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p38γ MAPK Inflammatory and Metabolic Signaling in Physiology and Disease

p38γ MAPK (also called ERK6 or SAPK3) is a family member of stress-activated MAPKs and has common and specific roles as compared to other p38 proteins in signal transduction. Recent studies showed that, in addition to inflammation, p38γ metabolic signaling is involved in physiological exercise and i...

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Autores principales: Qi, Xiao-Mei, Chen, Guan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10341180/
https://www.ncbi.nlm.nih.gov/pubmed/37443708
http://dx.doi.org/10.3390/cells12131674
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author Qi, Xiao-Mei
Chen, Guan
author_facet Qi, Xiao-Mei
Chen, Guan
author_sort Qi, Xiao-Mei
collection PubMed
description p38γ MAPK (also called ERK6 or SAPK3) is a family member of stress-activated MAPKs and has common and specific roles as compared to other p38 proteins in signal transduction. Recent studies showed that, in addition to inflammation, p38γ metabolic signaling is involved in physiological exercise and in pathogenesis of cancer, diabetes, and Alzheimer’s disease, indicating its potential as a therapeutic target. p38γphosphorylates at least 19 substrates through which p38γ activity is further modified to regulate life-important cellular processes such as proliferation, differentiation, cell death, and transformation, thereby impacting biological outcomes of p38γ-driven pathogenesis. P38γ signaling is characterized by its unique reciprocal regulation with its specific phosphatase PTPH1 and by its direct binding to promoter DNAs, leading to transcriptional activation of targets including cancer-like stem cell drivers. This paper will review recent findings about p38γ inflammation and metabolic signaling in physiology and diseases. Moreover, we will discuss the progress in the development of p38γ-specific pharmacological inhibitors for therapeutic intervention in disease prevention and treatment by targeting the p38γ signaling network.
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spelling pubmed-103411802023-07-14 p38γ MAPK Inflammatory and Metabolic Signaling in Physiology and Disease Qi, Xiao-Mei Chen, Guan Cells Review p38γ MAPK (also called ERK6 or SAPK3) is a family member of stress-activated MAPKs and has common and specific roles as compared to other p38 proteins in signal transduction. Recent studies showed that, in addition to inflammation, p38γ metabolic signaling is involved in physiological exercise and in pathogenesis of cancer, diabetes, and Alzheimer’s disease, indicating its potential as a therapeutic target. p38γphosphorylates at least 19 substrates through which p38γ activity is further modified to regulate life-important cellular processes such as proliferation, differentiation, cell death, and transformation, thereby impacting biological outcomes of p38γ-driven pathogenesis. P38γ signaling is characterized by its unique reciprocal regulation with its specific phosphatase PTPH1 and by its direct binding to promoter DNAs, leading to transcriptional activation of targets including cancer-like stem cell drivers. This paper will review recent findings about p38γ inflammation and metabolic signaling in physiology and diseases. Moreover, we will discuss the progress in the development of p38γ-specific pharmacological inhibitors for therapeutic intervention in disease prevention and treatment by targeting the p38γ signaling network. MDPI 2023-06-21 /pmc/articles/PMC10341180/ /pubmed/37443708 http://dx.doi.org/10.3390/cells12131674 Text en © 2023 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
Qi, Xiao-Mei
Chen, Guan
p38γ MAPK Inflammatory and Metabolic Signaling in Physiology and Disease
title p38γ MAPK Inflammatory and Metabolic Signaling in Physiology and Disease
title_full p38γ MAPK Inflammatory and Metabolic Signaling in Physiology and Disease
title_fullStr p38γ MAPK Inflammatory and Metabolic Signaling in Physiology and Disease
title_full_unstemmed p38γ MAPK Inflammatory and Metabolic Signaling in Physiology and Disease
title_short p38γ MAPK Inflammatory and Metabolic Signaling in Physiology and Disease
title_sort p38γ mapk inflammatory and metabolic signaling in physiology and disease
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10341180/
https://www.ncbi.nlm.nih.gov/pubmed/37443708
http://dx.doi.org/10.3390/cells12131674
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