dc.creatorMarin T.M.
dc.creatorClemente C.F.M.Z.
dc.creatorSantos A.M.
dc.creatorPicardi P.K.
dc.creatorPascoal V.D.B.
dc.creatorLopes-Cendes I.
dc.creatorSaad M.J.A.
dc.creatorFranchini K.G.
dc.date2008
dc.date2015-06-30T19:28:53Z
dc.date2015-11-26T14:44:34Z
dc.date2015-06-30T19:28:53Z
dc.date2015-11-26T14:44:34Z
dc.date.accessioned2018-03-28T21:53:26Z
dc.date.available2018-03-28T21:53:26Z
dc.identifier
dc.identifierCirculation Research. , v. 103, n. 8, p. 813 - 824, 2008.
dc.identifier97330
dc.identifier10.1161/CIRCRESAHA.108.179754
dc.identifierhttp://www.scopus.com/inward/record.url?eid=2-s2.0-54449101472&partnerID=40&md5=d5a9e00b9d3790f329e80c27d6ffe535
dc.identifierhttp://www.repositorio.unicamp.br/handle/REPOSIP/106408
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/106408
dc.identifier2-s2.0-54449101472
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1252175
dc.descriptionThe aim of this study was to investigate whether Shp2 (Src homology region 2, phosphatase 2) controls focal adhesion kinase (FAK) activity and its trophic actions in cardiomyocytes. We show that low phosphorylation levels of FAK in nonstretched neonatal rat ventricular myocytes (NRVMs) coincided with a relatively high basal association of FAK with Shp2 and Shp2 phosphatase activity. Cyclic stretch (15% above initial length) enhanced FAK phosphorylation at Tyr397 and reduced FAK/Shp2 association and phosphatase activity in anti-Shp2 precipitates. Recombinant Shp2 C-terminal protein tyrosine phosphatase domain (Shp2-PTP) interacted with nonphosphorylated recombinant FAK and dephosphorylated FAK immunoprecipitated from NRVMs. Depletion of Shp2 by specific small interfering RNA increased the phosphorylation of FAK Tyr397, Src Tyr418, AKT Ser473, TSC2 Thr1462, and S6 kinase Thr389 and induced hypertrophy of nonstretched NRVMs. Inhibition of FAK/Src activity by PP2 {4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine} abolished the phosphorylation of AKT, TSC2, and S6 kinase, as well as the hypertrophy of NRVMs induced by Shp2 depletion. Inhibition of mTOR (mammalian target of rapamycin) with rapamycin blunted the hypertrophy in NRVMs depleted of Shp2. NRVMs treated with PP2 or depleted of FAK by specific small interfering RNA were defective in FAK, Src, extracellular signal-regulated kinase, AKT, TSC2, and S6 kinase phosphorylation, as well as in the hypertrophic response to prolonged stretch. The stretch-induced hypertrophy of NRVMs was also prevented by rapamycin. These findings demonstrate that basal Shp2 tyrosine phosphatase activity controls the size of cardiomyocytes by downregulating a pathway that involves FAK/Src and mTOR signaling pathways. © 2008 American Heart Association, Inc.
dc.description103
dc.description8
dc.description813
dc.description824
dc.descriptionHeineke, J., Molkentin, J.D., Regulation of cardiac hypertrophy by intra-cellular signalling pathways (2006) Nat Rev Mol Cell Biol, 7, pp. 589-600
dc.descriptionEble, D.M., Strait, J.B., Govindarajan, G., Lou, J., Byron, K.L., Samarel, A.M., Endothelin-induced cardiomyocyte hypertrophy: Role for focal adhesion kinase (2000) Am J Physiol, 278, pp. H1695-H1707
dc.descriptionTaylor, J.M., Rovin, J.D., Parsons, J.T., A role for focal adhesion kinase in phenylephrine-induced hypertrophy of rat ventricular cardiomyocytes (2000) J Biol Chem, 275, pp. 19250-19257
dc.descriptionTorsoni, A.S., Constancio, S.S., Nadruz Jr.W, Hanks, S.K., Franchini, K.G., Focal adhesion kinase is activated and mediates the early hypertrophic response to stretch in cardiomyocytes (2003) Circ Res, 93, pp. 140-147
dc.descriptionTorsoni, A.S., Marin, T.M., Velloso, L.A., Franchini, K.G., RhoA/ROCK signaling is critical to FAK activation by cyclic stretch in cardiomyocytes (2005) Am J Physiol, 289, pp. H1488-H1496
dc.descriptionNadruz Jr.W, Corat, M.A., Marin, T.M., Guimaraes Pereira, G.A., Franchini, K.G., Focal adhesion kinase mediates MEF2 and c-Jun activation by stretch: Role in the activation of the cardiac hypertrophic genetic program (2005) Cardiovasc Res, 68, pp. 87-97
dc.descriptionFranchini, K.G., Torsoni, A.S., Soares, P.H., Saad, M.J., Early activation of the multicomponent signaling complex associated with focal adhesion kinase induced by pressure overload in the rat heart (2000) Circ Res, 87, pp. 558-565
dc.descriptionPham, C.G., Harpf, A.E., Keller, R.S., Vu, H.T., Shai, S.Y., Loftus, J.C., Ross, R.S., Striated muscle-specific beta(1D)-integrin and FAK are involved in car-diomyocyte hypertrophic response pathway (2000) Am J Physiol, 279, pp. H2916-H2926
dc.descriptionPeng, X., Kraus, M.S., Wei, H., Shen, T.L., Pariaut, R., Alcaraz, A., Ji, G., Guan, J.L., Inactivation of focal adhesion kinase in cardiomyocytes promotes eccentric cardiac hypertrophy and fibrosis in mice (2006) J Clin Invest, 116, pp. 217-227
dc.descriptionDimichele, L.A., Doherty, J.T., Rojas, M., Beggs, H.E., Reichardt, L.F., MacK, C.P., Taylor, J.M., Myocyte-restricted focal adhesion kinase deletion attenuates pressure overload-induced hypertrophy (2006) Circ Res, 99, pp. 636-645
dc.descriptionClemente, C.F., Tornatore, T.F., Theizen, T.H., Deckmann, A.C., Pereira, T.C., Lopes-Cendes, I., Souza, J.R., Franchini, K.G., Targeting focal adhesion kinase with small interfering RNA prevents and reverses load-induced cardiac hypertrophy in mice (2007) Circ Res, 101, pp. 1339-1348
dc.descriptionDunty, J.M., Schaller, M.D., The N termini of focal adhesion kinase family members regulate substrate phosphorylation, localization, and cell morphology (2002) J Biol Chem, 277, pp. 45644-45654
dc.descriptionFonseca, P.M., Inoue, R.Y., Kobarg, C.B., Crosara-Alberto, D.P., Kobarg, J., Franchini, K.G., Targeting to C-terminal myosin heavy chain may explain mechanotransduction involving focal adhesion kinase in cardiomyocytes (2005) Circ Res, 96, pp. 73-81
dc.descriptionLietha, D., Cai, X., Ceccarelli, D.F., Li, Y., Schaller, M.D., Eck, M.J., Structural basis for the autoinhibition of focal adhesion kinase (2007) Cell, 129, pp. 1177-1187
dc.descriptionCalalb, M.B., Polte, T.R., Hanks, S.K., Tyrosine phosphorylation of focal adhesion kinase at sites in the catalytic domain regulates kinase activity: A role for Src family kinases (1995) Mol Cell Biol, 15, pp. 954-963
dc.descriptionHanks, S.K., Ryzhova, L., Shin, N.Y., Brabek, J., Focal adhesion kinase signaling activities and their implications in the control of cell survival and motility (2003) Front Biosci, 8, pp. d982-d996
dc.descriptionYu, D.H., Qu, C.K., Henegariu, O., Lu, X., Feng, G.S., Protein-tyrosine phos-phatase Shp-2 regulates cell spreading, migration, and focal adhesion (1998) J Biol Chem, 273, pp. 21125-21131
dc.descriptionManes, S., Mira, E., Gomez-Mouton, C., Zhao, Z.J., Lacalle, R.A., Martinez, A.C., Concerted activity of tyrosine phosphatase SHP-2 and focal adhesion kinase in regulation of cell motility (1999) Mol Cell Biol, 19, pp. 3125-3135
dc.descriptionVon Wichert, G., Haimovich, B., Feng, G.S., Sheetz, M.P., Force-dependent integrin-cytoskeleton linkage formation requires downregulation of focal complex dynamics by Shp2 (2003) EMBO J, 22, pp. 5023-5035
dc.descriptionRafiq, K., Kolpakov, M.A., Abdelfettah, M., Streblow, D.N., Hassid, A., Dell'italia, L.J., Sabri, A., Role of protein-tyrosine phosphatase SHP2 in focal adhesion kinase down-regulation during neutrophil cathepsin G-induced cardiomyo-cytes anoikis (2006) J Biol Chem, 281, pp. 19781-19792
dc.descriptionNeel, B.G., Gu, H., Pao, L., The 'Shp'ing news: SH2 domain-containing tyrosine phosphatases in cell signaling (2003) Trends Biochem Sci, 28, pp. 284-293
dc.descriptionShao, W., Orlando, R.C., Awayda, M.S., Bisphosphonates stimulate an endogenous nonselective cation channel in Xenopus oocytes: Potential mechanism of action (2005) Am J Physiol Cell Physiol, 289, pp. C248-C256
dc.descriptionOh, E.S., Gu, H., Saxton, T.M., Timms, J.F., Hausdorff, S., Frevert, E.U., Kahn, B.B., Thomas, S.M., Regulation of early events in integrin signaling by protein tyrosine phosphatase SHP-2 (1999) Mol Cell Biol, 19, pp. 3205-3215
dc.descriptionZhang, S.Q., Yang, W., Kontaridis, M.I., Bivona, T.G., Wen, G., Araki, T., Luo, J., Neel, B.G., Shp2 regulates SRC family kinase activity and Ras/Erk activation by controlling Csk recruitment (2004) Mol Cell, 13, pp. 341-355
dc.descriptionHeidkamp, M.C., Bayer, A.L., Kalina, J.A., Eble, D.M., Samarel, A.M., GFP-FRNK disrupts focal adhesions and induces anoikis in neonatal rat ventricular myocytes (2002) Circ Res, 90, pp. 1282-1289
dc.descriptionXu, F., Zhao, R., Peng, Y., Guerrah, A., Zhao, Z.J., Association of tyrosine phosphatase SHP-2 with F-actin at low cell densities (2001) J Biol Chem, 276, pp. 29479-29484
dc.descriptionSchoenwaelder, S.M., Petch, L.A., Williamson, D., Shen, R., Feng, G.S., Burridge, K., The protein tyrosine phosphatase Shp-2 regulates RhoA activity (2000) Curr Biol, 10, pp. 1523-1526
dc.descriptionCobb, B.S., Schaller, M.D., Leu, T.H., Parsons, J.T., Stable association of pp60src and pp59fyn with the focal adhesion-associated protein tyrosine kinase, pp125FAK (1994) Mol Cell Biol, 14, pp. 147-155
dc.descriptionAraki, T., Nawa, H., Neel, B.G., Tyrosyl phosphorylation of Shp2 is required for normal ERK activation in response to some, but not all, growth factors (2003) J Biol Chem, 278, pp. 41677-41684
dc.descriptionZito, C.I., Qin, H., Blenis, J., Bennett, A.M., SHP-2 regulates cell growth by controlling the mTOR/S6 kinase 1 pathway (2007) J Biol Chem, 282, pp. 6946-6953
dc.descriptionManning, B.D., Tee, A.R., Logsdon, M.N., Blenis, J., Cantley, L.C., Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway (2002) Mol Cell, 10, pp. 151-162
dc.descriptionGan, B., Yoo, Y., Guan, J.L., Association of focal adhesion kinase with tuberous sclerosis complex 2 in the regulation of s6 kinase activation and cell growth (2006) J Biol Chem, 281, pp. 37321-37329
dc.descriptionCrackower, M.A., Oudit, G.Y., Kozieradzki, I., Sarao, R., Sun, H., Sasaki, T., Hirsch, E., Penninger, J.M., Regulation of myocardial contractility and cell size by distinct PI3K-PTEN signaling pathways (2002) Cell, 110, pp. 737-749
dc.descriptionShioi, T., McMullen, J.R., Kang, P.M., Douglas, P.S., Obata, T., Franke, T.F., Cantley, L.C., Izumo, S., Akt/protein kinase B promotes organ growth in transgenic mice (2002) Mol Cell Biol, 22, pp. 2799-2809
dc.descriptionShioi, T., McMullen, J.R., Tarnavski, O., Converso, K., Sherwood, M.C., Manning, W.J., Izumo, S., Rapamycin attenuates load-induced cardiac hypertrophy in mice (2003) Circulation, 107, pp. 1664-1670
dc.descriptionCondorelli, G., Drusco, A., Stassi, G., Bellacosa, A., Roncarati, R., Iaccarino, G., Russo, M.A., Ross Jr.J, Akt induces enhanced myocardial contractility and cell size in vivo in transgenic mice (2002) Proc Natl Acad Sci U S A, 99, pp. 12333-12338
dc.descriptionMa, L., Chen, Z., Erdjument-Bromage, H., Tempst, P., Pandolfi, P.P., Phosphor-ylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis (2005) Cell, 121, pp. 179-193
dc.descriptionKontaridis, M.I., Yang, W., Bence, K.K., Cullen, D., Wang, B., Bodyak, N., Ke, Q., Neel, B.G., Deletion of Ptpn11 (Shp2) in cardiomyocytes causes dilated cardiomyopathy via effects on the extracellular signal-regulated kinase/mitogen-activated protein kinase and RhoA signaling pathways (2008) Circulation, 117, pp. 1423-1435
dc.descriptionWoywodt, A., Welzel, J., Haase, H., Duerholz, A., Wiegand, U., Potratz, J., Sheikhzadeh, A., Cardiomyopathic lentiginosis/LEOPARD syndrome presenting as sudden cardiac arrest (1998) Chest, 113, pp. 1415-1417
dc.descriptionTartaglia, M., Gelb, B.D., Noonan syndrome and related disorders: Genetics and pathogenesis (2005) Annu Rev Genomics Hum Genet, 6, pp. 45-68
dc.descriptionAraki, T., Mohi, M.G., Ismat, F.A., Bronson, R.T., Williams, I.R., Kutok, J.L., Yang, W., Neel, B.G., Mouse model of Noonan syndrome reveals cell type-and gene dosage-dependent effects of Ptpn11 mutation (2004) Nat Med, 10, pp. 849-857
dc.languageen
dc.publisher
dc.relationCirculation Research
dc.rightsfechado
dc.sourceScopus
dc.titleShp2 Negatively Regulates Growth In Cardiomyocytes By Controlling Focal Adhesion Kinase/src And Mtor Pathways
dc.typeArtículos de revistas


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