Ekhator Ese S, Fazzari Marco, Newman Robert H
Department of Biology, North Carolina A&T State University, Greensboro, NC 27411, USA.
Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Life (Basel). 2025 Apr 16;15(4):655. doi: 10.3390/life15040655.
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.
蛋白激酶A（PKA）是细胞信号传导的关键调节因子，可调节新陈代谢、细胞增殖和神经元功能等关键生理过程。虽然其由第二信使3'，5'-环磷酸腺苷（cAMP）激活的过程已得到充分表征，但最近的研究突出了其他调节机制，特别是氧化翻译后修饰，这些机制会影响PKA的结构、活性和底物特异性。PKA的调节亚基和催化亚基都易受氧化还原修饰的影响，氧化还原修饰已被证明在调节关键细胞功能（包括心脏收缩力、脂质代谢和免疫反应）中发挥重要作用。同样，PKA信号的氧化还原依赖性调节与包括心血管疾病、糖尿病和神经退行性疾病在内的多种疾病有关，使其成为一个潜在的治疗靶点。然而，氧化还原依赖性信号与PKA依赖性信号之间的串扰机制仍知之甚少。本综述探讨了PKA的结构和功能调节，重点关注氧化还原依赖性修饰及其对PKA依赖性信号传导的影响。对这些机制的更深入理解可能为针对疾病中的氧化应激以及恢复细胞中平衡的PKA信号传导提供新策略。
