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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MDPI AG
2025-04-01
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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. |
| format | Article |
| id | doaj-art-478750d282974f668581f42e9b4b7d2d |
| institution | OA Journals |
| issn | 2075-1729 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | MDPI AG |
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| series | Life |
| 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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