| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
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.
This article has been cited by other articles:
|
|
 |
|
  C. Morin, M. Sirois, V. Echave, and E. Rousseau CPI-17 Silencing-Reduced Responsiveness in Control and TNF-{alpha}-Treated Human Bronchi Am. J. Respir. Cell Mol. Biol., December 1, 2008; 39(6): 638 - 643. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Chi, Y. Zhou, S. Vedamoorthyrao, G. J. Babu, and M. Periasamy Ablation of smooth muscle myosin heavy chain SM2 increases smooth muscle contraction and results in postnatal death in mice PNAS, November 25, 2008; 105(47): 18614 - 18618. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Ponsaerts, C. D'hondt, G. Bultynck, S. P. Srinivas, J. Vereecke, and B. Himpens The Myosin II ATPase Inhibitor Blebbistatin Prevents Thrombin-Induced Inhibition of Intercellular Calcium Wave Propagation in Corneal Endothelial Cells Invest. Ophthalmol. Vis. Sci., November 1, 2008; 49(11): 4816 - 4827. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Badejo Jr., J. S. Dhaliwal, D. B. Casey, T. B. Gallen, A. J. Greco, and P. J. Kadowitz Analysis of pulmonary vasodilator responses to the Rho-kinase inhibitor fasudil in the anesthetized rat Am J Physiol Lung Cell Mol Physiol, November 1, 2008; 295(5): L828 - L836. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Gao, A. D. Portugal, J. Liu, S. Negash, W. Zhou, J. Tian, R. Xiang, L. D. Longo, and J. U. Raj Preservation of cGMP-induced relaxation of pulmonary veins of fetal lambs exposed to chronic high altitude hypoxia: role of PKG and Rho kinase Am J Physiol Lung Cell Mol Physiol, November 1, 2008; 295(5): L889 - L896. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Zhang, R. Maddala, and P. V. Rao Novel molecular insights into RhoA GTPase-induced resistance to aqueous humor outflow through the trabecular meshwork Am J Physiol Cell Physiol, November 1, 2008; 295(5): C1057 - C1070. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Berridge Smooth muscle cell calcium activation mechanisms J. Physiol., November 1, 2008; 586(21): 5047 - 5061. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Sims, T. Chrones, and H. G. Preiksaitis Calcium Sensitization in Human Esophageal Muscle: Role for RhoA Kinase in Maintenance of Lower Esophageal Sphincter Tone J. Pharmacol. Exp. Ther., October 1, 2008; 327(1): 178 - 186. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. M. Goeckeler, P. C. Bridgman, and R. B. Wysolmerski Nonmuscle myosin II is responsible for maintaining endothelial cell basal tone and stress fiber integrity Am J Physiol Cell Physiol, October 1, 2008; 295(4): C994 - C1006. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Tourneux, M. Chester, T. Grover, and S. H. Abman Fasudil inhibits the myogenic response in the fetal pulmonary circulation Am J Physiol Heart Circ Physiol, October 1, 2008; 295(4): H1505 - H1513. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Weinmeister, R. Lukowski, S. Linder, C. Traidl-Hoffmann, L. Hengst, F. Hofmann, and R. Feil Cyclic Guanosine Monophosphate-dependent Protein Kinase I Promotes Adhesion of Primary Vascular Smooth Muscle Cells Mol. Biol. Cell, October 1, 2008; 19(10): 4434 - 4441. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. M. Seok, I. Baek, Y.-H. Kim, Y.-S. Jeong, I.-J. Lee, D. H. Shin, Y. H. Hwang, and I. K. Kim Isoflavone Attenuates Vascular Contraction through Inhibition of the RhoA/Rho-Kinase Signaling Pathway J. Pharmacol. Exp. Ther., September 1, 2008; 326(3): 991 - 998. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M Hennenberg, J Trebicka, T Sauerbruch, and J Heller Mechanisms of extrahepatic vasodilation in portal hypertension Gut, September 1, 2008; 57(9): 1300 - 1314. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. J. Fairbank, S. C. Connolly, J. D. MacKinnon, K. Wehry, L. Deng, and G. N. Maksym Airway smooth muscle cell tone amplifies contractile function in the presence of chronic cyclic strain Am J Physiol Lung Cell Mol Physiol, September 1, 2008; 295(3): L479 - L488. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. R. Kim, C. Gallant, P. C. Leavis, S. J. Gunst, and K. G. Morgan Cytoskeletal remodeling in differentiated vascular smooth muscle is actin isoform dependent and stimulus dependent Am J Physiol Cell Physiol, September 1, 2008; 295(3): C768 - C778. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Gunst and W. Zhang Actin cytoskeletal dynamics in smooth muscle: a new paradigm for the regulation of smooth muscle contraction Am J Physiol Cell Physiol, September 1, 2008; 295(3): C576 - C587. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.C. Montezano, G.E. Callera, A. Yogi, Y. He, R.C. Tostes, G. He, E.L. Schiffrin, and R.M. Touyz Aldosterone and Angiotensin II Synergistically Stimulate Migration in Vascular Smooth Muscle Cells Through c-Src-Regulated Redox-Sensitive RhoA Pathways Arterioscler. Thromb. Vasc. Biol., August 1, 2008; 28(8): 1511 - 1518. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Mizuno, E. Isotani, J. Huang, H. Ding, J. T. Stull, and K. E. Kamm Myosin light chain kinase activation and calcium sensitization in smooth muscle in vivo Am J Physiol Cell Physiol, August 1, 2008; 295(2): C358 - C364. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Clarke, S. Forman, J. Pritchett, V. Ohanian, and J. Ohanian Phospholipase C-{delta}1 modulates sustained contraction of rat mesenteric small arteries in response to noradrenaline, but not endothelin-1 Am J Physiol Heart Circ Physiol, August 1, 2008; 295(2): H826 - H834. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Yohannes, J. Chang, G. J. Christ, K. P. Davies, and M. R. Chance Proteomics Analysis Identifies Molecular Targets Related to Diabetes Mellitus-associated Bladder Dysfunction Mol. Cell. Proteomics, July 1, 2008; 7(7): 1270 - 1285. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Schaafsma, I. S. T. Bos, A. B. Zuidhof, J. Zaagsma, and H. Meurs The inhaled Rho kinase inhibitor Y-27632 protects against allergen-induced acute bronchoconstriction, airway hyperresponsiveness, and inflammation Am J Physiol Lung Cell Mol Physiol, July 1, 2008; 295(1): L214 - L219. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B Wojciak-Stothard New drug targets for pulmonary hypertension: Rho GTPases in pulmonary vascular remodelling Postgrad. Med. J., July 1, 2008; 84(993): 348 - 353. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kapustina, G. E. Weinreb, N. Costigliola, Z. Rajfur, K. Jacobson, and T. C. Elston Mechanical and Biochemical Modeling of Cortical Oscillations in Spreading Cells Biophys. J., June 15, 2008; 94(12): 4605 - 4620. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. V. Rao, Y. K. Peterson, T. Inoue, and P. J. Casey Effects of Pharmacologic Inhibition of Protein Geranylgeranyltransferase Type I on Aqueous Humor Outflow through the Trabecular Meshwork Invest. Ophthalmol. Vis. Sci., June 1, 2008; 49(6): 2464 - 2471. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
I. Wang, A. Z. Politi, N. Tania, Y. Bai, M. J. Sanderson, and J. Sneyd A Mathematical Model of Airway and Pulmonary Arteriole Smooth Muscle Biophys. J., March 15, 2008; 94(6): 2053 - 2064. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
R. Leguillette and A.-M. Lauzon Molecular Mechanics of Smooth Muscle Contractile Proteins in Airway Hyperresponsiveness and Asthma Proceedings of the ATS, January 1, 2008; 5(1): 40 - 46. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Schubert, D. Lidington, and S.-S. Bolz The emerging role of Ca2+ sensitivity regulation in promoting myogenic vasoconstriction Cardiovasc Res, January 1, 2008; 77(1): 8 - 18. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Komalavilas, R. B. Penn, C. R. Flynn, J. Thresher, L. B. Lopes, E. J. Furnish, M. Guo, M. A. Pallero, J. E. Murphy-Ullrich, and C. M. Brophy The small heat shock-related protein, HSP20, is a cAMP-dependent protein kinase substrate that is involved in airway smooth muscle relaxation Am J Physiol Lung Cell Mol Physiol, January 1, 2008; 294(1): L69 - L78. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Telezhkin, T. Goecks, A. D. Bonev, G. Osol, and N. I. Gokina Decreased function of voltage-gated potassium channels contributes to augmented myogenic tone of uterine arteries in late pregnancy Am J Physiol Heart Circ Physiol, January 1, 2008; 294(1): H272 - H284. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Padro, E. Pena, M. Garcia-Arguinzonis, V. Llorente-Cortes, and L. Badimon Low-density lipoproteins impair migration of human coronary vascular smooth muscle cells and induce changes in the proteomic profile of myosin light chain Cardiovasc Res, January 1, 2008; 77(1): 211 - 220. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Kass, H. C. Champion, and J. A. Beavo Phosphodiesterase Type 5: Expanding Roles in Cardiovascular Regulation Circ. Res., November 26, 2007; 101(11): 1084 - 1095. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Dhaliwal, D. B. Casey, A. J. Greco, A. M. Badejo Jr., T. B. Gallen, S. N. Murthy, B. D. Nossaman, A. L. Hyman, and P. J. Kadowitz Rho kinase and Ca2+ entry mediate increased pulmonary and systemic vascular resistance in L-NAME-treated rats Am J Physiol Lung Cell Mol Physiol, November 1, 2007; 293(5): L1306 - L1313. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. J. Allahdadi, B. R. Walker, and N. L. Kanagy ROK contribution to endothelin-mediated contraction in aorta and mesenteric arteries following intermittent hypoxia/hypercapnia in rats Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H2911 - H2918. [Abstract] [Full Text] [PDF]
|
|
|
|
