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Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia
Somlyo, Andrew P., and Avril V. Somlyo. Ca2+ Sensitivity of Smooth Muscle and Nonmuscle Myosin II: Modulated by G Proteins, Kinases, and Myosin Phosphatase. Physiol Rev 83: 1325-1358, 2003; 10.1152/physrev.00023.2003.— Ca2+ sensitivity of smooth muscle and nonmuscle myosin II reflects the ratio of activities of myosin light-chain kinase (MLCK) to myosin light-chain phosphatase (MLCP) and is a major, regulated determinant of numerous cellular processes. We conclude that the majority of phenotypes attributed to the monomeric G protein RhoA and mediated by its effector, Rho-kinase (ROK), reflect Ca2+ sensitization: inhibition of myosin II dephosphorylation in the presence of basal (Ca2+ dependent or independent) or increased MLCK activity. We outline the pathway from receptors through trimeric G proteins (G
q, G12, G13) to activation, by guanine nucleotide exchange factors (GEFs), from GDP · RhoA · GDI to GTP · RhoA and hence to ROK through a mechanism involving association of GEF, RhoA, and ROK in multimolecular complexes at the lipid cell membrane. Specific domains of GEFs interact with trimeric G proteins, and some GEFs are activated by Tyr kinases whose inhibition can inhibit Rho signaling. Inhibition of MLCP, directly by ROK or by phosphorylation of the phosphatase inhibitor CPI-17, increases phosphorylation of the myosin II regulatory light chain and thus the activity of smooth muscle and nonmuscle actomyosin ATPase and motility. We summarize relevant effects of p21-activated kinase, LIM-kinase, and focal adhesion kinase. Mechanisms of Ca2+ desensitization are outlined with emphasis on the antagonism between cGMP-activated kinase and the RhoA/ROK pathway. We suggest that the RhoA/ROK pathway is constitutively active in a number of organs under physiological conditions; its aberrations play major roles in several disease states, particularly impacting on Ca2+ sensitization of smooth muscle in hypertension and possibly asthma and on cancer neoangiogenesis and cancer progression. It is a potentially important therapeutic target and a subject for translational research.
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 K. Takeya, K. Loutzenhiser, M. Shiraishi, R. Loutzenhiser, and M. P. Walsh A highly sensitive technique to measure myosin regulatory light chain phosphorylation: the first quantification in renal arterioles Am J Physiol Renal Physiol, June 1, 2008; 294(6): F1487 - F1492. [Abstract] [Full Text] [PDF]
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L. Chen, J. J. Zhang, and X.-Y. Huang cAMP Inhibits Cell Migration by Interfering with Rac-induced Lamellipodium Formation J. Biol. Chem., May 16, 2008; 283(20): 13799 - 13805. [Abstract] [Full Text] [PDF]
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W. G. Wier, M. A. Rizzo, H. Raina, and J. Zacharia A technique for simultaneous measurement of Ca2+, FRET fluorescence and force in intact mouse small arteries J. Physiol., May 15, 2008; 586(10): 2437 - 2443. [Abstract] [Full Text] [PDF]
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 H. Yasue, Y. Mizuno, E. Harada, T. Itoh, H. Nakagawa, M. Nakayama, H. Ogawa, S. Tayama, T. Honda, S. Hokimoto, et al. Effects of a 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitor, Fluvastatin, on Coronary Spasm After Withdrawal of Calcium-Channel Blockers J. Am. Coll. Cardiol., May 6, 2008; 51(18): 1742 - 1748. [Abstract] [Full Text] [PDF]
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P. Delmotte and M. J. Sanderson Effects of Albuterol Isomers on the Contraction and Ca2+ Signaling of Small Airways in Mouse Lung Slices Am. J. Respir. Cell Mol. Biol., May 1, 2008; 38(5): 524 - 531. [Abstract] [Full Text] [PDF]
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P. J. Dougherty, M. J. Davis, D. C. Zawieja, and M. Muthuchamy Calcium sensitivity and cooperativity of permeabilized rat mesenteric lymphatics Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2008; 294(5): R1524 - R1532. [Abstract] [Full Text] [PDF]
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H. H. Wang, H. Tanaka, X. Qin, T. Zhao, L.-H. Ye, T. Okagaki, T. Katayama, A. Nakamura, R. Ishikawa, S. E. Thatcher, et al. Blebbistatin inhibits the chemotaxis of vascular smooth muscle cells by disrupting the myosin II-actin interaction Am J Physiol Heart Circ Physiol, May 1, 2008; 294(5): H2060 - H2068. [Abstract] [Full Text] [PDF]
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B. R. S. Broughton, B. R. Walker, and T. C. Resta Chronic hypoxia induces Rho kinase-dependent myogenic tone in small pulmonary arteries Am J Physiol Lung Cell Mol Physiol, April 1, 2008; 294(4): L797 - L806. [Abstract] [Full Text] [PDF]
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Y. Chiba, J. Arima, H. Sakai, and M. Misawa Lovastatin inhibits bronchial hyperresponsiveness by reducing RhoA signaling in rat allergic asthma Am J Physiol Lung Cell Mol Physiol, April 1, 2008; 294(4): L705 - L713. [Abstract] [Full Text] [PDF]
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N. Villalba, E. Stankevicius, U. Simonsen, and D. Prieto Rho kinase is involved in Ca2+ entry of rat penile small arteries Am J Physiol Heart Circ Physiol, April 1, 2008; 294(4): H1923 - H1932. [Abstract] [Full Text] [PDF]
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J. T. Smyth, W. I. DeHaven, G. S. Bird, and J. W. Putney Jr Ca2+-store-dependent and -independent reversal of Stim1 localization and function J. Cell Sci., March 15, 2008; 121(6): 762 - 772. [Abstract] [Full Text] [PDF]
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S. Rattan and C. A. Patel Selectivity of ROCK inhibitors in the spontaneously tonic smooth muscle Am J Physiol Gastrointest Liver Physiol, March 1, 2008; 294(3): G687 - G693. [Abstract] [Full Text] [PDF]
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C. Morin, C. Guibert, M. Sirois, V. Echave, M. M. Gomes, and E. Rousseau Effects of {omega}-hydroxylase product on distal human pulmonary arteries Am J Physiol Heart Circ Physiol, March 1, 2008; 294(3): H1435 - H1443. [Abstract] [Full Text] [PDF]
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P. D. Smith, S. E. Brett, K. D. Luykenaar, S. L. Sandow, S. P. Marrelli, E. J. Vigmond, and D. G. Welsh KIR channels function as electrical amplifiers in rat vascular smooth muscle J. Physiol., February 15, 2008; 586(4): 1147 - 1160. [Abstract] [Full Text] [PDF]
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D. Umeda, S. Yano, K. Yamada, and H. Tachibana Green Tea Polyphenol Epigallocatechin-3-gallate Signaling Pathway through 67-kDa Laminin Receptor J. Biol. Chem., February 8, 2008; 283(6): 3050 - 3058. [Abstract] [Full Text] [PDF]
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C. Morin, M. Sirois, V. Echave, M. M. Gomes, and E. Rousseau EET Displays Anti-Inflammatory Effects in TNF-{alpha} Stimulated Human Bronchi: Putative Role of CPI-17 Am. J. Respir. Cell Mol. Biol., February 1, 2008; 38(2): 192 - 201. [Abstract] [Full Text] [PDF]
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S. K. Sarna Are interstitial cells of Cajal plurifunction cells in the gut? Am J Physiol Gastrointest Liver Physiol, February 1, 2008; 294(2): G372 - G390. [Abstract] [Full Text] [PDF]
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P. J. McNamara, P. Murthy, C. Kantores, L. Teixeira, D. Engelberts, T. van Vliet, B. P. Kavanagh, and R. P. Jankov Acute vasodilator effects of Rho-kinase inhibitors in neonatal rats with pulmonary hypertension unresponsive to nitric oxide Am J Physiol Lung Cell Mol Physiol, February 1, 2008; 294(2): L205 - L213. [Abstract] [Full Text] [PDF]
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R. Srinivasan, S. Forman, R. A. Quinlan, J. Ohanian, and V. Ohanian Regulation of contractility by Hsp27 and Hic-5 in rat mesenteric small arteries Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H961 - H969. [Abstract] [Full Text] [PDF]
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K. J. Allahdadi, L. C. Duling, B. R. Walker, and N. L. Kanagy Eucapnic intermittent hypoxia augments endothelin-1 vasoconstriction in rats: role of PKC{delta} Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H920 - H927. [Abstract] [Full Text] [PDF]
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M. F. Navedo, M. Nieves-Cintron, G. C. Amberg, C. Yuan, V. S. Votaw, W. J. Lederer, G. S. McKnight, and L. F. Santana AKAP150 Is Required for Stuttering Persistent Ca2+ Sparklets and Angiotensin II-Induced Hypertension Circ. Res., February 1, 2008; 102(2): e1 - e11. [Abstract] [Full Text] [PDF]
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G. A. Knock, Y. Shaifta, V. A. Snetkov, B. Vowles, S. Drndarski, J. P.T. Ward, and P. I. Aaronson Interaction between src family kinases and rho-kinase in agonist-induced Ca2+-sensitization of rat pulmonary artery Cardiovasc Res, February 1, 2008; 77(3): 570 - 579. [Abstract] [Full Text] [PDF]
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M. A. Conti and R. S. Adelstein Nonmuscle myosin II moves in new directions J. Cell Sci., January 1, 2008; 121(1): 11 - 18. [Abstract] [Full Text] [PDF]
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 I. Mueed, T. Tazzeo, C. Liu, E. Pertens, Y. Zhang, I. Cybulski, L. Semelhago, J. Noora, A. Lamy, K. Teoh, et al. Isoprostanes constrict human radial artery by stimulation of thromboxane receptors, Ca2+ release, and RhoA activation J. Thorac. Cardiovasc. Surg., January 1, 2008; 135(1): 131 - 138. [Abstract] [Full Text] [PDF]
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 M. J. Sanderson, P. Delmotte, Y. Bai, and J. F. Perez-Zogbhi Regulation of Airway Smooth Muscle Cell Contractility by Ca2+ Signaling and Sensitivity Proceedings of the ATS, January 1, 2008; 5(1): 23 - 31. [Abstract] [Full Text] [PDF]
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