title: Novel insights into mechanisms for Pak1-mediated regulation of cardiac Ca(2+) 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 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.
authors: Department of Pharmacology, University of Oxford Oxford, UK.
authors: Yanwen
authors: Y
authors: Wang
authors: Faculty of Life Science, University of Manchester Manchester, UK.
authors: Hoyee
authors: H
authors: Tsui
authors: Department of Pharmacology, University of Oxford Oxford, UK.
authors: Emma L
authors: EL
authors: Bolton
authors: Faculty of Life Science, University of Manchester Manchester, UK.
authors: Xin
authors: X
authors: Wang
authors: Physiological Laboratory, University of Cambridge Cambridge, UK.
authors: Christopher L-H
authors: CL
authors: Huang
authors: Department of Physiology and Biophysics, University of Illinois Chicago, IL, USA.
authors: R John
authors: RJ
authors: Solaro
authors: Department of Physiology and Biophysics, University of Illinois Chicago, IL, USA.
authors: Yunbo
authors: Y
authors: Ke
authors: Department of Pharmacology, University of Oxford Oxford, UK.
authors: Ming
authors: M
authors: Lei
keywords: Ca2+ homeostasis; Pak1; heart