Research Assistant Professor
P21 activated kinase-1 (Pak1) is a serine/threonine protein kinase and a key player in a signaling cascade consisting of large/small G proteins and a protein phosphatase PP2A. Pak1 is abundantly expressed in different regions of the heart. We have demonstrated that Pak1 induces dephosphorylation of cTnI and myosin binding protein C (MyBP-C) in ventricle myocytes, and myosin regulatory light chain in endothelial cells through up-regulation of PP2A. Pak1 regulates myofilament cross-bridge cycling in ventricle myocytes and ion channel activities in sino-atrial (SA) nodal cells. It represses electrical current generated by L-type Ca 2+ channel and delayed rectifier potassium channels in the presence of isoproterenol in the pacemaker cells. Activation of Pak1 antagonizes thrombin initiated barrier dysfunction in endothelial cells. Currently, I employ animal models with heart specific expression and knock-out of Pak1 to observe its functional effects related to heart failure, arrhythmia, ischemia-reperfusion damage and other cardiac conditions. Another line of my studies is to identify the molecular mechanism whereby some small molecules, such as sphingosines, activate Pak1 in vitro and in vivo . The long-term goal of my studies is to develop a novel therapeutics for major cardiovascular diseases.
Publications:
Ke Y, Wang L, Pyle WG, de Tombe PP and Solaro RJ. 2004. Intracellular Localization and Functional Effects of P21 activated Kinae-1 (Pak1) in Cardiac Myocytes. Circulation Research, 94:194-200.
Ke Y, Lei M, Collins TP, Rakovic S, Mattick PA, Yamasaki M, Brodie MS, Terrar DA and Solaro RJ. 2007. Regulation of L-type calcium channel and delayed rectifier potassium channel activity by p21-activated kinase-1 in guinea pig sinoatrial node pacemaker cells. Circ Res 100: 1317-27
Ke Y*, Lum H, Solaro RJ. 2007. Inhibition of endothelial barrier dysfunction by P21-activated kinase-1. Can J Physiol Pharmacol 85: 281-8 (*author for correspondence)
Sheehan KA, Ke Y, Solaro RJ. 2007. P21 Activated Kinase-1 and its Role in Integrated Regulation of Cardiac Contractility. Am J Physiol Regul Integr Comp Physiol 293: R963-97
Lei M, Ke Y*, Solaro RJ. 2007. Pak1: steps towards understanding the regulatory mechanism of pacemaker function of the heart (Editorial). Future Cardiology. 3 (5) (author for correspondence)
Send Message to: yke@uic.edu
03/13/08