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Atypical p38 Signaling, Activation, and Implications for Disease
The mitogen-activated protein kinase (MAPK) p38 is an essential family of kinases, regulating responses to environmental stress and inflammation. There is an ever-increasing plethora of physiological and pathophysiological conditions attributed to p38 activity, ranging from cell division and embryon...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073329/ https://www.ncbi.nlm.nih.gov/pubmed/33920735 http://dx.doi.org/10.3390/ijms22084183 |
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author | Burton, Jeremy C. Antoniades, William Okalova, Jennifer Roos, Morgan M. Grimsey, Neil J. |
author_facet | Burton, Jeremy C. Antoniades, William Okalova, Jennifer Roos, Morgan M. Grimsey, Neil J. |
author_sort | Burton, Jeremy C. |
collection | PubMed |
description | The mitogen-activated protein kinase (MAPK) p38 is an essential family of kinases, regulating responses to environmental stress and inflammation. There is an ever-increasing plethora of physiological and pathophysiological conditions attributed to p38 activity, ranging from cell division and embryonic development to the control of a multitude of diseases including retinal, cardiovascular, and neurodegenerative diseases, diabetes, and cancer. Despite the decades of intense investigation, a viable therapeutic approach to disrupt p38 signaling remains elusive. A growing body of evidence supports the pathological significance of an understudied atypical p38 signaling pathway. Atypical p38 signaling is driven by a direct interaction between the adaptor protein TAB1 and p38α, driving p38 autophosphorylation independent from the classical MKK3 and MKK6 pathways. Unlike the classical MKK3/6 signaling pathway, atypical signaling is selective for just p38α, and at present has only been characterized during pathophysiological stimulation. Recent studies have linked atypical signaling to dermal and vascular inflammation, myocardial ischemia, cancer metastasis, diabetes, complications during pregnancy, and bacterial and viral infections. Additional studies are required to fully understand how, when, where, and why atypical p38 signaling is induced. Furthermore, the development of selective TAB1-p38 inhibitors represents an exciting new opportunity to selectively inhibit pathological p38 signaling in a wide array of diseases. |
format | Online Article Text |
id | pubmed-8073329 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-80733292021-04-27 Atypical p38 Signaling, Activation, and Implications for Disease Burton, Jeremy C. Antoniades, William Okalova, Jennifer Roos, Morgan M. Grimsey, Neil J. Int J Mol Sci Review The mitogen-activated protein kinase (MAPK) p38 is an essential family of kinases, regulating responses to environmental stress and inflammation. There is an ever-increasing plethora of physiological and pathophysiological conditions attributed to p38 activity, ranging from cell division and embryonic development to the control of a multitude of diseases including retinal, cardiovascular, and neurodegenerative diseases, diabetes, and cancer. Despite the decades of intense investigation, a viable therapeutic approach to disrupt p38 signaling remains elusive. A growing body of evidence supports the pathological significance of an understudied atypical p38 signaling pathway. Atypical p38 signaling is driven by a direct interaction between the adaptor protein TAB1 and p38α, driving p38 autophosphorylation independent from the classical MKK3 and MKK6 pathways. Unlike the classical MKK3/6 signaling pathway, atypical signaling is selective for just p38α, and at present has only been characterized during pathophysiological stimulation. Recent studies have linked atypical signaling to dermal and vascular inflammation, myocardial ischemia, cancer metastasis, diabetes, complications during pregnancy, and bacterial and viral infections. Additional studies are required to fully understand how, when, where, and why atypical p38 signaling is induced. Furthermore, the development of selective TAB1-p38 inhibitors represents an exciting new opportunity to selectively inhibit pathological p38 signaling in a wide array of diseases. MDPI 2021-04-17 /pmc/articles/PMC8073329/ /pubmed/33920735 http://dx.doi.org/10.3390/ijms22084183 Text en © 2021 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 Burton, Jeremy C. Antoniades, William Okalova, Jennifer Roos, Morgan M. Grimsey, Neil J. Atypical p38 Signaling, Activation, and Implications for Disease |
title | Atypical p38 Signaling, Activation, and Implications for Disease |
title_full | Atypical p38 Signaling, Activation, and Implications for Disease |
title_fullStr | Atypical p38 Signaling, Activation, and Implications for Disease |
title_full_unstemmed | Atypical p38 Signaling, Activation, and Implications for Disease |
title_short | Atypical p38 Signaling, Activation, and Implications for Disease |
title_sort | atypical p38 signaling, activation, and implications for disease |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073329/ https://www.ncbi.nlm.nih.gov/pubmed/33920735 http://dx.doi.org/10.3390/ijms22084183 |
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