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Scaffolding of Mitogen-Activated Protein Kinase Signaling by β-Arrestins

β-arrestins were initially identified to desensitize and internalize G-protein-coupled receptors (GPCRs). Receptor-bound β-arrestins also initiate a second wave of signaling by scaffolding mitogen-activated protein kinase (MAPK) signaling components, MAPK kinase kinase, MAPK kinase, and MAPK. In par...

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Detalles Bibliográficos
Autores principales: Kim, Kiae, Han, Yeonjin, Duan, Longhan, Chung, Ka Young
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8778048/
https://www.ncbi.nlm.nih.gov/pubmed/35055186
http://dx.doi.org/10.3390/ijms23021000
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author Kim, Kiae
Han, Yeonjin
Duan, Longhan
Chung, Ka Young
author_facet Kim, Kiae
Han, Yeonjin
Duan, Longhan
Chung, Ka Young
author_sort Kim, Kiae
collection PubMed
description β-arrestins were initially identified to desensitize and internalize G-protein-coupled receptors (GPCRs). Receptor-bound β-arrestins also initiate a second wave of signaling by scaffolding mitogen-activated protein kinase (MAPK) signaling components, MAPK kinase kinase, MAPK kinase, and MAPK. In particular, β-arrestins facilitate ERK1/2 or JNK3 activation by scaffolding signal cascade components such as ERK1/2-MEK1-cRaf or JNK3-MKK4/7-ASK1. Understanding the precise molecular and structural mechanisms of β-arrestin-mediated MAPK scaffolding assembly would deepen our understanding of GPCR-mediated MAPK activation and provide clues for the selective regulation of the MAPK signaling cascade for therapeutic purposes. Over the last decade, numerous research groups have attempted to understand the molecular and structural mechanisms of β-arrestin-mediated MAPK scaffolding assembly. Although not providing the complete mechanism, these efforts suggest potential binding interfaces between β-arrestins and MAPK signaling components and the mechanism for MAPK signal amplification by β-arrestin-mediated scaffolding. This review summarizes recent developments of cellular and molecular works on the scaffolding mechanism of β-arrestin for MAPK signaling cascade.
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spelling pubmed-87780482022-01-22 Scaffolding of Mitogen-Activated Protein Kinase Signaling by β-Arrestins Kim, Kiae Han, Yeonjin Duan, Longhan Chung, Ka Young Int J Mol Sci Review β-arrestins were initially identified to desensitize and internalize G-protein-coupled receptors (GPCRs). Receptor-bound β-arrestins also initiate a second wave of signaling by scaffolding mitogen-activated protein kinase (MAPK) signaling components, MAPK kinase kinase, MAPK kinase, and MAPK. In particular, β-arrestins facilitate ERK1/2 or JNK3 activation by scaffolding signal cascade components such as ERK1/2-MEK1-cRaf or JNK3-MKK4/7-ASK1. Understanding the precise molecular and structural mechanisms of β-arrestin-mediated MAPK scaffolding assembly would deepen our understanding of GPCR-mediated MAPK activation and provide clues for the selective regulation of the MAPK signaling cascade for therapeutic purposes. Over the last decade, numerous research groups have attempted to understand the molecular and structural mechanisms of β-arrestin-mediated MAPK scaffolding assembly. Although not providing the complete mechanism, these efforts suggest potential binding interfaces between β-arrestins and MAPK signaling components and the mechanism for MAPK signal amplification by β-arrestin-mediated scaffolding. This review summarizes recent developments of cellular and molecular works on the scaffolding mechanism of β-arrestin for MAPK signaling cascade. MDPI 2022-01-17 /pmc/articles/PMC8778048/ /pubmed/35055186 http://dx.doi.org/10.3390/ijms23021000 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Kim, Kiae
Han, Yeonjin
Duan, Longhan
Chung, Ka Young
Scaffolding of Mitogen-Activated Protein Kinase Signaling by β-Arrestins
title Scaffolding of Mitogen-Activated Protein Kinase Signaling by β-Arrestins
title_full Scaffolding of Mitogen-Activated Protein Kinase Signaling by β-Arrestins
title_fullStr Scaffolding of Mitogen-Activated Protein Kinase Signaling by β-Arrestins
title_full_unstemmed Scaffolding of Mitogen-Activated Protein Kinase Signaling by β-Arrestins
title_short Scaffolding of Mitogen-Activated Protein Kinase Signaling by β-Arrestins
title_sort scaffolding of mitogen-activated protein kinase signaling by β-arrestins
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8778048/
https://www.ncbi.nlm.nih.gov/pubmed/35055186
http://dx.doi.org/10.3390/ijms23021000
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