Redox Regulation of cAMP-Dependent Protein Kinase and Its Role in Health and Disease

Protein kinase A (PKA) is a key regulator of cellular signaling that regulates key physiological processes such as metabolism, cell proliferation, and neuronal function. While its activation by the second messenger 3′,5′-cyclic adenosine triphosphate (cAMP) is well characterized, recent research hig...

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Main Authors: Ese S. Ekhator, Marco Fazzari, Robert H. Newman
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Life
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Online Access:https://www.mdpi.com/2075-1729/15/4/655
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author Ese S. Ekhator
Marco Fazzari
Robert H. Newman
author_facet Ese S. Ekhator
Marco Fazzari
Robert H. Newman
author_sort Ese S. Ekhator
collection DOAJ
description Protein kinase A (PKA) is a key regulator of cellular signaling that regulates key physiological processes such as metabolism, cell proliferation, and neuronal function. While its activation by the second messenger 3′,5′-cyclic adenosine triphosphate (cAMP) is well characterized, recent research highlights additional regulatory mechanisms, particularly oxidative post-translational modifications, that influence PKA’s structure, activity, and substrate specificity. Both the regulatory and catalytic subunits of PKA are susceptible to redox modifications, which have been shown to play important roles in the regulation of key cellular functions, including cardiac contractility, lipid metabolism, and the immune response. Likewise, redox-dependent modulation of PKA signaling has been implicated in numerous diseases, including cardiovascular disorders, diabetes, and neurodegenerative conditions, making it a potential therapeutic target. However, the mechanisms of crosstalk between redox- and PKA-dependent signaling remain poorly understood. This review examines the structural and functional regulation of PKA, with a focus on redox-dependent modifications and their impact on PKA-dependent signaling. A deeper understanding of these mechanisms may provide new strategies for targeting oxidative stress in disease and restoring balanced PKA signaling in cells.
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spelling doaj-art-478750d282974f668581f42e9b4b7d2d2025-08-20T02:28:15ZengMDPI AGLife2075-17292025-04-0115465510.3390/life15040655Redox Regulation of cAMP-Dependent Protein Kinase and Its Role in Health and DiseaseEse S. Ekhator0Marco Fazzari1Robert H. Newman2Department of Biology, North Carolina A&T State University, Greensboro, NC 27411, USADepartment of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USADepartment of Biology, North Carolina A&T State University, Greensboro, NC 27411, USAProtein kinase A (PKA) is a key regulator of cellular signaling that regulates key physiological processes such as metabolism, cell proliferation, and neuronal function. While its activation by the second messenger 3′,5′-cyclic adenosine triphosphate (cAMP) is well characterized, recent research highlights additional regulatory mechanisms, particularly oxidative post-translational modifications, that influence PKA’s structure, activity, and substrate specificity. Both the regulatory and catalytic subunits of PKA are susceptible to redox modifications, which have been shown to play important roles in the regulation of key cellular functions, including cardiac contractility, lipid metabolism, and the immune response. Likewise, redox-dependent modulation of PKA signaling has been implicated in numerous diseases, including cardiovascular disorders, diabetes, and neurodegenerative conditions, making it a potential therapeutic target. However, the mechanisms of crosstalk between redox- and PKA-dependent signaling remain poorly understood. This review examines the structural and functional regulation of PKA, with a focus on redox-dependent modifications and their impact on PKA-dependent signaling. A deeper understanding of these mechanisms may provide new strategies for targeting oxidative stress in disease and restoring balanced PKA signaling in cells.https://www.mdpi.com/2075-1729/15/4/655protein kinasecAMP-dependent protein kinase (PKA)reactive oxygen species (ROS)oxidationredox-dependent signalingglutathionylation
spellingShingle Ese S. Ekhator
Marco Fazzari
Robert H. Newman
Redox Regulation of cAMP-Dependent Protein Kinase and Its Role in Health and Disease
Life
protein kinase
cAMP-dependent protein kinase (PKA)
reactive oxygen species (ROS)
oxidation
redox-dependent signaling
glutathionylation
title Redox Regulation of cAMP-Dependent Protein Kinase and Its Role in Health and Disease
title_full Redox Regulation of cAMP-Dependent Protein Kinase and Its Role in Health and Disease
title_fullStr Redox Regulation of cAMP-Dependent Protein Kinase and Its Role in Health and Disease
title_full_unstemmed Redox Regulation of cAMP-Dependent Protein Kinase and Its Role in Health and Disease
title_short Redox Regulation of cAMP-Dependent Protein Kinase and Its Role in Health and Disease
title_sort redox regulation of camp dependent protein kinase and its role in health and disease
topic protein kinase
cAMP-dependent protein kinase (PKA)
reactive oxygen species (ROS)
oxidation
redox-dependent signaling
glutathionylation
url https://www.mdpi.com/2075-1729/15/4/655
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AT marcofazzari redoxregulationofcampdependentproteinkinaseanditsroleinhealthanddisease
AT roberthnewman redoxregulationofcampdependentproteinkinaseanditsroleinhealthanddisease