A cardiac-enriched microRNA, miR-378, blocks cardiac hypertrophy by targeting Ras signaling

Journal of Biological Chemistry

Volumn 288, Issue 16, 2013, Pages 11216-11232

  Nagalingam, Raghu S ^a   Sundaresan, Nagalingam R ^b   Gupta, Mahesh P ^b   Geenen, David L ^a   Solaro, R John ^a   Gupta, Madhu ^a  

^a UNIVERSITY OF ILLINOIS AT CHICAGO   (United States)

^b UNIVERSITY OF CHICAGO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIVITY-DEPENDENT; CARDIAC HYPERTROPHY; CARDIAC REMODELING; MICRORNAS; NEGATIVE REGULATORS; SIGNALING CASCADES;

GENE EXPRESSION; PATHOLOGY; RNA;

HEART;

GLYCOGEN SYNTHASE KINASE 3BETA; GROWTH FACTOR RECEPTOR BOUND PROTEIN 2; MICRORNA; MICRORNA 378; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; MITOGEN ACTIVATED PROTEIN KINASE KINASE 1; PHENYLEPHRINE; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; RAS PROTEIN; S6 KINASE; TRANSCRIPTION FACTOR NFAT; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; CELL CULTURE; CELL NUCLEUS; CONTROLLED STUDY; DOWN REGULATION; ENZYME ACTIVATION; ENZYME PHOSPHORYLATION; GENE EXPRESSION; GENE OVEREXPRESSION; GENE SILENCING; HEART MUSCLE CELL; HEART VENTRICLE HYPERTROPHY; HUMAN; HUMAN CELL; INHIBITION KINETICS; NEWBORN; NONHUMAN; NUCLEOTIDE SEQUENCE; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN DEFICIENCY; PROTEIN TARGETING; RAT; SIGNAL TRANSDUCTION;

ADRENERGIC ALPHA-1 RECEPTOR AGONISTS; ANIMALS; CARDIOMEGALY; CELLS, CULTURED; GENE EXPRESSION REGULATION; GLYCOGEN SYNTHASE KINASE 3; GRB2 ADAPTOR PROTEIN; MAP KINASE KINASE 1; MAP KINASE KINASE KINASES; MAP KINASE SIGNALING SYSTEM; MICRORNAS; MITOGEN-ACTIVATED PROTEIN KINASE 3; MUSCLE PROTEINS; PHENYLEPHRINE; PHOSPHATIDYLINOSITOL 3-KINASES; PROTO-ONCOGENE PROTEINS C-AKT; RAS PROTEINS; RATS; RATS, SPRAGUE-DAWLEY;

EID: 84876553780     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M112.442384     Document Type: Article

References (87)

1. Hennersdorf, M. G., and Strauer, B. E. (2001) Arterial hypertension and cardiac arrhythmias. J. Hypertens. 19, 167-177.
2. Vakili, B. A., Okin, P. M., and Devereux, R. B. (2001) Prognostic implications of left ventricular hypertrophy. Am. Heart J. 141, 334-341.
3. Frey, N., Katus, H. A., Olson, E. N., and Hill, J. A. (2004) Hypertrophy of the heart. A new therapeutic target? Circulation 109, 1580-1589.
4. Heineke, J., and Molkentin, J. D. (2006) Regulation of cardiac hypertrophy by intracellular signalling pathways. Nat. Rev. Mol. Cell Biol. 7, 589-600.
5. Sugden, P. H., and Clerk, A. (2000) Activation of the small GTP-binding protein Ras in the heart by hypertrophic agonists. Trends Cardiovasc. Med. 10, 1-8.
6. Dorn, G. W., 2nd, and Force, T. (2005) Protein kinase cascades in the regulation of cardiac hypertrophy. J. Clin. Invest. 115, 527-537.
7. Malumbres, M., and Barbacid, M. (2003) RAS oncogenes. The first 30 years. Nat. Rev. Cancer 3, 459-465.
8. Hunter, J. J., Tanaka, N., Rockman, H. A., Ross, J., Jr., and Chien, K. R. (1995) Ventricular expression of a MLC-2v-ras fusion gene induces cardiac hypertrophy and selective diastolic dysfunction in transgenic mice. J. Biol. Chem. 270, 23173-23178.
9. Ho, P. D., Zechner, D. K., He, H., Dillmann, W. H., Glembotski, C. C., and McDonough, P. M. (1998) The Raf-MEK-ERK cascade represents a common pathway for alteration of intracellular calcium by Ras and protein kinase C in cardiac myocytes. J. Biol. Chem. 273, 21730-21735.
10. Harris, I. S., Zhang, S., Treskov, I., Kovacs, A., Weinheimer, C., and Muslin, A. J. (2004) Raf-1 kinase is required for cardiac hypertrophy and cardiomyocyte survival in response to pressure overload. Circulation 110, 718-723.
11. Mitchell, S., Ota, A., Foster, W., Zhang, B., Fang, Z., Patel, S., Nelson, S. F., Horvath, S., and Wang, Y. (2006) Distinct gene expression profiles in adult mouse heart following targeted MAP kinase activation. Physiol. Genomics 25, 50-59.
12. Small, E. M., Frost, R. J., and Olson, E. N. (2010) MicroRNAs add a new dimension to cardiovascular disease. Circulation 121, 1022-1032.
13. Dimmeler, S., and Zeiher, A. M. (2010) Circulating microRNAs. Novel biomarkers for cardiovascular diseases? Eur Heart J 31, 2705-2707.
14. Knezevic, I., Patel, A., Sundaresan, N. R., Gupta, M. P., Solaro, R. J., Nagalingam, R. S., and Gupta, M. (2012) A novel cardiomyocyte-enriched microRNA, miR-378, targets insulin-like growth factor 1 receptor. Implications in postnatal cardiac remodeling and cell survival. J. Biol. Chem. 287, 12913-12926.
15. Gupta, M., Zak, R., Libermann, T. A., and Gupta, M. P. (1998) Tissuerestricted expression of the cardiac α-myosin heavy chain gene is controlled by a downstream repressor element containing a palindrome of two ets-binding sites. Mol. Cell. Biol. 18, 7243-7258.
16. Zarich, N., Oliva, J. L., Martínez, N., Jorge, R., Ballester, A., Gutiérrez-Eisman, S., García-Vargas, S., and Rojas, J. M. (2006) Grb2 is a negative modulator of the intrinsic Ras-GEF activity of hSos1. Mol. Biol. Cell 17, 3591-3597.
17. Sundaresan, N. R., Pillai, V. B., Wolfgeher, D., Samant, S., Vasudevan, P., Parekh, V., Raghuraman, H., Cunningham, J. M., Gupta, M., and Gupta, M. P. (2011) The deacetylase SIRT1 promotes membrane localization and activation of Akt and PDK1 during tumorigenesis and cardiac hypertrophy. Sci. Signal. 4, ra46.
18. Ocampo, C., Ingram, P., Ilbawi, M., Arcilla, R., and Gupta, M. (2003) Revisiting the surgical creation of volume load by aorto-caval shunt in rats. Mol. Cell. Biochem. 251, 139-143.
19. Sundaresan, N. R., Vasudevan, P., Zhong, L., Kim, G., Samant, S., Parekh, V., Pillai, V. B., Ravindra, P. V., Gupta, M., Jeevanandam, V., Cunningham, J. M., Deng, C. X., Lombard, D. B., Mostoslavsky, R., and Gupta, M. P. (2012) The sirtuin SIRT6 blocks IGF-Akt signaling and development of cardiac hypertrophy by targeting c-Jun. Nat. Med. 18, 1643-1650.
20. Gupta, M. P., Samant, S. A., Smith, S. H., and Shroff, S. G. (2008) HDAC4 and PCAF bind to cardiac sarcomeres and play a role in regulating myofilament contractile activity. J. Biol. Chem. 283, 10135-10146.
21. Sundaresan, N. R., Gupta, M., Kim, G., Rajamohan, S. B., Isbatan, A., and Gupta, M. P. (2009) Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice. J. Clin. Invest. 119, 2758-2771.
22. Freire, G., Ocampo, C., Ilbawi, N., Griffin, A. J., and Gupta, M. (2007) Overt expression of AP-1 reduces α myosin heavy chain expression and contributes to heart failure from chronic volume overload. J. Mol. Cell. Cardiol. 43, 465-478.
23. Pillai, V. B., Sundaresan, N. R., Kim, G., Gupta, M., Rajamohan, S. B., Pillai, J. B., Samant, S., Ravindra, P. V., Isbatan, A., and Gupta, M. P. (2010) Exogenous NAD+ blocks cardiac hypertrophic response via activation of the SIRT3-LKB1-AMP-activated kinase pathway. J. Biol. Chem. 285, 3133-3144.
24. Hogan, P. G., Chen, L., Nardone, J., and Rao, A. (2003) Transcriptional regulation by calcium, calcineurin, and NFAT. Genes Dev. 17, 2205-2232.
25. Gingras, A. C., Raught, B., and Sonenberg, N. (2001) Regulation of translation initiation by FRAP/mTOR. Genes Dev. 15, 807-826.
26. Pyronnet, S. (2000) Phosphorylation of the cap-binding protein eIF4E by the MAP K-activated protein kinase Mnk1. Biochem. Pharmacol. 60, 1237-1243.
27. Barron, A. J., Finn, S. G., and Fuller, S. J. (2003) Chronic activation of extracellular signal-regulated protein kinases by phenylephrine is required to elicit a hypertrophic response in cardiac myocytes. Biochem. J. 371, 71-79.
28. Sugden, P. H., Fuller, S. J., Weiss, S. C., and Clerk, A. (2008) Glycogen synthase kinase 3 (GSK3) in the heart. A point of integration in hypertrophic signalling and a therapeutic target? A critical analysis. Br. J. Pharmacol. 153, S137-153.
29. Proud, C. G. (2004) Ras, PI3-kinase and mTOR signaling in cardiac hypertrophy. Cardiovasc. Res. 63, 403-413.
30. Sugden, P. H. (2003) Ras, Akt, and mechanotransduction in the cardiac myocyte. Circ. Res. 93, 1179-1192.
31. Ciuffini, L., Castellani, L., Salvati, E., Galletti, S., Falcone, G., and Alemà, S. (2008) Delineating v-Src downstream effector pathways in transformed myoblasts. Oncogene 27, 528-539.
32. Lewis, B. P., Burge, C. B., and Bartel, D. P. (2005) Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120, 15-20.
33. Krek, A., Grün, D., Poy, M. N., Wolf, R., Rosenberg, L., Epstein, E. J., MacMenamin, P., da Piedade, I., Gunsalus, K. C., Stoffel, M., and Rajewsky, N. (2005) Combinatorial microRNA target predictions. Nat. Genet. 37, 495-500.
34. Maragkakis, M., Reczko, M., Simossis, V. A., Alexiou, P., Papadopoulos, G. L., Dalamagas, T., Giannopoulos, G., Goumas, G., Koukis, E., Kourtis, K., Vergoulis, T., Koziris, N., Sellis, T., Tsanakas, P., and Hatzigeorgiou, A. G. (2009) DIANA-microT web server. Elucidating microRNA functions through target prediction. Nucleic Acids Res. 37, W273-276.
35. Betel, D., Wilson, M., Gabow, A., Marks, D. S., and Sander, C. (2008) The microRNA.org resource. Targets and expression. Nucleic Acids Res. 36, D149-153.
36. John, B., Enright, A. J., Aravin, A., Tuschl, T., Sander, C., and Marks, D. S. (2004) Human microRNA targets. PLoS Biol. 2, e363.
37. Lowenstein, E. J., Daly, R. J., Batzer, A. G., Li, W., Margolis, B., Lammers, R., Ullrich, A., Skolnik, E. Y., Bar-Sagi, D., and Schlessinger, J. (1992) The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling. Cell 70, 431-442.
38. Zhang, S., Weinheimer, C., Courtois, M., Kovacs, A., Zhang, C. E., Cheng, A. M., Wang, Y., and Muslin, A. J. (2003) The role of the Grb2-p38 MAP K signaling pathway in cardiac hypertrophy and fibrosis. J. Clin. Invest. 111, 833-841.
39. Nguyen, A., Burack, W. R., Stock, J. L., Kortum, R., Chaika, O. V., Afkarian, M., Muller, W. J., Murphy, K. M., Morrison, D. K., Lewis, R. E., McNeish, J., and Shaw, A. S. (2002) Kinase suppressor of Ras (KSR) is a scaffold which facilitates mitogen-activated protein kinase activation in vivo. Mol. Cell. Biol. 22, 3035-3045.
40. Lee, C. H., Della, N. G., Chew, C. E., and Zack, D. J. (1996) Rin, a neuronspecific and calmodulin-binding small G-protein, and Rit define a novel subfamily of Ras proteins. J. Neurosci. 16, 6784-6794.
41. Stone, J. C. (2011) Regulation and function of the RasGRP family of Ras activators in blood cells. Genes Cancer 2, 320-334.
42. Yang, Y., Li, L., Wong, G. W., Krilis, S. A., Madhusudhan, M. S., Sali, A., and Stevens, R. L. (2002) RasGRP4, a new mast cell-restricted Ras guanine nucleotide-releasing protein with calcium- and diacylglycerol-binding motifs. Identification of defective variants of this signaling protein in asthma, mastocytosis, and mast cell leukemia patients and demonstration of the importance of RasGRP4 in mast cell development and function. J. Biol. Chem. 277, 25756-25774.
43. Ebinu, J. O., Bottorff, D. A., Chan, E. Y., Stang, S. L., Dunn, R. J., and Stone, J. C. (1998) RasGRP, a Ras guanyl nucleotide-releasing protein with calcium- and diacylglycerol-binding motifs. Science 280, 1082-1086.
44. Schlaepfer, D. D., Hanks, S. K., Hunter, T., and van der Geer, P. (1994) Integrin-mediated signal transduction linked to Ras pathway by GRB2 binding to focal adhesion kinase. Nature 372, 786-791.
45. Torsoni, A. S., Constancio, S. S., Nadruz, W., Jr., Hanks, S. K., and Franchini, K. G. (2003) Focal adhesion kinase is activated and mediates the early hypertrophic response to stretch in cardiac myocytes. Circ. Res. 93, 140-147.
46. DiMichele, L. A., Doherty, J. T., Rojas, M., Beggs, H. E., Reichardt, L. F., Mack, C. P., and Taylor, J. M. (2006) Myocyte-restricted focal adhesion kinase deletion attenuates pressure overload-induced hypertrophy. Circ. Res. 99, 636-645.
47. Thum, T., Gross, C., Fiedler, J., Fischer, T., Kissler, S., Bussen, M., Galuppo, P., Just, S., Rottbauer, W., Frantz, S., Castoldi, M., Soutschek, J., Koteliansky, V., Rosenwald, A., Basson, M. A., Licht, J. D., Pena, J. T., Rouhanifard, S. H., Muckenthaler, M. U., Tuschl, T., Martin, G. R., Bauersachs, J., and Engelhardt, S. (2008) MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature 456, 980-984.
48. Sayed, D., Rane, S., Lypowy, J., He, M., Chen, I. Y., Vashistha, H., Yan, L., Malhotra, A., Vatner, D., and Abdellatif, M. (2008) MicroRNA-21 targets Sprouty2 and promotes cellular outgrowths. Mol. Biol. Cell 19, 3272-3282.
49. Casci, T., Vinós, J., and Freeman, M. (1999) Sprouty, an intracellular inhibitor of Ras signaling. Cell 96, 655-665.
50. Carrer, M., Liu, N., Grueter, C. E., Williams, A. H., Frisard, M. I., Hulver, M. W., Bassel-Duby, R., and Olson, E. N. (2012) Control of mitochondrial metabolism and systemic energy homeostasis by microRNAs 378 and 378*. Proc. Natl. Acad. Sci. U.S.A. 109, 15330-15335.
51. Sayed, D., Hong, C., Chen, I. Y., Lypowy, J., and Abdellatif, M. (2007) MicroRNAs play an essential role in the development of cardiac hypertrophy. Circ. Res. 100, 416-424.
52. van Rooij, E., Sutherland, L. B., Thatcher, J. E., DiMaio, J. M., Naseem, R. H., Marshall, W. S., Hill, J. A., and Olson, E. N. (2008) Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis. Proc. Natl. Acad. Sci. U.S.A. 105, 13027-13032.
53. Duisters, R. F., Tijsen, A. J., Schroen, B., Leenders, J. J., Lentink, V., van der Made, I., Herias, V., van Leeuwen, R. E., Schellings, M. W., Barenbrug, P., Maessen, J. G., Heymans, S., Pinto, Y. M., and Creemers, E. E. (2009) miR-133 and miR-30 regulate connective tissue growth factor. Implications for a role of microRNAs in myocardial matrix remodeling. Circ. Res. 104, 170-178.
54. Callis, T. E., Pandya, K., Seok, H. Y., Tang, R. H., Tatsuguchi, M., Huang, Z. P., Chen, J. F., Deng, Z., Gunn, B., Shumate, J., Willis, M. S., Selzman, C. H., and Wang, D. Z. (2009) MicroRNA-208a is a regulator of cardiac hypertrophy and conduction in mice. J. Clin. Invest. 119, 2772-2786.
55. Haghikia, A., Missol-Kolka, E., Tsikas, D., Venturini, L., Brundiers, S., Castoldi, M., Muckenthaler, M. U., Eder, M., Stapel, B., Thum, T., Haghikia, A., Petrasch-Parwez, E., Drexler, H., Hilfiker-Kleiner, D., and Scherr, M. (2011) Signal transducer and activator of transcription 3-mediated regulation of miR-199a-5p links cardiomyocyte and endothelial cell function in the heart. A key role for ubiquitin-conjugating enzymes. Eur. Heart J. 32, 1287-1297.
56. Rane, S., He, M., Sayed, D., Yan, L., Vatner, D., and Abdellatif, M. (2010) An antagonism between the AKT and β-adrenergic signaling pathways mediated through their reciprocal effects on miR-199a-5p. Cell. Signal. 22, 1054-1062.
57. da Costa Martins, P. A., Salic, K., Gladka, M. M., Armand, A. S., Leptidis, S., el Azzouzi, H., Hansen, A., Coenende Roo, C. J., Bierhuizen, M. F., van der Nagel, R., van Kuik, J., de Weger, R., de Bruin, A., Condorelli, G., Arbones, M. L., Eschenhagen, T., and De Windt, L. J. (2010) MicroRNA- 199b targets the nuclear kinase Dyrk1a in an auto-amplification loop promoting calcineurin/NFAT signalling. Nat. Cell. Biol. 12, 1220-1227.
58. Lin, Z., Murtaza, I., Wang, K., Jiao, J., Gao, J., and Li, P. F. (2009) miR-23a functions downstream of NFATc3 to regulate cardiac hypertrophy. Proc. Natl. Acad. Sci. U.S.A. 106, 12103-12108.
59. van Rooij, E., Sutherland, L. B., Liu, N., Williams, A. H., McAnally, J., Gerard, R. D., Richardson, J. A., and Olson, E. N. (2006) A signature pattern of stress-responsive microRNAs that can evoke cardiac hypertrophy and heart failure. Proc. Natl. Acad. Sci. U.S.A. 103, 18255-18260.
60. Sucharov, C., Bristow, M. R., and Port, J. D. (2008) miRNA expression in the failing human heart: functional correlates. J. Mol. Cell. Cardiol. 45, 185-192.
61. Ucar, A., Gupta, S. K., Fiedler, J., Erikci, E., Kardasinski, M., Batkai, S., Dangwal, S., Kumarswamy, R., Bang, C., Holzmann, A., Remke, J., Caprio, M., Jentzsch, C., Engelhardt, S., Geisendorf, S., Glas, C., Hofmann, T. G., Nessling, M., Richter, K., Schiffer, M., Carrier, L., Napp, L. C., Bauersachs, J., Chowdhury, K., and Thum, T. (2012) The miRNA-212/132 family regulates both cardiac hypertrophy and cardiomyocyte autophagy. Nat. Commun. 3, 1078.
62. Yang, Y., Ago, T., Zhai, P., Abdellatif, M., and Sadoshima, J. (2011) Thioredoxin 1 negatively regulates angiotensin II-induced cardiac hypertrophy through up-regulation of miR-98/let-7. Circ. Res. 108, 305-313.
63. Elia, L., Contu, R., Quintavalle, M., Varrone, F., Chimenti, C., Russo, M. A., Cimino, V., De Marinis, L., Frustaci, A., Catalucci, D., and Condorelli, G. (2009) Reciprocal regulation of microRNA-1 and insulin-like growth factor-1 signal transduction cascade in cardiac and skeletal muscle in physiological and pathological conditions. Circulation 120, 2377-2385.
64. Ikeda, S., He, A., Kong, S. W., Lu, J., Bejar, R., Bodyak, N., Lee, K. H., Ma, Q., Kang, P. M., Golub, T. R., and Pu, W. T. (2009) MicroRNA-1 negatively regulates expression of the hypertrophy-associated calmodulin and Mef2a genes. Mol. Cell. Biol. 29, 2193-2204.
65. Carè, A., Catalucci, D., Felicetti, F., Bonci, D., Addario, A., Gallo, P., Bang, M. L., Segnalini, P., Gu, Y., Dalton, N. D., Elia, L., Latronico, M. V., Høydal, M., Autore, C., Russo, M. A., Dorn, G. W., 2nd, Ellingsen, O., Ruiz-Lozano, P., Peterson, K. L., Croce, C. M., Peschle, C., and Condorelli, G. (2007) MicroRNA-133 controls cardiac hypertrophy. Nat. Med. 13, 613-618.
66. Li, Q., Lin, X., Yang, X., and Chang, J. (2010) NFATc4 is negatively regulated in miR-133a-mediated cardiomyocyte hypertrophic repression. Am. J. Physiol. Heart Circ. Physiol. 298, H1340-1347.
67. Matkovich, S. J., Wang, W., Tu, Y., Eschenbacher, W. H., Dorn, L. E., Condorelli, G., Diwan, A., Nerbonne, J. M., and Dorn, G. W., 2nd (2010) MicroRNA-133a protects against myocardial fibrosis and modulates electrical repolarization without affecting hypertrophy in pressure-overloaded adult hearts. Circ. Res. 106, 166-175.
68. Dong, D. L., Chen, C., Huo, R., Wang, N., Li, Z., Tu, Y. J., Hu, J. T., Chu, X., Huang, W., and Yang, B. F. (2010) Reciprocal repression between microRNA-133 and calcineurin regulates cardiac hypertrophy. A novel mechanism for progressive cardiac hypertrophy. Hypertension 55, 946-952.
69. Wang, K., Long, B., Zhou, J., and Li, P. F. (2010) miR-9 and NFATc3 regulate myocardin in cardiac hypertrophy. J. Biol. Chem. 285, 11903-11912.
70. Li, Q., Song, X. W., Zou, J., Wang, G. K., Kremneva, E., Li, X. Q., Zhu, N., Sun, T., Lappalainen, P., Yuan, W. J., Qin, Y. W., and Jing, Q. (2010) Attenuation of microRNA-1 derepresses the cytoskeleton regulatory protein twinfilin-1 to provoke cardiac hypertrophy. J. Cell Sci. 123, 2444-2452.
71. Obata, K., Nagata, K., Iwase, M., Odashima, M., Nagasaka, T., Izawa, H., Murohara, T., Yamada, Y., and Yokota, M. (2005) Overexpression of cal-modulin induces cardiac hypertrophy by a calcineurin-dependent pathway. Biochem. Biophys. Res. Commun. 338, 1299-1305.
72. Liu, N., Bezprozvannaya, S., Williams, A. H., Qi, X., Richardson, J. A., Bassel-Duby, R., and Olson, E. N. (2008) microRNA-133a regulates cardiomyocyte proliferation and suppresses smooth muscle gene expression in the heart. Genes Dev. 22, 3242-3254.
73. Hua, Y., Zhang, Y., and Ren, J. (2012) IGF-1 deficiency resists cardiac hypertrophy and myocardial contractile dysfunction. Role of microRNA-1 and microRNA-133a. J Cell Mol Med 16, 83-95.
74. Matsui, T., Li, L., Wu, J. C., Cook, S. A., Nagoshi, T., Picard, M. H., Liao, R., and Rosenzweig, A. (2002) Phenotypic spectrum caused by transgenic overexpression of activated Akt in the heart. J. Biol. Chem. 277, 22896-22901.
75. Matsui, T., Nagoshi, T., and Rosenzweig, A. (2003) Akt and PI 3-kinase signaling in cardiomyocyte hypertrophy and survival. Cell Cycle 2, 220-223.
76. Sanna, B., Bueno, O. F., Dai, Y. S., Wilkins, B. J., and Molkentin, J. D. (2005) Direct and indirect interactions between calcineurin-NFAT and MEK1-extracellular signal-regulated kinase 1/2 signaling pathways regulate cardiac gene expression and cellular growth. Mol. Cell. Biol. 25, 865-878.
77. Denayer, E., and Legius, E. (2007) What's new in the neurocardiofacial cutaneous syndromes? Eur. J. Pediatr. 166, 1091-1098.
78. Tidyman, W. E., and Rauen, K. A. (2009) The RASopathies. Developmental syndromes of Ras/MAP K pathway dysregulation. Curr. Opin. Genet. Dev. 19, 230-236.
79. Tartaglia, M., Martinelli, S., Stella, L., Bocchinfuso, G., Flex, E., Cordeddu, V., Zampino, G., Burgt, I. V., Palleschi, A., Petrucci, T. C., Sorcini, M., Schoch, C., Foa, R., Emanuel, P. D., and Gelb, B. D. (2006) Diversity and functional consequences of germline and somatic PTPN11 mutations in human disease. Am. J. Hum. Genet. 78, 279-290.
80. Roberts, A. E., Araki, T., Swanson, K. D., Montgomery, K. T., Schiripo, T. A., Joshi, V. A., Li, L., Yassin, Y., Tamburino, A. M., Neel, B. G., and Kucherlapati, R. S. (2007) Germline gain-of-function mutations in SOS1 cause Noonan syndrome. Nat. Genet. 39, 70-74.
81. Schubbert, S., Zenker, M., Rowe, S. L., Böll, S., Klein, C., Bollag, G., van der Burgt, I., Musante, L., Kalscheuer, V., Wehner, L. E., Nguyen, H., West, B., Zhang, K. Y., Sistermans, E., Rauch, A., Niemeyer, C. M., Shannon, K., and Kratz, C. P. (2006) Germline KRAS mutations cause Noonan syndrome. Nat. Genet. 38, 331-336.
82. Pandit, B., Sarkozy, A., Pennacchio, L. A., Carta, C., Oishi, K., Martinelli, S., Pogna, E. A., Schackwitz, W., Ustaszewska, A., Landstrom, A., Bos, J. M., Ommen, S. R., Esposito, G., Lepri, F., Faul, C., Mundel, P., López Siguero, J. P., Tenconi, R., Selicorni, A., Rossi, C., Mazzanti, L., Torrente, I., Marino, B., Digilio, M. C., Zampino, G., Ackerman, M. J., Dallapiccola, B., Tartaglia, M., and Gelb, B. D. (2007) Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy. Nat. Genet. 39, 1007-1012.
83. Wu, X., Simpson, J., Hong, J. H., Kim, K. H., Thavarajah, N. K., Backx, P. H., Neel, B. G., and Araki, T. (2011) MEK-ERK pathway modulation ameliorates disease phenotypes in a mouse model of Noonan syndrome associated with the Raf1(L613V) mutation. J. Clin. Invest. 121, 1009-1025.
84. Marin, T. M., Keith, K., Davies, B., Conner, D. A., Guha, P., Kalaitzidis, D., Wu, X., Lauriol, J., Wang, B., Bauer, M., Bronson, R., Franchini, K. G., Neel, B. G., and Kontaridis, M. I. (2011) Rapamycin reverses hypertrophic cardiomyopathy in a mouse model of LEOPARD syndrome-associated PTPN11 mutation. J. Clin. Invest. 121, 1026-1043.
85. Krenz, M., Gulick, J., Osinska, H. E., Colbert, M. C., Molkentin, J. D., and Robbins, J. (2008) Role of ERK1/2 signaling in congenital valve malformations in Noonan syndrome. Proc. Natl. Acad. Sci. U.S.A. 105, 18930-18935.
86. Nakamura, T., Colbert, M., Krenz, M., Molkentin, J. D., Hahn, H. S., Dorn, G. W., 2nd, and Robbins, J. (2007) Mediating ERK 1/2 signaling rescues congenital heart defects in a mouse model of Noonan syndrome. J. Clin. Invest. 117, 2123-2132.
87. Nakamura, T., Gulick, J., Pratt, R., and Robbins, J. (2009) Noonan syndrome is associated with enhanced pERK activity, the repression of which can prevent craniofacial malformations. Proc. Natl. Acad. Sci. U.S.A. 106, 15436-15441.