.doi.org/10.4331/wjbc.v9.i3.25 Text en ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved. http://creativecommons.org/licenses/by-nc/4.0/ 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.
spellingShingle Minireviews
Gurevich, Vsevolod V
Gurevich, Eugenia V
Arrestin-mediated signaling: Is there a controversy?
title Arrestin-mediated signaling: Is there a controversy?
title_full Arrestin-mediated signaling: Is there a controversy?
title_fullStr Arrestin-mediated signaling: Is there a controversy?
title_full_unstemmed Arrestin-mediated signaling: Is there a controversy?
title_short Arrestin-mediated signaling: Is there a controversy?
title_sort arrestin-mediated signaling: is there a controversy?
topic Minireviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6305498/
https://www.ncbi.nlm.nih.gov/pubmed/30595812
http://dx.doi.org/10.4331/wjbc.v9.i3.25
work_keys_str_mv AT gurevichvsevolodv arrestinmediatedsignalingisthereacontroversy
AT gurevicheugeniav arrestinmediatedsignalingisthereacontroversy