Our research has focused on defining signaling pathways that impinge on the contractile apparatus, particularly myosin II, in order to better understand mechanisms by which various stimuli affect the contractile properties of cells and tissues. We have concentrated on muscle as a model system, with substantial focus on smooth muscle, in which robust signaling to affect myosin regulatory light chain phosphorylation regulates contraction and relaxation. Both smooth muscle myosin light chain kinase and phosphatase are subject to regulation as targets themselves of upstream signaling cascades. In our long-standing collaboration, we have applied biochemical, biophysical, cell biological, physiological and mouse genetic approaches to unravel signaling pathways to both myosin kinase and phosphatase in various smooth muscles, including vascular, airway, urogenital and others. Over the past several years we have developed mouse models with regulatory genes (myosin light chain kinase, myosin phosphatase targeting subunit, etc.) floxed for conditional deletion in specific tissues by crosses with transgenic mice expressing Cre recombinase. Because of our combined expertise, we provide a broad background in biophysics, physiology, cell biology, pathophysiology, biochemistry and molecular biology that will support the proposed studies. We have had continuous NIH support for our research programs and have aggressively applied novel scientific developments to provide innovative advancements and new perspectives.