摘要
We review here the novel cardiac protective effects of the multifunctional enzyme, p21-aetivated 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 PAKI 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.
We review here the novel cardiac protective effects of the multifunctional enzyme, p21-aetivated 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 PAKI 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.
基金
The work was supported by the Medical Research Council （G10002647： ML, XW, EJC, RJS, YBK）, the British Heart Foundation （PG/12/21/29473： ML, XW） and the National Natural Science Foundation of China （No. 31171085： ML）, NIH Grant HL 064035 （RJS）, POI HL 062426 （RJS）. The authors thank Dr. Emma Bolton for her proof checking and suggestions for improving the manuscript.
