A new tale of p21 activated protein kinase in the heart:pathophysiology to drug discovery
10.3867/j.issn.1000-3002.2014.04.001
- VernacularTitle:p21活化蛋白激酶与心血管疾病:从病理生理学到药物发现
- Author:
Shoubao WANG
;
Hoyee TSUI
;
Wei LIU
;
Ming LEI
;
Xin WANG
- Publication Type:Journal Article
- Keywords:
p21-activated kinase 1;
serine/ threonine protein kinase;
Pak1 signaIing;
cardiovascuIar disease
- From:
Chinese Journal of Pharmacology and Toxicology
2014;(4):475-483
- CountryChina
- Language:Chinese
-
Abstract:
CardiovascuIar disease is the number one cause for morbidity and mortaIity worIdwide. Possi-biIities for new therapies in the emerging fieId of cardiac signaIIing prompted extensive research on myocardiaI re-modeIIing over the past decades. In this review,we as-sembIe an overview of the recent findings on the muIti-functionaI enzyme,p21-activated kinase 1( Pak1),a member of a serine/ threonine protein kinase famiIy in the heart,particuIarIy its cardiac protective effects. We pres-ent a modeI for Pak1 signaIing that provides a mecha-nism for specificaIIy affecting cardiac ceIIuIar processes. We discuss its cardiac protective effects such as anti-hy-pertrophy,anti-ischaemic injury and roIe in maintaining ventricuIar Ca2+ homeostasis and eIectrophysioIogicaI stabiIity under physioIogicaI, β-adrenergic and hyper-trophic stress conditions.We aIso discuss the potentiaIs of Pak1 activation by naturaIIy occurring sphingosine and its anaIogues FTY720,and bioactive peptides designed to diminish Pak1 auto-inhibition as noveI thera-peutics for major cardiovascuIar diseases.