Document Details

Document Type:   Dissertation
Title:   Diverse Roles of PKCalpha in Vascular Smooth Muscle Contraction
Author:   Ava Caudill Dykes
College:   Joan C. Edwards School of Medicine
Degree Program:   Biomedical Sciences, Ph.D.
Degree:   Doctor of Philosophy
Committee Director:   Gary L. Wright
Document Availability:   Document available for World-Wide access.
Date of Defense:   5/23/2006

A complete understanding of the mechanisms underlying smooth muscle contractility has proven elusive due to the many interacting factors thought to influence contractile behavior in this muscle type. One such factor, protein kinase C (PKC), is proposed to play a central role in both the activation and modulation of smooth muscle contraction. PKC is activated through a G-protein coupled receptor and is subsequently translocated to its site of action. Although the mechanisms regulating PKC site specific translocation are not completely understood, it is thought that this process is essential for PKC specificity of action within the cell. In chapter II we discuss our research demonstrating a PKC/-tubulin relationship in the contracting smooth muscle cell. Here, we show for the first time that PKC translocation is dependent on an intact system of microtubules and propose the hypothesis of microtubular involvement in PKC translocation. Activation of PKC in contracting smooth muscle is thought to result in the phosphorylation of several proteins which could be important in contraction. One such protein, calponin, is known to influence smooth muscle contractility but its mechanism of action is not clear. In chapter III, we discuss our research showing the formation of a PKC/calponin complex in contracting smooth muscle with associated losses in -actin stress fibers and cytoskeletal remodeling. Based on this work, we propose that calponin plays a major role in the stabilization of stress fibers and that the release from calponin cross-linking of actin filaments provides a mechanism enabling actin filament sliding and subsequent cytoskeletal remodeling.  

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