title: Diversity and plasticity in signaling pathways that regulate smooth muscle responsiveness: Paradigms and paradoxes for the myosin phosphatase, the master regulator of smooth muscle contraction.
abstract: A hallmark of smooth muscle cells is their ability to adapt their functions to meet temporal and chronic fluctuations in their demands. These functions include force development and growth. Understanding the mechanisms underlying the functional plasticity of smooth muscles, the major constituent of organ walls, is fundamental to elucidating pathophysiological rationales of failures of organ functions. Also, the knowledge is expected to facilitate devising innovative strategies that more precisely monitor and normalize organ functions by targeting individual smooth muscles. Evidence has established a current paradigm that the myosin light chain phosphatase (MLCP) is a master regulator of smooth muscle responsiveness to stimuli. Cellular MLCP activity is negatively and positively regulated in response to G-protein activation and cAMP/cGMP production, respectively, through the MYPT1 regulatory subunit and an endogenous inhibitor protein named CPI-17. In this article we review the outcomes from two decade of research on the CPI-17 signaling and discuss emerging paradoxes in the view of signaling pathways regulating smooth muscle functions through MLCP.
authors.affiliation: Department of Molecular Physiology and Biophysics, Sidney Kimmel Medical College at Thomas Jefferson University and Sidney Kimmel Cancer Center, 1020 Locust Street, Philadelphia, PA19107, USA.
authors.forename: Masumi
authors.initials: M
authors.lastname: Eto
authors.forename: Toshio
authors.initials: T
authors.lastname: Kitazawa
mesh_terms: D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D009119:Muscle Contraction / Q000235:genetics*; D009124:Muscle Proteins; D009129:Muscle Tonus / Q000235:genetics; D009130:Muscle, Smooth / Q000502:physiology*; D043263:Myosin-Light-Chain Phosphatase / Q000378:metabolism / Q000502:physiology*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism / Q000502:physiology; D010766:Phosphorylation; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D054460:rho-Associated Kinases / Q000502:physiology
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; C107507:PPP1R14A protein, human; D000242:Cyclic AMP; D054460:rho-Associated Kinases; D010749:Phosphoprotein Phosphatases; D043263:Myosin-Light-Chain Phosphatase; C490372:PPP1R12A protein, human; D019204:GTP-Binding Proteins; D006152:Cyclic GMP; D002118:Calcium