DOI: 10.1161/01.res.0000081595.25297.1b. Focal Adhesion Kinase Is Activated and Mediates the Early Hypertrophic Response to Stretch in Cardiac Myocytes

Focal Adhesion Kinase Is Activated and Mediates the Early Hypertrophic Response to Stretch in Cardiac Myocytes

10.1161/01.res.0000081595.25297.1b

Crossref journal-article

Ovid Technologies (Wolters Kluwer Health)

Circulation Research (276)

Abstract

Previously 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.

Bibliography

Torsoni, A. S., Constancio, S. S., Nadruz, W., Hanks, S. K., & Franchini, K. G. (2003). Focal Adhesion Kinase Is Activated and Mediates the Early Hypertrophic Response to Stretch in Cardiac Myocytes. Circulation Research, 93(2), 140â147.

Authors 5

Adriana S. Torsoni (first)
Sabata S. Constancio (additional)
Wilson Nadruz (additional)
Steven K. Hanks (additional)
Kleber G. Franchini (additional)

References 37 Referenced 157

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Sugden PH, Clerk A. “Stress-responsive” mitogen-activated protein kinases (c-Jun N-terminal kinases and p38 mitogen-activated protein kinases) in the myocardium. Circ Res. 1998; 24: 345–352. / Circ Res (1998)
10.1074/jbc.270.47.28092
Eble DM Qi M Strait JB Samarel AM. Contraction-dependent hypertrophy of neonatal rat ventricular myocytes: potential role for focal adhesion kinase. In: Takeda N Dhalla NJ eds. The Hypertrophied Heart. Boston Mass: Kluwer; 2000: 91–107. (10.1007/978-1-4615-4423-4_8)

Dates

Type	When
Created	22 years, 2 months ago (June 16, 2003, 8:24 p.m.)
Deposited	1 year, 3 months ago (May 12, 2024, 2:31 p.m.)
Indexed	3 weeks ago (Aug. 6, 2025, 8:14 a.m.)
Issued	22 years, 1 month ago (July 25, 2003)
Published	22 years, 1 month ago (July 25, 2003)
Published Print	22 years, 1 month ago (July 25, 2003)

Funders 0

None

BibTeX

@article{Torsoni_2003, title={Focal Adhesion Kinase Is Activated and Mediates the Early Hypertrophic Response to Stretch in Cardiac Myocytes}, volume={93}, ISSN={1524-4571}, url={http://dx.doi.org/10.1161/01.res.0000081595.25297.1b}, DOI={10.1161/01.res.0000081595.25297.1b}, number={2}, journal={Circulation Research}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Torsoni, Adriana S. and Constancio, Sabata S. and Nadruz, Wilson and Hanks, Steven K. and Franchini, Kleber G.}, year={2003}, month=jul, pages={140–147} }

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