New Angle of View on the Role of Rho/Rho Kinase Pathway in Human Diseases
Abstract
Rho-kinase is an effector molecule of RhoA, a monomeric GTP-binding protein, and causes Ca2+ sensitization through inactivation of myosin phosphatase. The major physiological functions of Rho/Rho-kinase cascade include contraction, proliferation and migration in cells.There are some excellent reviews about Rho/Rho-kinase signal pathway, most of which focus on the specific proteins of the pathway including some upstream regulators and its final effects. But few articles cover signal pathways that can activate the signaling concerned, and/or the pathways that Rho/Rho-kinase can exactly activate. This review hence highlights the two questions after a profound survey of published literatures. Rho/Rho-kinase can exert positive feedback with just another kinase/signal transducers and activator of transcription, receptor tyrosine kinase signal pathways, even reactive oxygen species, which seem to comprise certain signal loops. The authors also presume, accordingly, that the positive feedback suggests a possible reason for exacerbation of some kind of inflammatory diseases including asthma, rheumatoid arthritis, multiple sclerosis, atherosclerosis, etc. This essay, therefore, provides a new angle of view for the therapy of these kinds of diseases.
1. Sibilano R, Frossi B, Suzuki R, D'Inca F, Gri G, Piconese S, et al. Modulation of FcepsilonRI-dependent mast cell response by OX40L via Fyn, PI3K, and RhoA. J Allergy Clin Immunol 2012; 130(3):751-60.
2. Sashio T, Kume H, Takeda N, Asano T, Tsuji S, Kondo M, et al. Possible Involvement of Sphingosine-1- Phosphate/G(i)/RhoA pathways in adherence of eosinophils to pulmonary endothelium. Allergol Int 2012; 61(2):283-93.
3. Jiang J, George SC. TGF-beta2 reduces nitric oxide synthase mRNA through a ROCK-dependent pathway in airway epithelial cells. Am J Physiol Lung Cell Mol Physiol 2011; 301(3):L361-7.
4. Lacy P, Willetts L, Kim JD, Lo AN, Lam B, Maclean EI, et al. Agonist activation of f-actin-mediated eosinophil shape change and mediator release is dependent on Rac2. Int Arch Allergy Immunol 2011;156(2):137-47.
5. Firouzi M, Sabouni F, Deezagi A, Pirbasti ZH, Poorrajab F, Rahimi-Movaghar V. Schwann cell apoptosis and p75(NTR) siRNA. Iran J Allergy Asthma Immunol 2011; 10(1):53-9.
6. Kume H. RhoA/Rho-kinase as a therapeutic target in asthma. Curr Med Chem 2008; 15(27):2876-85.
7. Sawada N, Liao JK. Rho/Rho-Associated Coiled-Coil Forming Kinase Pathway as Therapeutic Targets for Statins in Atherosclerosis. Antioxid Redox Signal 2013.
8. He Y, Xu H, Liang L, Zhan Z, Yang X, Yu X, et al.Antiinflammatory effect of Rho kinase blockade via inhibition of NF-kappaB activation in rheumatoid arthritis. Arthritis Rheum 2008; 58(11):3366-76.
9. Paintlia AS, Paintlia MK, Singh AK, Singh I. Inhibition of rho family functions by lovastatin promotes myelin repair in ameliorating experimental autoimmune encephalomyelitis. Mol Pharmacol 2008; 73(5):1381-93.
10. Sun X, Minohara M, Kikuchi H, Ishizu T, Tanaka M, Piao H, et al. The selective Rho-kinase inhibitor Fasudil is protective and therapeutic in experimental autoimmune encephalomyelitis. J Neuroimmunol 2006;180(1-2):126-34.
11. Kishore R, Qin G, Luedemann C, Bord E, Hanley A, Silver M, et al. The cytoskeletal protein ezrin regulates EC proliferation and angiogenesis via TNF-alpha- induced transcriptional repression of cyclin A. J Clin Invest 2005; 115(7):1785-96.
12. Shibuya M, Hirai S, Seto M, Satoh S, Ohtomo E.Effects of fasudil in acute ischemic stroke: results of a prospective placebo-controlled double-blind trial. J Neurol Sci 2005; 238(1-2):31-9.
13. Bivalacqua TJ, Champion HC, Usta MF, Cellek S, Chitaley K, Webb RC, et al. RhoA/Rho-kinase suppresses endothelial nitric oxide synthase in the penis: a mechanism for diabetes-associated erectile dysfunction. Proceedings of the National Academy of Sciences of the United States of America.2004;101(24):9121-6.
14. Uehata M, Ishizaki T, Satoh H, Ono T, Kawahara T, Morishita T, et al. Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension. Nature 1997; 389(6654):990-4.
15. Bao W, Hu E, Tao L, Boyce R, Mirabile R, Thudium DT, et al. Inhibition of Rho-kinase protects the heart against ischemia/reperfusion injury. Cardiovasc Res 2004; 61(3):548-58.
16. Sawada N, Itoh H, Miyashita K, Tsujimoto H, Sone M, Yamahara K, et al. Cyclic GMP kinase and RhoA Ser188 phosphorylation integrate pro- and antifibrotic signals in blood vessels. Mol Cell Biol 2009;29(22):6018-32.
17. Shimizu T, Fukumoto Y, Tanaka S, Satoh K, Ikeda S, Shimokawa H. Crucial Role of ROCK2 in Vascular Smooth Muscle Cells for Hypoxia-Induced Pulmonary Hypertension in Mice. Arterioscler Thromb Vasc Biol 2013; 33(12):2780-91.
18. Abe K, Shimokawa H, Morikawa K, Uwatoku T, Oi K, Matsumoto Y, et al. Long-term treatment with a Rho- kinase inhibitor improves monocrotaline-induced fatal pulmonary hypertension in rats. Circ Res 2004; 94(3):385-93.
19. Hattori T, Shimokawa H, Higashi M, Hiroki J, Mukai Y, Kaibuchi K, et al. Long-term treatment with a specific Rho-kinase inhibitor suppresses cardiac allograft vasculopathy in mice. Circ Res 2004;94(1):46-52.
20. Shimokawa H, Rashid M. Development of Rho-kinase inhibitors for cardiovascular medicine. Trends Pharmacol Sci 2007; 28(6):296-302.
21. Shimokawa H, Rashid M. Development of Rho-kinase inhibitors for cardiovascular medicine. Trends Pharmacol Sci 2007; 28(6):296-302.
22. Mueller BK, Mack H, Teusch N. Rho kinase, a promising drug target for neurological disorders. Nat Rev Drug Discov 2005; 4(5):387-98.
23. Somlyo AP, Somlyo AV. Signal transduction by G- proteins, rho-kinase and protein phosphatase to smooth muscle and non-muscle myosin II. J Physiol 2000; 522 Pt 2:177-85.
24. Delpuech O, Trabut JB, Carnot F, Feuillard J, Brechot C, Kremsdorf D. Identification, using cDNA macroarray analysis, of distinct gene expression profiles associated with pathological and virological features of hepatocellular carcinoma. Oncogene 2002; 21(18):2926-37.
25. Li XR, Ji F, Ouyang J, Wu W, Qian LY, Yang KY. Overexpression of RhoA is associated with poor prognosis in hepatocellular carcinoma. Eur J Surg
26. Wang D, Dou K, Xiang H, Song Z, Zhao Q, Chen Y, et al. Involvement of RhoA in progression of human hepatocellular carcinoma. J Gastroenterol Hepatol 2007; 22(11):1916-20.
27. Seabra MC. Membrane association and targeting of prenylated Ras-like GTPases. Cell Signal 1998;10(3):167-72.
28. Forget MA, Desrosiers RR, Gingras D, Beliveau R. Phosphorylation states of Cdc42 and RhoA regulate their interactions with Rho GDP dissociation inhibitor and their extraction from biological membranes. Biochem J 2002; 361(Pt 2):243-54.
29. Lang P, Gesbert F, Delespine-Carmagnat M, Stancou R, Pouchelet M, Bertoglio J. Protein kinase A phosphorylation of RhoA mediates the morphological and functional effects of cyclic AMP in cytotoxic lymphocytes. EMBO J 1996; 15(3):510-9.
30. Sawada N, Itoh H, Yamashita J, Doi K, Inoue M, Masatsugu K, et al. cGMP-dependent protein kinase phosphorylates and inactivates RhoA. Biochem Biophys Res Commun 2001; 280(3):798-805.
31. Ma X, Cheng Z, Kong H, Wang Y, Unruh H, Stephens NL, et al. Changes in biophysical and biochemical properties of single bronchial smooth muscle cells from asthmatic subjects. Am J Physiol Lung Cell Mol Physiol 2002; 283(6):L1181-9.
32. Janssen LJ, Tazzeo T, Zuo J, Pertens E, Keshavjee S. KCl evokes contraction of airway smooth muscle via activation of RhoA and Rho-kinase. Am J Physiol Lung Cell Mol Physiol 2004;287(4):L852-L8.
33. Taya S, Inagaki N, Sengiku H, Makino H, Iwamatsu A, Urakawa I, et al. Direct interaction of insulin-like growth factor-1 receptor with leukemia-associated RhoGEF. J Cell Biol 2001; 155(5):809-20.
34. Chiba Y, Nakazawa S, Todoroki M, Shinozaki K, Sakai H, Misawa M. Interleukin-13 augments bronchial smooth muscle contractility with an up-regulation of RhoA protein. Am J Respir Cell Mol Biol 2009; 40(2):159-67.
35. Goto K, Chiba Y, Matsusue K, Hattori Y, Maitani Y, Sakai H, et al. The proximal STAT6 and NF-kappaB sites are responsible for IL-13- and TNF-alpha-induced RhoA transcriptions in human bronchial smooth muscle cells. Pharmacol Res 2010; 61(5):466-72.
36. Leung T, Manser E, Tan L, Lim L. A novel serine/threonine kinase binding the Ras-related RhoA GTPase which translocates the kinase to peripheral membranes. J Biol Chem 1995; 270(49):29051-4.
37. Matsui T, Amano M, Yamamoto T, Chihara K, Nakafuku M, Ito M, et al. Rho-associated kinase, a novel serine/threonine kinase, as a putative target for small GTP binding protein Rho. EMBO J 1996; 15(9):2208-16.
38. Schaafsma D, Gosens R, Zaagsma J, Halayko AJ, Meurs H. Rho kinase inhibitors: a novel therapeutical intervention in asthma? Eur J Pharmacol 2008; 585(2-3):398-406.
39. Riento K, Ridley AJ. Rocks: multifunctional kinases in cell behaviour. Nat Rev Mol Cell Biol 2003; 4(6):446-56.
40. Rikitake Y, Liao JK. ROCKs as therapeutic targets in cardiovascular diseases. Expert Rev Cardiovasc Ther 2005; 3(3):441-51.
41. Kaibuchi K, Kuroda S, Amano M. Regulation of the cytoskeleton and cell adhesion by the Rho family GTPases in mammalian cells. Annu Rev Biochem 1999; 68:459-86.
42. Kjoller L, Hall A. Signaling to Rho GTPases. Exp CellRes 1999; 253(1):166-79.
43. Fukuhara S, Chikumi H, Gutkind JS. RGS-containingRhoGEFs: the missing link between transforming G proteins and Rho? Oncogene 2001; 20(13):1661-8.
44. Dutt P, Nguyen N, Toksoz D. Role of Lbc RhoGEF in Galpha12/13-induced signals to Rho GTPase. CellSignal 2004; 16(2):201-9.
45. Chikumi H, Barac A, Behbahani B, Gao Y, TeramotoH, Zheng Y, et al. Homo- and hetero-oligomerization of PDZ-RhoGEF, LARG and p115RhoGEF by their C- terminal region regulates their in vivo Rho GEF activity and transforming potential. Oncogene 2004; 23(1):233-40.
46. Ogita H, Kunimoto S, Kamioka Y, Sawa H, Masuda M, Mochizuki N. EphA4-mediated Rho activation via Vsm-RhoGEF expressed specifically in vascular smooth muscle cells. Circ Res 2003; 93(1):23-31.
47. Shamah SM, Lin MZ, Goldberg JL, Estrach S, Sahin M, Hu L, et al. EphA receptors regulate growth cone dynamics through the novel guanine nucleotide exchange factor ephexin. Cell 2001; 105(2):233-44.
48. Xie X, Chang SW, Tatsumoto T, Chan AM, Miki T. TIM, a Dbl-related protein, regulates cell shape and cytoskeletal organization in a Rho-dependent manner. Cell Signal 2005; 17(4):461-71.
49. Taggart MJ, Lee YH, Morgan KG. Cellular redistribution of PKCalpha, rhoA, and ROKalpha following smooth muscle agonist stimulation. Exp Cell Res 1999; 251(1):92-101.
50. Del Pozo MA, Kiosses WB, Alderson NB, Meller N, Hahn KM, Schwartz MA. Integrins regulate GTP-Rac localized effector interactions through dissociation ofRho-GDI. Nat Cell Biol 2002; 4(3):232-9.
51. Sanderson MJ, Delmotte P, Bai Y, Perez-Zogbhi JF. Regulation of airway smooth muscle cell contractility by Ca2+ signaling and sensitivity. Proc Am Thorac Soc2008; 5(1):23-31.
52. Casey PJ. Protein lipidation in cell signaling. Science1995; 268(5208):221-5.
53. Taggart MJ, Leavis P, Feron O, Morgan KG. Inhibition of PKCα and< i> rho</i> A Translocation in Differentiated Smooth Muscle by a Caveolin Scaffolding Domain Peptide. Exp Cell Res 2000; 258(1):72-81.
54. Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell 2009; 136(2):215-33.
55. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004; 116(2):281-97.
56. Ambros V. The functions of animal microRNAs. Nature 2004; 431(7006):350-5.
57. Care A, Catalucci D, Felicetti F, Bonci D, Addario A, Gallo P, et al. MicroRNA-133 controls cardiac hypertrophy. Nat Med 2007; 13(5):613-8.
58. Kong W, Yang H, He L, Zhao JJ, Coppola D, Dalton WS, et al. MicroRNA-155 is regulated by the transforming growth factor beta/Smad pathway and contributes to epithelial cell plasticity by targetingRhoA. Mol Cell Biol 2008; 28(22):6773-84.
59. Valastyan S, Chang A, Benaich N, Reinhardt F, Weinberg RA. Concurrent suppression of integrin alpha5, radixin, and RhoA phenocopies the effects of miR-31 on metastasis. Cancer Res 2010; 70(12):5147-54.
60. Kitazawa T, Eto M, Woodsome TP, Khalequzzaman M. Phosphorylation of the myosin phosphatase targeting subunit and CPI-17 during Ca2+ sensitization in rabbit smooth muscle. J Physiol 2003; 546(Pt 3):879-89.
61. Bhattacharyya R, Wedegaertner PB. Characterization of
G alpha 13-dependent plasma membrane recruitment of p115RhoGEF. Biochem J 2003; 371(Pt 3):709-20.
62. Meyer BH, Freuler F, Guerini D, Siehler S. Reversible translocation of p115-RhoGEF by G(12/13)-coupled receptors. J Cell Biochem 2008; 104(5):1660-70.
63. Grabocka E, Wedegaertner PB. Functional consequences of G alpha 13 mutations that disrupt interaction with p115RhoGEF. Oncogene 2005; 24(13):2155-65.
64. Kitazawa T, Masuo M, Somlyo AP. G protein-mediated inhibition of myosin light-chain phosphatase in vascular smooth muscle. Proc Natl Acad Sci U S A 1991; 88(20):9307-10.
65. Chikumi H, Vazquez-Prado J, Servitja JM, Miyazaki H, Gutkind JS. Potent activation of RhoA by Galpha q and Gq-coupled receptors. J Biol Chem 2002; 277(30):27130-4.}
66. Booden MA, Siderovski DP, Der CJ. Leukemia- associated Rho guanine nucleotide exchange factor promotes G alpha q-coupled activation of RhoA. Mol
67. Vogt S, Grosse R, Schultz G, Offermanns S. Receptor- dependent RhoA activation in G12/G13-deficient cells:genetic evidence for an involvement of Gq/G11. J Biol Chem 2003; 278(31):28743-9.
68. Lutz S, Freichel-Blomquist A, Yang Y, Rumenapp U, Jakobs KH, Schmidt M, et al. The guanine nucleotide exchange factor p63RhoGEF, a specific link between Gq/11-coupled receptor signaling and RhoA. J Biol Chem 2005; 280(12):11134-9.
69. Watterson KR, Ratz PH, Spiegel S. The role of sphingosine-1-phosphate in smooth muscle contraction. Cell Signal 2005; 17(3):289-98.
70. Brinkmann V, Baumruker T. Pulmonary and vascular pharmacology of sphingosine 1-phosphate. Curr Opin Pharmacol 2006; 6(3):244-50.
71. Makino Y, Kume H, Oguma T, Sugishita M, Shiraki A, Hasegawa Y, et al. Role of sphingosine-1-phosphate inbeta-adrenoceptor desensitization via Ca(2+) sensitization in airway smooth muscle. Allergol Int 2012; 61(2):311-22.
72. Chiba Y, Suzuki K, Uechi M, Kurihara E, Goto K, Sakai H, et al. Downregulation of sphingosine-1- phosphate receptors in bronchial smooth muscle of mouse experimental asthma. Pharmacol Res 2010; 62(4):357-63.
73. Li Z, Hannigan M, Mo Z, Liu B, Lu W, Wu Y, et al. Directional sensing requires G beta gamma-mediatedPAK1 and PIX alpha-dependent activation of Cdc42. Cell 2003; 114(2):215-27.
74. Welch HC, Coadwell WJ, Ellson CD, Ferguson GJ, Andrews SR, Erdjument-Bromage H, et al. P-Rex1, a PtdIns(3,4,5)P3- and Gbetagamma-regulated guanine- nucleotide exchange factor for Rac. Cell 2002;108(6):809-21.
75. Dong X, Mo Z, Bokoch G, Guo C, Li Z, Wu D. P-Rex1 is a primary Rac2 guanine nucleotide exchange factor in mouse neutrophils. Curr Biol 2005; 15(20):1874-9.
76. Shen X, Koga T, Park BC, SundarRaj N, Yue BY. Rho GTPase and cAMP/protein kinase A signaling mediates myocilin-induced alterations in cultured human trabecular meshwork cells. J Biol Chem 2008;283(1):603-12.
77. Lubomirov LT, Reimann K, Metzler D, Hasse V, Stehle R, Ito M, et al. Urocortin-induced decrease in Ca2+ sensitivity of contraction in mouse tail arteries is attributable to cAMP-dependent dephosphorylation of MYPT1 and activation of myosin light chain phosphatase. Circ Res 2006; 98(9):1159-67.
78. Chiba Y, Todoroki M, Nishida Y, Tanabe M, Misawa M. A novel STAT6 inhibitor AS1517499 ameliorates antigen-induced bronchial hypercontractility in mice. Am J Respir Cell Mol Biol 2009; 41(5):516-24.
79. Sahai E, Marshall CJ. Differing modes of tumour cell invasion have distinct requirements for Rho/ROCKsignalling and extracellular proteolysis. Nat Cell Biol 2003; 5(8):711-9.
80. Nakayama M, Amano M, Katsumi A, Kaneko T, Kawabata S, Takefuji M, et al. Rho-kinase and myosinII activities are required for cell type and environment specific migration. Genes to cells : devoted to molecular & cellular mechanisms 2005; 10(2):107-17.
81. Niggli V, Schmid M, Nievergelt A. Differential roles of Rho-kinase and myosin light chain kinase in regulating shape, adhesion, and migration of HT1080 fibrosarcoma cells. Biochem Biophys Res Commun 2006;343(2):602-8.
82. Muessel MJ, Scott KS, Friedl P, Bradding P, Wardlaw AJ. CCL11 and GM-CSF differentially use the Rho GTPase pathway to regulate motility of human eosinophils in a three-dimensional microenvironment. J Immunol 2008; 180(12):8354-60.
83. Sundaresan M, Yu ZX, Ferrans VJ, Irani K, Finkel T. Requirement for generation of H2O2 for platelet- derived growth factor signal transduction. Science 1995; 270(5234):296-9.
84. Bae YS, Kang SW, Seo MS, Baines IC, Tekle E, ChockPB, et al. Epidermal growth factor (EGF)-induced generation of hydrogen peroxide. Role in EGF receptor- mediated tyrosine phosphorylation. J Biol Chem 1997; 272(1):217-21.
85. Meng TC, Fukada T, Tonks NK. Reversible oxidation and inactivation of protein tyrosine phosphatases in vivo. Mol Cell 2002; 9(2):387-99.
86. Lander HM, Milbank AJ, Tauras JM, Hajjar DP, Hempstead BL, Schwartz GD, et al. Redox regulation of cell signalling. Nature 1996; 381(6581):380-1.
87. Lander HM, Ogiste JS, Pearce SF, Levi R, Novogrodsky A. Nitric oxide-stimulated guanine nucleotide exchange on p21ras. J Biol Chem 1995; 270(13):7017-20.
88. Heo J, Campbell SL. Mechanism of p21Ras S- nitrosylation and kinetics of nitric oxide-mediated guanine nucleotide exchange. Biochemistry 2004; 43(8):2314-22.
89. Sauzeau V, Le Jeune H, Cario-Toumaniantz C, Smolenski A, Lohmann SM, Bertoglio J, et al. CyclicGMP-dependent protein kinase signaling pathway inhibits RhoA-induced Ca2+ sensitization of contraction in vascular smooth muscle. J Biol Chem2000; 275(28):21722-9.
90. Heo J, Raines KW, Mocanu V, Campbell SL. Redox regulation of RhoA. Biochemistry 2006; 45(48):14481-9.
91. Heo J, Raines KW, Mocanu V, Campbell SL. Redox regulation of RhoA. Biochemistry 2006; 45(48):14481-9.
92. Aghajanian A, Wittchen ES, Campbell SL, Burridge K.Direct activation of RhoA by reactive oxygen species requires a redox-sensitive motif. PLoS One 2009;4(11):e8045.
93. Kawikova I, Barnes PJ, Takahashi T, Tadjkarimi S, Yacoub MH, Belvisi MG. 8-Epi-PGF2 alpha, a novel noncyclooxygenase-derived prostaglandin, constricts airways in vitro. Am J Respir Crit Care Med 1996;153(2):590-6.
94. Janssen LJ, Premji M, Netherton S, Catalli A, Cox G, Keshavjee S, et al. Excitatory and inhibitory actions of isoprostanes in human and canine airway smooth muscle. J Pharmacol Exp Ther 2000; 295(2):506-11.
95. Shiraki A, Kume H, Oguma T, Makino Y, Ito S,Shimokata K, et al. Role of Ca2+ mobilization and Ca2+ sensitization in 8-iso-PGF 2 alpha-induced contraction in airway smooth muscle. Clin Exp Allergy2009; 39(2):236-45.
96. Kojima K, Kume H, Ito S, Oguma T, Shiraki A, Kondo M, et al. Direct effects of hydrogen peroxide on airway smooth muscle tone: roles of Ca2+ influx and Rho- kinase. Eur J Pharmacol 2007; 556(1-3):151-6.
97. Schaafsma D, McNeill KD, Stelmack GL, Gosens R, Baarsma HA, Dekkers BG, et al. Insulin increases the expression of contractile phenotypic markers in airway smooth muscle. Am J Physiol Cell Physiol 2007;293(1):C429-39.
98. Dekkers BG, Schaafsma D, Tran T, Zaagsma J, Meurs H. Insulin-induced laminin expression promotes a hypercontractile airway smooth muscle phenotype. Am J Respir Cell Mol Biol 2009; 41(4):494-504.
99. Takaki H, Minoda Y, Koga K, Takaesu G, YoshimuraA, Kobayashi T. TGF-beta1 suppresses IFN-gamma- induced NO production in macrophages by suppressing STAT1 activation and accelerating iNOS protein degradation. Genes Cells 2006; 11(8):871-82.
100. Mitani T, Terashima M, Yoshimura H, Nariai Y, Tanigawa Y. TGF-beta1 enhances degradation of IFN- gamma-induced iNOS protein via proteasomes in RAW264.7 cells. Nitric Oxide 2005; 13(1):78-87.
101. Aikawa R, Komuro I, Yamazaki T, Zou Y, Kudoh S, Zhu W, et al. Rho family small G proteins play critical roles in mechanical stress-induced hypertrophic responses in cardiac myocytes. Circ Res 1999;84(4):458-66.
102. Yamazaki T, Komuro I, Kudoh S, Zou Y, Shiojima I, Mizuno T, et al. Mechanical stress activates protein kinase cascade of phosphorylation in neonatal rat cardiac myocytes. J Clin Invest 1995; 96(1):438-46.
103. Komuro I, Kaida T, Shibazaki Y, Kurabayashi M, Katoh Y, Hoh E, et al. Stretching cardiac myocytes stimulates protooncogene expression. J Biol Chem1990; 265(7):3595-8.
104. Kumar A, Knox AJ, Boriek AM. CCAAT/enhancer- binding protein and activator protein-1 transcription factors regulate the expression of interleukin-8 through the mitogen-activated protein kinase pathways in response to mechanical stretch of human airway smooth muscle cells. J Biol Chem 2003; 278(21):18868-76.
105. Mohamed JS, Boriek AM. Stretch augments TGF-beta1 expression through RhoA/ROCK1/2, PTK, and PI3K in airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 2010; 299(3):L413-24.
106. Mita M, Yanagihara H, Hishinuma S, Saito M, Walsh MP. Membrane depolarization-induced contraction of rat caudal arterial smooth muscle involves Rho- associated kinase. Biochem J 2002; 364(Pt 2):431-40.
107. Sakurada S, Takuwa N, Sugimoto N, Wang Y, Seto M, Sasaki Y, et al. Ca2+-dependent activation of Rho and Rho kinase in membrane depolarization-induced and receptor stimulation-induced vascular smooth muscle contraction. Circ Res 2003; 93(6):548-56.
108. Janssen LJ, Tazzeo T, Zuo J, Pertens E, Keshavjee S.KCl evokes contraction of airway smooth muscle via activation of RhoA and Rho-kinase. Am J Physiol Lung Cell Mol Physiol 2004; 287(4):L852-8.
109. Rikitake Y, Liao JK. Rho-kinase mediates hyperglycemia-induced plasminogen activator inhibitor-1 expression in vascular endothelial cells. Circulation 2005; 111(24):3261-8.
110. Hirose A, Tanikawa T, Mori H, Okada Y, Tanaka Y.Advanced glycation end products increase endothelial permeability through the RAGE/Rho signaling pathway. FEBS Lett 2010; 584(1):61-6.
111. Goldin A, Beckman JA, Schmidt AM, Creager MA.Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation 2006; 114(6):597-605.
112. Tang DD, Zhang W, Gunst SJ. The adapter protein CrkII regulates neuronal Wiskott-Aldrich syndrome protein, actin polymerization, and tension developmentduring contractile stimulation of smooth muscle. J Biol Chem 2005; 280(24):23380-9.
113. Schaafsma D, Roscioni SS, Meurs H, Schmidt M.Monomeric G-proteins as signal transducers in airway physiology and pathophysiology. Cell Signal 2008;20(10):1705-14.
114. Pelletier S, Duhamel F, Coulombe P, Popoff MR, Meloche S. Rho family GTPases are required for activation of Jak/STAT signaling by G protein-coupled receptors. Mol Cell Biol 2003; 23(4):1316-33.
115. Faruqi TR, Gomez D, Bustelo XR, Bar-Sagi D, Reich NC. Rac1 mediates STAT3 activation by autocrine IL-6. Proc Natl Acad Sci U S A 2001; 98(16):9014-9.
116. Simon AR, Vikis HG, Stewart S, Fanburg BL, Cochran BH, Guan KL. Regulation of STAT3 by direct binding to the Rac1 GTPase. Science 2000; 290(5489):144-7.
117. Shiga N, Hirano K, Hirano M, Nishimura J, Nawata H,Kanaide H. Long-term inhibition of RhoA attenuates vascular contractility by enhancing endothelial NO production in an intact rabbit mesenteric artery. Circ Res 2005; 96(9):1014-21.
118. Liao JK. Inhibition of Gi proteins by low density lipoprotein attenuates bradykinin-stimulated release of endothelial-derived nitric oxide. J Biol Chem 1994;269(17):12987-92.
119. Alderson LM, Endemann G, Lindsey S, Pronczuk A, Hoover R, Hayes K. LDL enhances monocyte adhesion to endothelial cells in vitro. Am J Pathol 1986;123(2):334-42.
120. Billington CK, Kong KC, Bhattacharyya R, Wedegaertner PB, Panettieri RA, Jr., Chan TO, et al. Cooperative regulation of p70S6 kinase by receptor tyrosine kinases and G protein-coupled receptors augments airway smooth muscle growth. Biochemistry 2005; 44(44):14595-605.
121. Kong KC, Billington CK, Gandhi U, Panettieri RA, Jr., Penn RB. Cooperative mitogenic signaling by G protein-coupled receptors and growth factors is dependent on G(q/11). FASEB J 2006; 20(9):1558-60.
122. Gosens R, Dueck G, Rector E, Nunes RO, Gerthoffer WT, Unruh H, et al. Cooperative regulation of GSK-3 by muscarinic and PDGF receptors is associated with airway myocyte proliferation. Am J Physiol Lung Cell Mol Physiol 2007; 293(5):L1348-58.
123. Farah S, Agazie Y, Ohan N, Ngsee JK, Liu XJ. A rho- associated protein kinase, ROKalpha, binds insulin receptor substrate-1 and modulates insulin signaling. J Biol Chem 1998; 273(8):4740-6.
124. Lim MJ, Choi KJ, Ding Y, Kim JH, Kim BS, Kim YH,et al. RhoA/Rho kinase blocks muscle differentiation via serine phosphorylation of insulin receptor substrate-1 and -2. Mol Endocrinol 2007; 21(9):2282-93.
125. Furukawa N, Ongusaha P, Jahng WJ, Araki K, Choi CS, Kim HJ, et al. Role of Rho-kinase in regulation of insulin action and glucose homeostasis. Cell Metab 2005; 2(2):119-29.
126. Kaneko T, Amano M, Maeda A, Goto H, Takahashi K, Ito M, et al. Identification of calponin as a novel substrate of Rho-kinase. Biochem Biophys Res Commun 2000; 273(1):110-6.
127. Charron F, Tsimiklis G, Arcand M, Robitaille L, Liang Q, Molkentin JD, et al. Tissue-specific GATA factors are transcriptional effectors of the small GTPase RhoA. Genes Dev 2001; 15(20):2702-19.
128. Yanazume T, Hasegawa K, Wada H, Morimoto T, Abe M, Kawamura T, et al. Rho/ROCK pathway contributes to the activation of extracellular signal-regulated kinase/GATA-4 during myocardial cell hypertrophy. J Biol Chem 2002; 277(10):8618-25.
129. Brown JH, Del Re DP, Sussman MA. The Rac and Rho hall of fame a decade of hypertrophic signaling hits. Circ Res 2006; 98(6):730-42.
130. Kuwahara K, Saito Y, Nakagawa O, Kishimoto I, Harada M, Ogawa E, et al. The effects of the selective ROCK inhibitor, Y27632, on ET-1-induced hypertrophic response in neonatal rat cardiac myocytes–possible involvement of Rho/ROCK pathway in cardiac muscle cell hypertrophy. FEBS letters 1999; 452(3):314-8.
131. Li X, Liu L, Tupper JC, Bannerman DD, Winn RK, Sebti SM, et al. Inhibition of protein geranylgeranylation and RhoA/RhoA kinase pathway induces apoptosis in human endothelial cells. J Biol Chem 2002; 277(18):15309-16.
132. De Sarno P, Shestopal SA, Zmijewska AA, Jope RS.Anti-apoptotic effects of muscarinic receptor activation are mediated by Rho kinase. Brain Res 2005;1041(1):112-5.
133. Moorman JP, Luu D, Wickham J, Bobak DA, Hahn CS.A balance of signaling by Rho family small GTPases RhoA, Rac1 and Cdc42 coordinates cytoskeletal morphology but not cell survival. Oncogene 1999;18(1):47-57.
134. Esteve P, Embade N, Perona R, Jimenez B, del Peso L, Leon J, et al. Rho-regulated signals induce apoptosis in vitro and in vivo by a p53-independent, but Bcl2 dependent pathway. Oncogene 1998; 17(14):1855-69.
135. Berestetskaya YV, Faure MP, Ichijo H, Voyno-Yasenetskaya TA. Regulation of apoptosis by alpha- subunits of G12 and G13 proteins via apoptosis signal- regulating kinase-1. J Biol Chem 1998; 273(43):27816-23.
136. Condorelli G, Morisco C, Stassi G, Notte A, Farina F, Sgaramella G, et al. Increased cardiomyocyte apoptosis and changes in proapoptotic and antiapoptotic genes bax and bcl-2 during left ventricular adaptations to chronic pressure overload in the rat. Circulation 1999;
99(23):3071-8.
137. Del Re DP, Miyamoto S, Brown JH. RhoA/Rho kinase up-regulate Bax to activate a mitochondrial death pathway and induce cardiomyocyte apoptosis. J Biol Chem 2007; 282(11):8069-78.
138. Uehata M, Ishizaki T, Satoh H, Ono T, Kawahara T,Morishita T, et al. Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension. Nature 1997; 89(6654):990-4.
139. Ishizaki T, Uehata M, Tamechika I, Keel J, Nonomura K, Maekawa M, et al. Pharmacological properties of Y-27632, a specific inhibitor of rho-associated kinases. Mol Pharmacol 2000; 57(5):976-83.
140. Sasaki Y, Suzuki M, Hidaka H. The novel and specific Rho-kinase inhibitor (S)-(+)-2-methyl-1-[(4-methyl-5- isoquinoline) sulfonyl]-homopiperazine as a probing molecule for Rho-kinase-involved pathway. Pharmacol Ther 2002; 93(2):225-32.
141. Hirooka Y, Shimokawa H. Therapeutic potential of rho- kinase inhibitors in cardiovascular diseases. Am J Cardiovasc Drugs 2005; 5(1):31-9.
142. Löhn M, Plettenburg O, Ivashchenko Y, Kannt A, Hofmeister A, Kadereit D, et al. Pharmacological characterization of SAR407899, a novel rho-kinase inhibitor. Hypertension 2009; 54(3):676-83.
143. Schaafsma D, Gosens R, Zaagsma J, Halayko AJ, Meurs H. Rho kinase inhibitors: a novel therapeutical intervention in asthma? Eur J Pharmacol 2008; 585(2-3):398-406.
144. Kast R, Schirok H, Figueroa-Pérez S, Mittendorf J, Gnoth MJ, Apeler H, et al. Cardiovascular effects of a novel potent and highly selective azaindole-based inhibitor of Rho-kinase. Br J Pharmacol 2007;152(7):1070-80.
145. Doe C, Bentley R, Behm DJ, Lafferty R, Stavenger R, Jung D, et al. Novel Rho kinase inhibitors with anti- inflammatory and vasodilatory activities. J Pharmacol Exp Ther 2007; 320(1):89-98.
146. Forstermann U, Munzel T. Endothelial nitric oxide synthase in vascular disease: from marvel to menace. Circulation 2006; 113(13):1708-14.
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Issue | Vol 13, No 6 (2014) | |
Section | Articles | |
Keywords | ||
Ca2 mobilization Ca2 sensitization Rho/Rho-kinase Signal pathway Positive feedback Signal loops |
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