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

• Published in: The Journal of physiology 2000-01, Vol.522 (2), p.177-185
• Main Authors: Somlyo, Andrew P., Somlyo, Avril V.
• Format: Article
• Language: English
• Subjects: 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; rho-Associated Kinases; Signal Transduction - physiology; Topical Review
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1111/j.1469-7793.2000.t01-2-00177.x

We here review mechanisms that can regulate the activity of myosin II, in smooth muscle and non-muscle cells, by modulating the Ca 2+ sensitivity of myosin regulatory light chain (RLC) phosphorylation. The major mechanism of Ca 2+ 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 Ca 2+ sensitization. Ca 2+ 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.