Novel insights into mechanisms for Pak1-mediated regulation of cardiac Ca(2+) homeostasis.

Novel insights into mechanisms for Pak1-mediated regulation of cardiac Ca(2+) homeostasis.
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DOI:
10.3389/fphys.2015.00076
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发表时间:
2015
影响因子:
4
通讯作者:
Lei M
Lei M
中科院分区:
医学2区
文献类型:
--
作者:
Wang Y;Tsui H;Bolton EL;Wang X;Huang CL;Solaro RJ;Ke Y;Lei M

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Pak1是由ras相关小g蛋白Cdc42/Rac1调控的高度保守的丝氨酸-苏氨酸蛋白激酶家族的关键成员,最近的一系列研究报道了Pak1在心脏生理和心脏保护中的新作用。先前的研究已经确定Pak1在肥厚重塑的调控中可能导致心力衰竭。本文综述了最近关于Pak1在心脏Ca2+稳态中的作用的研究结果。这些发现确定了Pak1在心肌细胞Ca2+处理中的关键作用,并证明它通过独特的机制发挥作用,包括调节关键Ca2+处理蛋白的转录后活性,包括Ca2+- atp酶SERCA2a的表达,以及参与维持横向(T)管结构的推测可能性。他们强调了Pak1在心肌细胞Ca2+稳态中的重要调节功能,并确定了新的潜在治疗策略,即通过操纵Pak1信号来治疗心脏病,特别是心力衰竭。
A series of recent studies report novel roles for Pak1, a key member of the highly conserved family of serine-threonine protein kinases regulated by Ras-related small G-proteins, Cdc42/Rac1, in cardiac physiology and cardioprotection. Previous studies had identified Pak1 in the regulation of hypertrophic remodeling that could potentially lead to heart failure. This article provides a review of more recent findings on the roles of Pak1 in cardiac Ca2+ homeostasis. These findings identified crucial roles for Pak1 in cardiomyocyte Ca2+ handling and demonstrated that it functions through unique mechanisms involving regulation of the post-transcriptional activity of key Ca2+-handling proteins, including the expression of Ca2+-ATPase SERCA2a, along with the speculative possibility of an involvement in the maintenance of transverse (T)-tubular structure. They highlight important regulatory functions of Pak1 in Ca2+ homeostasis in cardiac cells, and identify novel potential therapeutic strategies directed at manipulation of Pak1 signaling for the management of cardiac disease, particularly heart failure.
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在小鼠中,Pak1 需要通过 SERCA2a 调节来维持心室 Ca2+ 稳态和电生理稳定性。
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