Roles and regulation of protein phosphatase 2A (PP2A) in the heart.

Roles and regulation of protein phosphatase 2A (PP2A) in the heart.
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DOI:
10.1016/j.yjmcc.2016.11.003
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发表时间:
2016-12
影响因子:
5
通讯作者:
Mohler PJ
Mohler PJ
中科院分区:
医学2区
文献类型:
--
作者:
Lubbers ER;Mohler PJ

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可逆的蛋白质磷酸化对于多种心脏过程至关重要,包括兴奋-收缩耦合、Ca2+处理、细胞代谢、肌丝调节和细胞间通讯。虽然与肾上腺素能信号传导升高相关的激酶途径在过去的半个世纪中一直是心血管领域的主要焦点,但新的发现支持蛋白磷酸酶在健康和疾病中的关键作用。蛋白磷酸酶 2A (PP2A) 是一种中心心脏磷酸酶,可通过许多靶分子调节多种心肌细胞功能。值得注意的是,已经进化出多种机制来动态调节 PP2A 功能,包括 PP2A 全酶群的组成、磷酸化、甲基化和定位的调节。此外,PP2A 功能调节的异常可能会导致心脏病理生理学。总之,PP2A 是健康和疾病中的关键调节分子,在心脏中具有无数的靶标。基于其独特的结构、定位和调节特性,PP2A 亚基代表了调节心血管疾病中肾上腺素能信号传导改变的令人兴奋的治疗靶点。
Reversible protein phosphorylation is central to a variety of cardiac processes including excitation-contraction coupling, Ca2+ handling, cell metabolism, myofilament regulation, and cell-cell communication. While kinase pathways linked with elevated adrenergic signaling have been a major focus for the cardiovascular field over the past half century, new findings support the critical role of protein phosphatases in both health and disease. Protein phosphatase 2A (PP2A) is a central cardiac phosphatase that regulates diverse myocyte functions through a host of target molecules. Notably, multiple mechanisms have evolved to dynamically tune PP2A function, including modulation of the composition, phosphorylation, methylation, and localization of PP2A holoenzyme populations. Further, aberrations in this regulation of PP2A function may contribute to cardiac pathophysiology. In summary, PP2A is a critical regulatory molecule in both health and disease, with a myriad of targets in heart. Based on their unique structure, localization, and regulatory properties, PP2A subunits represent exciting therapeutic targets to modulate altered adrenergic signaling in cardiovascular disease.
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