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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 Ca 2+  homeostasis. These findings identified crucial roles for Pak1 in cardiomyocyte Ca 2+  handling and demonstrated that it functions through unique mechanisms involving regulation of the post-transcriptional activity of key Ca 2+ -handling proteins, including the expression of Ca 2+ -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 Ca 2+  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.

Novel insights into mechanisms for Pak1-mediated regulation of cardiac Ca2+ homeostasis