? Three recent breakthroughs of the parent Program Project Grant, entitled """"""""Molecular Mechanism of Smooth Muscle Regulation"""""""" (P01-AR41637-12) has prompted the need of an additional core to put the biochemical findings in a physiological context: (a) the successful knockout of smooth muscle caldesmon (h-CaD) in mice; (b) the determination of the crystal structure of myosin phosphatase; and (c) the newly developed constructs of MYPT1. A new Physiological Core (Core C) is proposed to serve this purpose. Dr. Kitazawa will lead Core C to address important issues in smooth muscle regulation by analyzing the physiological parameters (including the blood pressure, Ca2+ signals, isometric contraction, shortening velocity, stiffness, and protein phosphorylation) of smooth muscle tissues isolated from the h-CaD-null and the wild-type animals, and by introducing recombinant proteins and synthetic peptides of myosin phosphatase, based on its 3D structure, into smooth muscle tissues. The information derived from this Core will complement and greatly enhance the current program, in particular the projects concerning the function/structure of caldesmon (Subproject II) and myosin phosphatase (Subprojects I and III). It will also provide more intimate clues for a better understanding about human diseases related to smooth muscles. ? ?
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