丝氨酸-苏氨酸蛋白磷酸酶调节心律失常相关疾病中 Cx43 的去磷酸化作用。
Serine-threonine protein phosphatase regulation of Cx43 dephosphorylation in arrhythmogenic disorders.
机构信息
Department of Physiology & Biophysics, Rush University, Chicago, IL, United States of America.
Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States of America.
出版信息
Cell Signal. 2021 Oct;86:110070. doi: 10.1016/j.cellsig.2021.110070. Epub 2021 Jul 2.
Abstract
Regulation of cell-to-cell communication in the heart by the gap junction protein Connexin43 (Cx43) involves modulation of Cx43 phosphorylation state by protein kinases, and dephosphorylation by protein phosphatases. Dephosphorylation of Cx43 has been associated with impaired intercellular coupling and enhanced arrhythmogenesis in various pathologic states. While there has been extensive study of the protein kinases acting on Cx43, there has been limited studies of the protein phosphatases that may underlie Cx43 dephosphorylation. The focus of this review is to introduce serine-threonine protein phosphatase regulation of Cx43 phosphorylation state and cell-to-cell communication, and its impact on arrhythmogenesis in the setting of chronic heart failure and myocardial ischemia, as well as on atrial fibrillation. We also discuss the therapeutic potential of modulating protein phosphatases to treat arrhythmias in these clinical settings.
摘要
间隙连接蛋白 43（Cx43）通过调节细胞间通讯，参与心脏细胞间通讯的调控，这涉及蛋白激酶对 Cx43 磷酸化状态的调节，以及蛋白磷酸酶的去磷酸化。Cx43 的去磷酸化与各种病理状态下细胞间耦联受损和心律失常发生增强有关。虽然已经对作用于 Cx43 的蛋白激酶进行了广泛的研究，但对可能导致 Cx43 去磷酸化的蛋白磷酸酶的研究却很有限。本篇综述的重点是介绍丝氨酸-苏氨酸蛋白磷酸酶对 Cx43 磷酸化状态和细胞间通讯的调节，以及其在慢性心力衰竭和心肌缺血以及心房颤动时对心律失常发生的影响。我们还讨论了在这些临床情况下调节蛋白磷酸酶治疗心律失常的治疗潜力。
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