Signal transduction by G-proteins, rho-kinase and protein phosphatase to smooth muscle and non-muscle myosin II

J Physiol. 2000 Jan 15;522 Pt 2(Pt 2):177-85. doi: 10.1111/j.1469-7793.2000.t01-2-00177.x.

Abstract

We here review mechanisms that can regulate the activity of myosin II, in smooth muscle and non-muscle cells, by modulating the Ca2+ sensitivity of myosin regulatory light chain (RLC) phosphorylation. The major mechanism of Ca2+ sensitization of smooth muscle contraction and non-muscle cell motility is through inhibition of the smooth muscle myosin phosphatase (MLCP) that dephosphorylates the RLC in smooth muscle and non-muscle. The active, GTP-bound form of the small GTPase RhoA activates a serine/threonine kinase, Rho-kinase, that phosphorylates the regulatory subunit of MLCP and inhibits phosphatase activity. G-protein-coupled release of arachidonic acid may also contribute to inhibition of MLCP acting, at least in part, through the Rho/Rho-kinase pathway. Protein kinase C(s) activated by phorbol esters and diacylglycerol can also inhibit MLCP by phosphorylating and thereby activating CPI-17, an inhibitor of its catalytic subunit; this mechanism is independent of the Rho/Rho-kinase pathway and plays only a minor, transient role in the G-protein-coupled mechanism of Ca2+ sensitization. Ca2+ sensitization by the Rho/Rho-kinase pathway contributes to the tonic phase of agonist-induced contraction in smooth muscle, and abnormally increased activation of myosin II by this mechanism is thought to play a role in diseases such as high blood pressure and cancer cell metastasis.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • GTP-Binding Proteins / physiology*
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Muscle, Smooth / enzymology
  • Muscle, Smooth / physiology*
  • Myosins / physiology*
  • Phosphoprotein Phosphatases / physiology*
  • Protein Conformation
  • Protein-Serine-Threonine Kinases / physiology*
  • Signal Transduction / physiology*
  • rho-Associated Kinases

Substances

  • Intracellular Signaling Peptides and Proteins
  • Protein-Serine-Threonine Kinases
  • rho-Associated Kinases
  • Phosphoprotein Phosphatases
  • GTP-Binding Proteins
  • Myosins