DOI: 10.1152/ajpheart.2000.279.6.h2916. Striated muscle-specific β<sub>1D</sub>-integrin and FAK are involved in cardiac myocyte hypertrophic response pathway

Striated muscle-specific β1D-integrin and FAK are involved in cardiac myocyte hypertrophic response pathway

10.1152/ajpheart.2000.279.6.h2916

Crossref journal-article

American Physiological Society

American Journal of Physiology-Heart and Circulatory Physiology (24)

Abstract

Alterations in the extracellular matrix occur during the cardiac hypertrophic process. Because integrins mediate cell-matrix adhesion and β1D-integrin (β1D) is expressed exclusively in cardiac and skeletal muscle, we hypothesized that β1D and focal adhesion kinase (FAK), a proximal integrin-signaling molecule, are involved in cardiac growth. With the use of cultured ventricular myocytes and myocardial tissue, we found the following: 1) β1D protein expression was upregulated perinatally; 2) α1-adrenergic stimulation of cardiac myocytes increased β1D protein levels 350% and altered its cellular distribution; 3) adenovirally mediated overexpression of β1D stimulated cellular reorganization, increased cell size by 250%, and induced molecular markers of the hypertrophic response; and 4) overexpression of free β1D cytoplasmic domains inhibited α1-adrenergic cellular organization and atrial natriuretic factor (ANF) expression. Additionally, FAK was linked to the hypertrophic response as follows: 1) coimmunoprecipitation of β1D and FAK was detected; 2) FAK overexpression induced ANF-luciferase; 3) rapid and sustained phosphorylation of FAK was induced by α1-adrenergic stimulation; and 4) blunting of the α1-adrenergically modulated hypertrophic response was caused by FAK mutants, which alter Grb2 or Src binding, as well as by FAK-related nonkinase, a dominant interfering FAK mutant. We conclude that β1D and FAK are both components of the hypertrophic response pathway of cardiac myocytes.

Bibliography

Pham, C. G., Harpf, A. E., Keller, R. S., Vu, H. T., Shai, S.-Y., Loftus, J. C., & Ross, R. S. (2000). Striated muscle-specific Î²1D-integrin and FAK are involved in cardiac myocyte hypertrophic response pathway. American Journal of Physiology-Heart and Circulatory Physiology, 279(6), H2916âH2926.

Authors 7

Can G. Pham (first)
Alice E. Harpf (additional)
Rebecca S. Keller (additional)
Hoa T. Vu (additional)
Shaw-Yung Shai (additional)
Joseph C. Loftus (additional)
Robert S. Ross (additional)

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Dates

Type	When
Created	7 years, 8 months ago (Dec. 22, 2017, 4:13 a.m.)
Deposited	3 years ago (Aug. 10, 2022, 9:52 p.m.)
Indexed	2 months ago (June 25, 2025, 1:12 p.m.)
Issued	24 years, 8 months ago (Dec. 1, 2000)
Published	24 years, 8 months ago (Dec. 1, 2000)
Published Print	24 years, 8 months ago (Dec. 1, 2000)

Funders 0

None

BibTeX

@article{Pham_2000, title={Striated muscle-specific β1D-integrin and FAK are involved in cardiac myocyte hypertrophic response pathway}, volume={279}, ISSN={1522-1539}, url={http://dx.doi.org/10.1152/ajpheart.2000.279.6.h2916}, DOI={10.1152/ajpheart.2000.279.6.h2916}, number={6}, journal={American Journal of Physiology-Heart and Circulatory Physiology}, publisher={American Physiological Society}, author={Pham, Can G. and Harpf, Alice E. and Keller, Rebecca S. and Vu, Hoa T. and Shai, Shaw-Yung and Loftus, Joseph C. and Ross, Robert S.}, year={2000}, month=dec, pages={H2916–H2926} }

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  "abstract": "<jats:p>Alterations in the extracellular matrix occur during the cardiac hypertrophic process. Because integrins mediate cell-matrix adhesion and \u03b2<jats:sub>1D</jats:sub>-integrin (\u03b21D) is expressed exclusively in cardiac and skeletal muscle, we hypothesized that \u03b21D and focal adhesion kinase (FAK), a proximal integrin-signaling molecule, are involved in cardiac growth. With the use of cultured ventricular myocytes and myocardial tissue, we found the following: 1) \u03b21D protein expression was upregulated perinatally; 2) \u03b1<jats:sub>1</jats:sub>-adrenergic stimulation of cardiac myocytes increased \u03b21D protein levels 350% and altered its cellular distribution; 3) adenovirally mediated overexpression of \u03b21D stimulated cellular reorganization, increased cell size by 250%, and induced molecular markers of the hypertrophic response; and 4) overexpression of free \u03b21D cytoplasmic domains inhibited \u03b1<jats:sub>1</jats:sub>-adrenergic cellular organization and atrial natriuretic factor (ANF) expression. Additionally, FAK was linked to the hypertrophic response as follows: 1) coimmunoprecipitation of \u03b21D and FAK was detected; 2) FAK overexpression induced ANF-luciferase; 3) rapid and sustained phosphorylation of FAK was induced by \u03b1<jats:sub>1</jats:sub>-adrenergic stimulation; and 4) blunting of the \u03b1<jats:sub>1</jats:sub>-adrenergically modulated hypertrophic response was caused by FAK mutants, which alter Grb2 or Src binding, as well as by FAK-related nonkinase, a dominant interfering FAK mutant. We conclude that \u03b21D and FAK are both components of the hypertrophic response pathway of cardiac myocytes.</jats:p>",
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