2014, Volume 8, Issue 4
Frontiers of Medicine >> 2014, Volume 8, Issue 4 doi: 10.1007/s11684-014-0380-9
PAK1 is a novel cardiac protective signaling molecule
1. Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL 60612, USA.
2. Faculty of Life Science, University of Manchester, Manchester M13 9NT, UK.
3. Department of Cardiothoracic Surgery, John Radcliffe Hospital; Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DU, UK.
4. Department of Pharmacology, University of Oxford, Oxford OX1 3QT, UK
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Abstract
We review here the novel cardiac protective effects of the multifunctional enzyme, p21-activated kinase 1 (PAK1), a member of a serine/threonine protein kinase family. Despite the large body of evidence from studies in noncardiac tissue indicating that PAK1 activity is key in the regulation of a number of cellular functions, the role of PAK1 in the heart has only been revealed over the past few years. In this review, we assemble an overview of the recent findings on PAK1 signaling in the heart, particularly its cardiac protective effects. We present a model for PAK1 signaling that provides a mechanism for specifically affecting cardiac cellular processes in which regulation of protein phosphorylation states by protein phosphatase 2A (PP2A) predominates. We discuss the anti-adrenergic and antihypertrophic cardiac protective effects of PAK1, as well as its role in maintaining ventricular Ca2+ homeostasis and electrophysiological stability under physiological, β-adrenergic and hypertrophic stress conditions.
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