Kinases as therapeutic targets for heart failure

Nature Reviews Drug Discovery

Volumn 2, Issue 2, 2003, Pages 99-113

  Vlahos, Chris J ^a   McDowell, Susan A ^a   Clerk, Angela ^b  

^a ELI LILLY AND COMPANY   (United States)

^b IMPERIAL COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

12 (2 CYANOETHYL) 6,7,12,13 TETRAHYDRO 13 METHYL 5 OXOINDOLO[2,3 A]PYRROLO[3,4 C]CARBAZOLE; 2 [1 (3 DIMETHYLAMINOPROPYL) 3 INDOLYL] 3 (3 INDOLYL)MALEIMIDE; 3 [8 [(DIMETHYLAMINO)METHYL] 6,7,8,9 TETRAHYDROPYRIDO[1,2 A]INDOL 10 YL] 4 (1 METHYL 1H INDOL 3 YL) 1H PYRROLE 2,5 DIONE; 4 (4 FLUOROPHENYL) 2 (4 HYDROXYPHENYL) 5 (4 PYRIDYL)IMIDAZOLE; 4 (4 FLUOROPHENYL) 2 (4 METHYLSULFINYLPHENYL) 5 (4 PYRIDYL)IMIDAZOLE; BETA ADRENERGIC RECEPTOR; BISINDOLYLMALEIMIDE; CALPHOSTIN C; CHELERYTHRINE; JANUS KINASE; LY 379196; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE INHIBITOR; MITOGEN ACTIVATED PROTEIN KINASE KINASE; PHOSPHATIDYLINOSITOL 3 KINASE; POLYMYXIN B; PROTEIN KINASE; PROTEIN KINASE C INHIBITOR; ROTTLERIN; RUBOXISTAURIN; STAUROSPORINE; SYNAPTOPHYSIN; ENZYME INHIBITOR; ISOENZYME; MITOGEN ACTIVATED PROTEIN KINASE; PHOSPHOTRANSFERASE; PROTEIN KINASE C;

ANTIINFLAMMATORY ACTIVITY; DRUG MARKETING; DRUG MECHANISM; DRUG TARGETING; ENZYME ACTIVATION; ENZYME INHIBITION; HEART FAILURE; HUMAN; NONHUMAN; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; REVIEW; SIGNAL TRANSDUCTION; STRUCTURE ACTIVITY RELATION; ANIMAL; CONGESTIVE HEART FAILURE; DRUG ANTAGONISM; ENZYMOLOGY; HEART MUSCLE; METABOLISM; PHYSIOLOGY;

1-PHOSPHATIDYLINOSITOL 3-KINASE; ANIMALS; ENZYME INHIBITORS; HEART FAILURE, CONGESTIVE; HUMANS; ISOENZYMES; MITOGEN-ACTIVATED PROTEIN KINASES; MYOCARDIUM; PHOSPHOTRANSFERASES; PROTEIN KINASE C;

EID: 0037315861     PISSN: 14741776     EISSN: None     Source Type: Journal    
DOI: 10.1038/nrd1009     Document Type: Review

References (160)

1. Mackay, K. & Mochly-Rosen, D. Localization, anchoring, and functions of protein kinase C isozymes in the heart. J. Mol. Cell. Cardiol. 33, 1301-1307 (2001).
2. Shin, H. G. et al. Molecular heterogeneity of protein kinase C expression in human ventricle. Cardiovasc. Res. 48, 285-299 (2000).
3. Shubeita, H. E., Martinson, E. A., Van Bilsen, M., Chien, K. R. & Brown, J. H. Transcriptional activation of the cardiac myosin light chain 2 and atrial natriuretic factor genes by protein kinase C in neonatal rat ventricular myocytes. Proc. Natl Acad. Sci. USA 89, 1305-1309 (1992).
4. Kariya, K., Karns, L. R. & Simpson, P. C. An enhancer core element mediates stimulation of the rat β-myosin heavy chain promoter by an α1-adrenergic agonist and activated β-protein kinase C in hypertrophy of cardiac myocytes. J. Biol. Chem. 269, 3775-3782 (1994).
5. Sadoshima, J. & Izumo, S. Mechanical stretch rapidly activates multiple signal transduction pathways in cardiac myocytes: potential involvement of an autocrine/paracrine mechanism. EMBO J. 12, 1681-1692 (1993).
6. Jiang, T., Pak, E., Zhang, H. L., Kline, R. P. & Steinberg, S. F. Endothelin-dependent actions in cultured AT-1 cardiac myocytes. The role of the E isoform of protein kinase C. Circ. Res. 78, 724-736 (1996).
7. Simpson, P. C., Long, C. S., Waspe, L. E., Henrich, C. J. & Ordahl, C. P. Transcription of early developmental isogenes in cardiac myocyte hypertrophy. J. Mol. Cell. Cardiol. 21, (Suppl 5) 79-89 (1989).
8. Goldberg, M. & Steinberg, S. F. Tissue-specific developmental regulation of protein kinase C isoforms. Biochem. Pharmacol. 51, 1089-1093 (1996).
9. Inoguchi, T. et al. Preferential elevation of protein kinase C isoform βII and diacylglycerol levels in the aorta and heart of diabetic rats: differential reversibility to glycemic control by islet cell transplantation. Proc. Natl Acad. Sci. USA 89, 11059-11063 (1992).
10. Liu, X. et al. Changes in cardiac protein kinase C activities and isozymes in streptozotocin-induced diabetes. Am. J. Physiol. 277, E798-804 (1999).
11. Simonis, G., Honold, J., Schwarz, K., Braun, M. U. & Strasser, R. H. Regulation of the isozymes of protein kinase C in the surviving rat myocardium after myocardial infarction: distinct modulation for PKC-α and for PKC-δ. Basic. Res. Cardiol. 97, 223-231 (2002).
12. 2+-sensitive isoforms in the failing human heart. Circulation 99, 384-391 (1999).
13. Disatnik, M. H., Buraggi, G. & Mochly-Rosen, D. Localization of protein kinase C isozymes in cardiac myocytes. Exp. Cell. Res. 210, 287-297 (1994).
14. Ron, D. et al. Cloning of an intracellular receptor for protein kinase C: a homolog of the β subunit of G proteins. Proc. Natl Acad. Sci. USA 91, 839-843 (1994).
15. Rodriguez, M. M., Ron, D., Touhara, K., Chen, C. H. & Mochly-Rosen, D. RACK1, a protein kinase C anchoring protein, coordinates the binding of activated protein kinase C and select pleckstrin homology domains in vitro. Biochemistry 38, 13787-13794 (1999).
16. Johnson, J. A., Gray, M. O., Chen, C. H. & Mochly-Rosen, D. A protein kinase C translocation inhibitor as an isozyme-selective antagonist of cardiac function. J. Biol. Chem. 271, 24962-24966 (1996).
17. Gray, M. O., Karliner, J. S. & Mochly-Rosen, D. A selective E-protein kinase C antagonist inhibits protection of cardiac myocytes from hypoxia-induced cell death. J. Biol. Chem. 272, 30945-30951 (1997).
18. Ron, D., Luo, J. & Mochly-Rosen, D. C2 region-derived peptides inhibit translocation and function of β protein kinase C in vivo. J. Biol. Chem. 270, 24180-24187 (1995).
19. Ron, D. & Mochly-Rosen, D. An autoregulatory region in protein kinase C: the pseudoanchoring site. Proc. Natl Acad. Sci. USA 92, 492-496 (1995).
20. Braz, J. C., Bueno, O. F., De Windt, L. J. & Molkentin, J. D. PKC α regulates the hypertrophic growth of cardiomyocytes through extracellular signal-regulated kinase 1/2 (ERK1/2). J. Cell Biol. 156, 905-919 (2002).
21. Pecherskaya, A. & Solem, M. IGF1 activates PKC α-dependent protein synthesis in adult rat cardiomyocytes. Mol. Cell. Biol. Res Commun 4, 166-171 (2000).
22. Schafer, M. et al. β-adrenoceptor stimulation attenuates the hypertrophic effect of α-adrenoceptor stimulation in adult rat ventricular cardiomyocytes. J. Am. Coll. Cardiol. 37, 300-307 (2001).
23. Rohde, S., Sabri, A., Kamasamudran, R. & Steinberg, S. F. The α(1)-adrenoceptor subtype- and protein kinase C isoform-dependence of norepinephrine's actions in cardiomyocytes. J. Mol. Cell. Cardiol. 32, 1193-1209 (2000).
24. Dorn, G. W., 2nd, Tepe, N. M., Wu, G., Yatani, A. & Liggett, S. B. Mechanisms of impaired β-adrenergic receptor signaling in G(αq)- mediated cardiac hypertrophy and ventricular dysfunction. Mol. Pharmacol. 57, 278-287 (2000).
25. 2+-dependent transgenic model of cardiac hypertrophy: A role for protein kinase Cα. Circulation 103, 140-147 (2001).
26. Braun, M. U., LaRosee, P., Schon, S., Borst, M. M. & Strasser, R. H. Differential regulation of cardiac protein kinase C isozyme expression after aortic banding in rat. Cardiovasc. Res. 56, 52-63 (2002).
27. Takeishi, Y. et al. Effect of angiotensin-converting enzyme inhibition on protein kinase C and SR proteins in heart failure. Am. J. Physiol. 276, H53-62 (1999).
28. Wakasaki, H. et al. Targeted overexpression of protein kinase Cβ2 isoform in myocardium causes cardiomyopathy. Proc. Natl Acad. Sci. USA 94, 9320-9325 (1997).
29. Bowman, J. C. et al. Expression of protein kinase C β in the heart causes hypertrophy in adult mice and sudden death in neonates. J. Clin. Invest. 100, 2189-2195 (1997).
30. McDonald, T. F., Pelzer, S., Trautwein, W. & Pelzer, D. J. Regulation and modulation of calcium channels in cardiac, skeletal, and smooth muscle cells. Physiol. Rev. 74, 365-507 (1994).
31. 2+ channel and its modulation by protein kinase C. J. Biol. Chem. 273, 17901-17909 (1998).
32. 2+- and protein kinase C-dependent mechanism. Am. J. Physiol. Heart Circ. Physiol. 280, H1528-1536 (2001).
33. 2+ current from neonatal mouse ventricular myocytes by constitutively active PKC-βII. Am. J. Physiol. Cell. Physiol. 282, C768-774 (2002).
34. 2+ channels. Circ. Res. 80, 720-729 (1997).
35. Kazanietz, M. G. Novel 'nonkinase' phorbol ester receptors: the C1 domain connection. Mol. Pharmacol. 61, 759-767 (2002).
36. Qiu, Y. et al. Direct evidence that protein kinase C plays an essential role in the development of late preconditioning against myocardial stunning in conscious rabbits and that E is the isoform involved. J. Clin. Invest. 101, 2182-2198 (1998).
37. Takeishi, Y. et al. Transgenic overexpression of constitutively active protein kinase CE causes concentric cardiac hypertrophy. Circ. Res. 86, 1218-1223 (2000).
38. Mochly-Rosen, D. et al. Cardiotrophic effects of protein kinase CE: analysis by in vivo modulation of PKCE, translocation. Circ. Res. 86, 1173-1179 (2000).
39. Cross, H. R., Murphy, E., Bolli, R., Ping, P. & Steenbergen, C. Expression of activated PKC epsilon (PKCE) protects the ischemic heart, without attenuating ischemic H(+) production. J. Mol. Cell. Cardiol. 34, 361-367 (2002).
40. Chen, L. et al. Molecular transporters for peptides: delivery of a cardioprotective EPKC agonist peptide into cells and intact ischemic heart using a transport system, R(7). Chem. Biol. 8, 1123-1129 (2001).
41. Dorn, G. W. et al. Sustained in vivo cardiac protection by a rationally designed peptide that causes E protein kinase C translocation. Proc. Natl Acad. Sci. USA 96, 12798-12803 (1999).
42. Strait, J. B. et al. Role of protein kinase C-E in hypertrophy of cultured neonatal rat ventricular myocytes. Am. J. Physiol. Heart Circ. Physiol. 280, H756-766 (2001).
43. Gu, X. & Bishop, S. P. Increased protein kinase C and isozyme redistribution in pressure-overload cardiac hypertrophy in the rat. Circ. Pes. 75, 926-931 (1994).
44. D'Angelo, D. D. et al. Transgenic Gαq overexpression induces cardiac contractile failure in mice. Proc. Natl Acad. Sci. USA 94, 8121-8126 (1997).
45. Pass, J. M. et al. PKCE activation induces dichotomous cardiac phenotypes and modulates PKCE-RACK interactions and RACK expression. Am. J. Physiol. Heart Circ. Physiol. 280, H946-955 (2001).
46. Pass, J. M. et al. Enhanced PKC βII translocation and PKC βII-RACK1 interactions in PKC E-induced heart failure: a role for RACK1. Am. J. Physiol. Heart Circ. Physiol. 281, H2500-2510 (2001).
47. Chen, L. et al. Opposing cardioprotective actions and parallel hypertrophic effects of δPKC and EPKC. Proc. Natl Acad. Sci. USA 98, 11114-11119 (2001).
48. Shizukuda, Y., Reyland, M. E. & Buttrick, P. M. Protein kinase C-δ modulates apoptosis induced by hyperglycemia in adult ventricular myocytes. Am. J. Physiol. Heart Circ. Physiol. 282, H1625-1634 (2002).
49. Heidkamp, M. C., Bayer, A. L., Martin, J. L. & Samarel, A. M. Differential activation of mitogen-activated protein kinase cascades and apoptosis by protein kinase C E and δ in neonatal rat ventricular myocytes. Circ. Res. 89, 882-890 (2001).
50. Davies, S. P., Reddy, H., Caivano, M. & Cohen, P. Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem. J. 351, 95-105 (2000).
51. Clerk, A. Death by protein kinase C inhibitor: a stressful event. J. Mol. Cell. Cardiol. 33, 1773-1776 (2001).
52. Takeishi, Y. et al. In vivo phosphorylation of cardiac troponin I by protein kinase Cβ2 decreases cardiomyocyte calcium responsiveness and contractility in transgenic mouse hearts. J. Clin. Invest. 102, 72-78 (1998).
53. Way, K. J. et al. Expression of connective tissue growth factor is increased in injured myocardium associated with protein kinase C β2 activation and diabetes. Diabetes 51, 2709-2718 (2002).
54. Cantley L. C. The phosphoinositide 3-kinase pathway. Science 296, 1655-1657 (2002)
55. Vanhaesebroeck, B. et al. Synthesis and function of 3-phosphorylated inositol lipids. Annu. Rev. Biochem. 70, 535-602 (2001).
56. Schluter, K. D., Simm, A., Schafer, M., Taimor, G. & Piper, H. M. Early response kinase and PI 3-kinase activation in adult cardiomyocytes and their role in hypertrophy. Am. J. Physiol. 276, H1655-1663 (1999).
57. Pham, F. H., Sugden, P. H. & Clerk, A. Regulation of protein kinase B and 4E-BP1 by oxidative stress in cardiac myocytes. Circ. Res. 86, 1252-1258 (2000).
58. Morisco, C. et al. The Akt-glycogen synthase kinase 3β pathway regulates transcription of atrial natriuretic factor induced by β-adrenergic receptor stimulation in cardiac myocytes. J. Biol. Chem. 275, 14466-14475 (2000).
59. Haq, S. et al. Glycogen synthase kinase-3β is a negative regulator of cardiomyocyte hypertrophy. J. Cell Biol. 151, 117-130 (2000).
60. Schwartzbauer, G. & Robbins, J. The tumor suppressor gene PTEN can regulate cardiac hypertrophy and survival. J. Biol. Chem. 276, 35786-35793 (2001).
61. Crackower, M. et al. Regulation of myocardial contractility and cell size by distinct PI3K-PTEN signaling pathways. Cell 110, 737 (2002).
62. Shioi, T. et al. The conserved phosphoinositide 3-kinase pathway determines heart size in mice. EMBO J. 19, 2537-2548 (2000).
63. Shioi, T. et al. Akt/protein kinase B promotes organ growth in transgenic mice. Mol. Cell. Biol. 22, 2799-2809 (2002).
64. Matsui, T. et al. Phenotypic spectrum caused by transgenic overexpression of activated Akt in the heart. J. Biol. Chem. 277, 22896-22901 (2002).
65. Matsui, T. et al. Akt activation preserves cardiac function and prevents injury after transient cardiac ischemia in vivo. Circulation 104, 330-335 (2001).
66. Naga Prasad, S. V., Esposito, G., Mao, L., Koch, W. J. & Rockman, H. A. Gbetagamma-dependent phosphoinositide 3-kinase activation in hearts with in vivo pressure overload hypertrophy. J. Biol. Chem. 275, 4693-4698 (2000).
67. Esposito, G. et al. Genetic alterations that inhibit in vivo pressure-overload hypertrophy prevent cardiac dysfunction despite increased wall stress. Circulation 105, 85-92 (2002).
68. Haq, S. et al. Differential activation of signal transduction pathways in human hearts with hypertrophy versus advanced heart failure. Circulation 103, 670-677 (2001).
69. s signaling during β2-adrenergic stimulation. Circ. Res. 91, 46-53 (2002).
70. Rockman, H. A. et al. Expression of a beta-adrenergic receptor kinase 1 inhibitor prevents the development of myocardial failure in gene-targeted mice. Proc. Natl Acad. Sci. USA 95, 7000-7005 (1998).
71. Rockman, H. A, et al. Control of myocardial contractile function by the level of beta- adrenergic receptor kinase 1 in gene-targeted mice. J. Biol. Chem. 273, 18180-18184 (1998).
72. Harding, V. B., Jones, L. R., Lefkowitz, R. J., Koch, W. J. & Rockman, H. A. Cardiac βARK1 inhibition prolongs survival and augments beta clocker therapy in a mouse model of severe heart failure. Proc. Natl Acad. Sci. USA 98, 5809-5814 (2001).
73. 2+ spiking. Mol. Biol. Cell 11, 1845-1858 (2000).
74. 2+ oscillations in cardiac cells. J. Cell Biol. 152, 717-728 (2001).
75. 2+ channels. Br. J. Pharmacol. 132, 669-676 (2001).
76. Quignard, J. F. et al. Phosphoinositide 3-kinase γ mediates angiotensin II-induced stimulation of L-type calcium channels in vascular myocytes. J. Biol. Chem. 276, 32545-32551 (2001).
77. 2+ channels. Circ. Res. 89, 692-699 (2001).
78. 2+ release in cardiomyocytes. Nature Cell Biol. 3, 867-873 (2001).
79. Condorelli, G. et al. Akt induces enhanced myocardial contractility and cell size in vivo in transgenic mice. Proc. Natl Acad. Sci. USA 99, 12333-12338 (2002).
80. Blair, L. A. et al. Akt-dependent potentiation of L channels by insulin-like growth factor-1 is required for neuronal survival. J. Neurosci. 19, 1940-1951 (1999).
81. Fleckenstein, A. History of calcium antagonists. Circ. Res. 52, 13-16 (1983).
82. 2+ channels via phosphoinositide 3-kinase. FASEB J. 13, 685-694 (1999).
83. Wu, W et al. Expression of constitutively active phosphatidylinositol 3-kinase inhibits activation of caspase 3 and apoptosis of cardiac muscle cells. J. Biol. Chem. 275, 40113-40119 (2000).
84. Jonassen, A. K., Sack, M. N., Mjos, O. D. & Yellon, D. M. Myocardial protection by insulin at reperfusion requires early administration and is mediated via Akt and p70s6 kinase cell-survival signaling. Circ. Res. 89, 1191-1198 (2001).
85. Aikawa, R. et al. Insulin prevents cardiomyocytes from oxidative stress-induced apoptosis through activation of PI3 kinase/Akt. Circulation 102, 2873-2879 (2000).
86. Chesley, A. et al. The β(2)-adrenergic receptor delivers an antiapoptotic signal to cardiac myocytes through G(i)-dependent coupling to phosphatidylinositol 3′-kinase, Circ. Res. 87, 1172-1179 (2000).
87. Zhu, W. Z. et al. Dual modulation of cell survival and cell death by β2-adrenergic signaling in adult mouse cardiac myocytes. Proc. Natl Acad. Sci. USA 98, 1607-1612 (2001).
88. Valks, D. M. et al. Phenylephrine promotes phosphorylation of Bad in cardiac myocytes through the extracellular signal-regulated kinases 1/2 and protein kinase A. J. Mol. Cell. Cardiol. 34, 749-763 (2002).
89. Matsui, T. et al. Adenoviral gene transfer of activated phosphatidylinositol 3′-kinase and Akt inhibits apoptosis of hypoxic cardiomyocytes in vitro. Circulation 100, 2373-2379 (1999).
90. Fujio, Y., Nguyen, T., Wencker, D., Kitsis, R. N. & Walsh, K. Akt promotes survival of cardiomyocytes in vitro and protects against ischemia-reperfusion injury in mouse heart. Circulation 101, 660-667 (2000).
91. Brunet, A. et al. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 96, 857-868 (1999).
92. Mockridge, J. W., Marber, M. S. & Heads, R. J. Activation of Akt during simulated ischemia/reperfusion in cardiac myocytes. Biochem. Biophys. Res. Commun. 270, 947-952 (2000).
93. Tong, H., Chen, W., Steenbergen, C. & Murphy, E. Ischemic preconditioning activates phosphatidylinositol-3-kinase upstream of protein kinase C. Circ. Res. 87, 309-315 (2000).
94. Tong, H., Imahashi, K., Steenbergen, C. & Murphy, E. Phosphorylation of glycogen synthase kinase-3β during preconditioning through a phosphatidylinositol-3-kinase-dependent pathway is cardioprotective. Circ. Res. 90, 377-379 (2002).
95. Camper-Kirby, D. et al. Myocardial Akt activation and gender: increased nuclear activity in females versus males. Circ. Res. 88, 1020-1027 (2001).
96. Naccache, P. H. et al. Stimulation of human neutrophils by chemotactic factors is associated with the activation of phosphatidylinositol 3-kinase γ. J. Biol. Chem. 275, 23636-23641 (2000).
97. Kolch, W. Meaningful relationships: the regulation of the Ras/Raf/MEK/ERK pathway by protein interactions. Biochem. J. 351, 289-305 (2000).
98. Kyriakis, J. M. & Avruch, J. Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol. Rev. 81, 807-869 (2001).
99. Whitmarsh, A. J., Cavanagh, J., Tournier, C., Yasuda, J. & Davis, R. J. A mammalian scaffold complex that selectively mediates MAP kinase activation. Science 281, 1671-1674 (1998).
100. Zhou, G., Bao, Z. Q. & Dixon, J. E. Components of a new human protein kinase signal transduction pathway. J. Biol. Chem. 270, 12665-12669 (1995).
101. Davis, R. J. Signal transduction by the JNK group of MAP kinases. Cell 103, 239-252 (2000).
102. Sugden, P. H. & Clerk, A. Cellular mechanisms of cardiac hypertrophy. J. Mol. Med. 76, 725-746 (1998).
103. Dudley, D. T., Pang, L., Decker, S. J., Bridges, A. J. & Saltiel, A. R. A synthetic inhibitor of the mitogen-activated protein kinase cascade. Proc. Natl Acad. Sci. USA 92, 7686-7689 (1995).
104. Favata, M. F. et al. Identification of a novel inhibitor of mitagen-activated protein kinase kinase. J. Biol. Chem. 273, 18623-18632 (1998).
105. Clerk, A., Michael, A. & Sugden, P. H. Stimulation of the p38 mitogen-activated protein kinase pathway in neonatal rat ventricular myocytes by the G protein-coupled receptor agonists, endothelin-1 and phenylephrine: a role in cardiac myocyte hypertrophy? J. Cell Biol. 142, 523-535 (1998).
106. Hines, W. A. & Thorburn, A. Ras and rho are required for Gαq-induced hypertrophic gene expression in neonatal rat cardiac myocytes. J. Mol. Cell. Cardiol. 30, 485-494 (1998).
107. Aikawa, R. et al. Oxidative stress activates extracellular signal-regulated kinases through Src and Ras in cultured cardiac myocytes of neonatal rats. J. Clin. Invest. 100, 1813-1821 (1997).
108. Yue, T. L. et al. Inhibition of extracellular signal-regulated kinase enhances ischemia/reoxygenation-induced apoptosis in cultured cardiac myocytes and exaggerates reperfusion injury in isolated perfused heart. Circ. Res. 86, 692-699 (2000).
109. Alessi, D. R., Cuenda, A., Cohen, P., Dudley, D. T. & Saltiel, A. R. PD 098059 is a specific inhibitor of the activation of mitogen-activated protein kinase kinase in vitro and in vivo. J. Biol. Chem. 270, 27489-27494 (1995).
110. Yue, T. L. et al. Extracellular signal-regulated kinase plays an essential role in hypertrophic agonists, endothelin-1 and phenylephrine-induced cardiomyocyte hypertrophy. J. Biol. Chem. 275, 37895-37901 (2000).
111. Babu, G. J., Lalli, M. J., Sussman, M. A., Sadoshima, J. & Periasamy, M. Phosphorylation of elk-1 by MEK/ERK pathway is necessary for c-fos gene activation during cardiac myocyte hypertrophy. J. Mol. Cell. Cardiol. 32, 1447-1457 (2000).
112. Liang, Q. et al. The transcription factor GATA4 is activated by extracellular signal-regulated kinase 1- and 2-mediated phosphorylation of serine 105 in cardiomyocytes. Mol. Cell. Biol. 21, 7460-7469 (2001).
113. Bueno, O. F. et al. The MEK1-ERK1/2 signaling pathway promotes compensated cardiac hypertrophy in transgenic mice. EMBO J. 19, 6341-6350 (2000).
114. Chiloeches, A. et al. Regulation of Ras. GTP loading and Ras-Raf association in neonatal rat ventricular myocytes by G protein-coupled receptor agonists and phorbol ester. Activation of the extracellular signal-regulated kinase cascade by phorbol ester is mediated by Ras. J. Biol. Chem. 274, 19762-19770 (1999).
115. Mason, C. S. et al. Serine and tyrosine phosphorylations cooperate in Raf-1, but not B-Raf activation. EMBO J. 18, 2137-2148 (1999).
116. Dumaz, N., Light, Y. & Marais, R. Cyclic AMP blocks cell growth through Raf-1-dependent and Raf-1-independent mechanisms. Mol. Cell. Biol. 22, 3717-3728 (2002).
117. Zimmermann, S. & Moelling, K. Phosphorylation and regulation of Raf by Akt (protein kinase B). Science 286, 1741-1744 (1999).
118. Clerk, A. et al. Regulation of mitogen-activated protein kinases in cardiac myocytes through the small G protein Rac1. Mol. Cell. Biol. 21, 1173-1184 (2001).
119. Clerk, A., Gillespie-Brown, J., Fuller, S. J. & Sugden, P. H. Stimulation of phosphatidylinositol hydrolysis, protein kinase C translocation, and mitogen-activated protein kinase activity by bradykinin in rat ventricular myocytes: dissociation from the hypertrophic response. Biochem. J. 317, 109-118 (1996).
120. Camps, M., Nichols, A. & Arkinstall, S. Dual specificity phosphatases: a gene family for control of MAP kinase function. FASEB J. 14, 6-16 (2000).
121. El Oakley, R. M., Ooi, O. C., Bongso, A. & Yacoub, M. H. Myocyte transplantation for myocardial repair: a few good cells can mend a broken heart. Ann. Thorac. Surg. 71, 1724-1733 (2001).
122. Vaudry, D., Stork, P. J., Lazarovici, P. & Eiden, L. E. Signaling pathways for PC12 cell differentiation: making the right connections. Science 296, 1648-1649 (2002).
123. Sugden, P. H. & Clerk, A. 'Stress-responsive' mitogen-activated protein kinases (c-Jun N-terminal kinases and p38 mitogen-activated protein kinases) in the myocardium. Circ. Res. 83, 345-352 (1998)
124. Clerk, A., Harrison, J. G., Long, C. S. & Sugden, P. H. Pro-inflammatory cytokines stimulate mitogen-activated protein kinase subfamilies, increase phosphorylation of c-Jun and ATF2 and upregulate c-Jun protein in neonatal rat ventricular myocytes. J. Mol. Cell. Cardiol. 31, 2087-2099 (1999).
125. Bogoyevitch, M. A. et al. Stimulation of the stress-activated mitogen-activated protein kinase subfamilies in perfused heart. p38/RK mitogen-activated protein kinases and c-Jun N-terminal kinases are activated by ischemia/reperfusion. Circ. Res. 79, 162-173 (1996).
126. Lazou, A., Sugden, P. H. & Clerk, A. Activation of mitogen-activated protein kinases (p38-MAPKs, SAPKs/JNKs and ERKs) by the G-protein-coupled receptor agonist phenylephrine in the perfused rat heart. Biochem. J. 332, 459-465 (1998).
127. Cook, S. A., Sugden, P. H. & Clerk, A. Activation of c-Jun N-terminal kinases and p38-mitogen-activated protein kinases in human heart failure secondary to ischaemic heart disease. J. Mol. Cell. Cardiol. 31, 1429-1434 (1999).
128. Communal, C. et al. Reciprocal modulation of mitogen-activated protein kinases and mitogen-activated protein kinase phosphatase 1 and 2 in failing human myocardium. J. Card. Fail. 8, 86-92 (2002).
129. Lemke, L. E. et al. Decreased p38 MAPK activity in end-stage failing human myocardium: p38 MAPKα is the predominant isoform expressed in human heart. J. Mol. Cell. Cardiol. 33, 1527-1540 (2001).
130. Wang, Y. et al. Cardiac muscle cell hypertrophy and apoptosis induced by distinct members of the p38 mitogen-activated protein kinase family. J. Biol. Chem. 273, 2161-2168 (1998).
131. Aoki, H. et al. Direct activation of mitochondrial apoptosis machinery by c-Jun N-terminal kinase in adult cardiac myocytes. J. Biol. Chem. 277, 10244-10250 (2002).
132. Andreka, P. et al. Cytoprotection by Jun kinase during nitric oxide-induced cardiac myocyte apoptosis. Circ. Res. 88, 305-312 (2001).
133. Dougherty, C. J. et al. Activation of c-Jun N-terminal kinase promotes survival of cardiac myocytes after oxidative stress. Biochem. J. 362, 561-571 (2002).
134. Sadoshima, J. et al. The MEKK1-JNK pathway plays a protective role in pressure overload but does not mediate cardiac hypertrophy. J. Clin. Invest. 110, 271-279 (2002).
135. Liao, P. et al. The in vivo role of p38 MAP kinases in cardiac remodeling and restrictive cardiomyopathy. Proc. Natl Acad. Sci. USA 98, 12283-12288 (2001).
136. Clerk, A. & Sugden, P. H. The p38-MAPK inhibitor, SB203580, inhibits cardiac stress-activated protein kinases/c-Jun N-terminal kinases (SAPKs/JNKs). FEBS Lett. 426, 93-96 (1998).
137. Minamino, T. et al. MEKK1 is essential for cardiac hypertrophy and dysfunction induced by Gq. Proc. Natl Acad. Sci. USA 99, 3866-3871 (2002).
138. Zhang, D. et al. TAK1 is activated in the myocardium after pressure overload and is sufficient to provoke heart failure in transgenic mice. Nature Med. 6, 556-563 (2000).
139. Coso, O. A. et al. The small GTP-binding proteins Rac1 and Cdc42 regulate the activity of the JNK/SAPK signaling pathway. Cell 81, 1137-1146 (1995).
140. Lee, J. C. et al. Inhibition of p38 MAP kinase as a therapeutic strategy. Immunopharmacology 47, 185-201 (2000).
141. Clerk, A., Michael, A. & Sugden, P. H. Stimulation of multiple mitogen-activated protein kinase sub-families by oxidative stress and phosphorylation of the small heat shock protein, HSP25/27, in neonatal ventricular myocytes. Biochem. J. 333, 581-589 (1998).
142. Huot, J. et al. Characterization of 45-kDa/54-kDa HSP27 knase, a stress-sensitive kinase which may activate the phosphorylation-dependent protective function of mammalian 27-kDa heat-shock protein HSP27. Eur. J. Biochem. 227, 416-427 (1995).
143. i-dependent activation. J. Biol. Chem. 276, 19395-19400 (2000).
144. Nakano, A., Cohen, M. V., Critz, S. & Downey, J. M. SB 203580, an inhibitor of p38 MAPK, abolishes infarct-limiting effect of ischemic preconditioning in isolated rabbit hearts. Basic Res. Cardiol. 95, 466-471 (2000).
145. Mocanu, M. M., Baxter, G. F., Yue, Y., Critz, S. D. & Yellon, D. M. The p38 MAPK inhibitor, SB203580, abrogates ischaemic preconditioning in rat heart but timing of administration is critical. Basic Res. Cardiol. 95, 472-478 (2000).
146. Ma, X. L. et al. Inhibition of p38 mitogen-activated protein kinase decreases cardiomyocyte apoptosis and improves cardiac function after myocardial ischemia and reperfusion. Circulation 99, 1685-1691 (1999).
147. Barancik, M., Htun, P., Strohm, C., Kilian, S. & Schaper, W. Inhibition of the cardiac p38-MAPK pathway by SB203580 delays ischemic cell death. J. Cardiovasc. Pharmacol. 35, 474-483 (2000).
148. Martin, J. L., Avkiran, M., Quinlan, R. A., Cohen, P. & Marber, M. S. Antiischemic effects of SB203580 are mediated through the inhibition of p38alpha mitogen-activated protein kinase: Evidence from ectopic expression of an inhibition-resistant kinase. Circ. Res. 89, 750-752 (2001).
149. Saurin, A. T. et al. The role of differential activation of p38-mitogen-activated protein kinase in preconditioned ventricuiar myocytes. FASEB J. 14, 2237-2246 (2000).
150. Takeishi, Y. et al. Differential regulation of p90 ribosomal S6 kinase and big mitogen-activated protein kinase 1 by ischemia/reperfusion and oxidative stress in perfused guinea pig hearts. Circ. Res. 85, 1164-1172 (1999).
151. Takeishi, Y. et al. Src and multiple MAP kinase activation in cardiac hypertrophy and congestive heart failure under chronic pressure-overload: comparison with acute mechanical stretch. J. Mol. Cell. Cardiol. 33, 1637-1648 (2001).
152. Takeishi, Y. et al. Src family kinase and adenosine differentially regulate multiple MAP kinases in ischemic myocardium: modulation of MAP kinases activation by ischemic preconditioning. J. Mol. Cell. Cardiol. 33, 1989-2005 (2001).
153. Hirota, H. et al. Loss of a gp130 cardiac muscle cell survival pathway is a critical event in the onset of heart failure during biomechanical stress. Cell 97, 189-198 (1999).
154. Nicol, R. L. et al. Activated MEK5 induces serial assembly of sarcomeres and eccentric cardiac hypertrophy. EMBO J. 20, 2757-2767 (2001).
155. Takeishi, Y. et al. Activation of mitogen-activated protein kinases and p90 ribosomal S6 kinase in failing human hearts with dilated cardiomyopathy. Cardiovasc. Res. 53, 131-137 (2002).
156. Wollert, K. C. et al. Cardiotrophin-1 activates a distinct form of cardiac muscle cell hypertrophy. Assembly of sarcomeric units in series via gp130/leukemia inhibitory factor receptor-dependent pathways. J. Biol. Chem. 271, 9535-9545 (1996).
157. Jirousek, M. R. et al (S)-13-[(dimethylamino)methyl]-10,11,14,15-tetrahydro-4,9:16, 21- dimetheno-1H, 13H-dibenzo[e,k]pyrrolo[3,4-h][1,4,13]oxadiazacyclohexadecene-1,3(2H -dione (LY333531) and related analogues: isozyme selective inhibitors of protein kinase C β. J. Med. Chem. 39, 2664-2671 (1996).
158. The Criteria Committee of the New York Heart Association, Nomenclature and Criteria for Diagnosis of Diseases of the Heart and Great Vessels, 253-256 (Little, Brown, and Co, Boston, Massachusetts, USA, 1994).
159. Swynghedauw, B. Molecular mechanisms of myocardial remodeling. Physiol. Rev. 79, 215-262 (1999).
160. Sadoshima, J. & Izumo, S. The cellular and molecular response of cardiac myocytes to mechanical stress. Annu. Rev. Physiol. 59, 551-571 (1997).