Frontiers in Physiology (Mar 2015)
Novel insights into mechanisms for Pak1-mediated regulation of cardiac Ca2+ homeostasis
Abstract
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 remodelling 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 does so through unique mechanisms involving regulation of the post-transcriptional activity of key Ca2+-handling proteins including the expression of Ca2+-ATPase SERCA2a with the speculative possibility of an involvement in the maintenance of transverse (T)-tubular structure. They highlight important balance and regulatory functions of Pak1 in Ca2+ homeostasis in cardiac cells, and identify novel potential therapeutic strategies directed at manipulation of Pak1 signalling for the management of cardiac disease, particularly heart failure.
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