835 S. Wolcott Ave., (M/C 901)
Chicago, IL 60612-7342
312-996-7620 phone
312-996-1414 fax
835 S. Wolcott Ave., (M/C 901)
Chicago, IL 60612-7342
312-996-7620 phone
312-996-1414 fax
The well-being of a mammalian heart requires balanced activities of multiple extra- and intra-cellular factors. Permanent break-down of the balance, such as mutations in troponins/tropomyosin and chronicle occlusion of coronary blood flow lead to heart diseases which can often be exacerbated or ameliorated by protein phosphorylation (or de-phosphorylation) induced by signaling molecules on different effectors, especially on those that regulate myofilament activities and Ca 2+ handling. Our current studies focus on interaction between Pak1 (p21 activated kinase-1) and phosphatase PP2A related to protein phosphorylation of cardiac troponin I (cTnI), myosin binding protein-C (MyBP-C), phospholamban (PLB) and L-type Ca 2+ channels, etc. We use a mouse model null for Pak1 to study Pak1 function related to cardiac remodeling and to different cardiac disorders, such as ischemic heart diseases and heart failure. In addition, we study the molecular mechanism whereby Pak1 is turned on and/or off by a group of structurally related small molecules both in vitro and in vivo in order to better understand and develop a novel therapeutics for the major heart diseases.
Pak1 is abundant in different regions of mouse heart (A). Pak1 (B) and PP2A (C) have the same localizations in ventricular muscle sections (images of B and C were taken from A from a region indicated by a white box and an arrow).