Focal adhesion kinase is activated and mediates the early hypertrophic response to stretch in cardiac myocytes

dc.creatorTorsoni, AS
dc.creatorConstancio, SS
dc.creatorNadruz, W
dc.creatorHanks, SK
dc.creatorFranchini, KG
dc.date2003
dc.date45839
dc.date2014-11-18T07:08:36Z
dc.date2015-11-26T16:52:20Z
dc.date2014-11-18T07:08:36Z
dc.date2015-11-26T16:52:20Z
dc.date.accessioned2018-03-28T23:39:15Z
dc.date.available2018-03-28T23:39:15Z
dc.identifierCirculation Research. Lippincott Williams & Wilkins, v. 93, n. 2, n. 140, n. 147, 2003.
dc.identifier0009-7330
dc.identifierWOS:000184346500009
dc.identifier10.1161/01.RES.0000081595.25297.1B
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/67356
dc.identifierhttp://www.repositorio.unicamp.br/handle/REPOSIP/67356
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/67356
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1276250
dc.descriptionPreviously we reported that the rapid activation of the Fak/Src multicomponent signaling complex mediates load-induced activation of growth and survival signaling pathways in adult rat heart. In this study, we report that 5% to 20% (10-minute) cyclic stretch (1 Hz) of neonatal rat ventricular myocytes (NRVMs) was paralleled by increases of Fak phosphorylation at Tyr-397 (from 1.5- to 2.8-fold), as detected by anti-Fak-pY(397) phosphospecific antibody. Moreover, 15% cyclic stretch lasting from 10 to 120 minutes increased Fak phosphorylation at Tyr-397 by 2.5- to 3.5-fold. This activation was accompanied by a dramatic change in Fak localization in NRVMs from densely concentrated in the perinuclear regions in nonstretched cells to aggregates regularly distributed along the myofilaments in stretched cells. Furthermore, a 4-hour cyclic stretch enhanced the activity of an atrial natriuretic factor (ANF) promoter-luciferase reporter gene by 2.7-fold. Disrupting endogenous Fak/Src signaling either by expression of a dominant-negative Fak mutant with phenylalanine substituted for Tyr-397 or by treatment with a c-Src pharmacological inhibitor (PP-2) markedly attenuated stretch-induced Fak activation and clustering at myofilaments and inhibited stretch-induced ANF gene activation. On the other hand, overexpression of wild-type Fak potentiated the stretch-induced Fak phosphorylation but did not enhance either baseline or stretch-induced ANF promoter-luciferase reporter gene activity compared with the responses of nontransfected NRVMs. These findings identify Fak as an important element in the early responses induced by stretch in cardiac myocytes, indicating that it may coordinate the cellular signaling machinery that controls gene expression program associated with load-induced cardiac myocyte hypertrophy.
dc.descriptionO TEXTO COMPLETO DESTE ARTIGO, ESTARÁ DISPONÍVEL À PARTIR DE FEVEREIRO DE 2015.
dc.description93
dc.description2
dc.description140
dc.description147
dc.languageen
dc.publisherLippincott Williams & Wilkins
dc.publisherPhiladelphia
dc.publisherEUA
dc.relationCirculation Research
dc.relationCirc.Res.
dc.rightsembargo
dc.sourceWeb of Science
dc.subjectfocal adhesion kinase
dc.subjectmechanotransduction
dc.subjectcell signaling
dc.subjecthypertrophy
dc.subjectRat Ventricular Cardiomyocytes
dc.subjectSrc Family Kinases
dc.subjectTyrosine Phosphorylation
dc.subjectPressure-overload
dc.subjectComplex-formation
dc.subjectCell-cycle
dc.subjectExpression
dc.subjectIntegrins
dc.subjectFak
dc.subjectMyocardium
dc.titleFocal adhesion kinase is activated and mediates the early hypertrophic response to stretch in cardiac myocytes
dc.typeArtículos de revistas


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