Striated muscle-specific beta(1D)-integrin and FAK are involved in cardiac myocyte hypertrophic response pathway

Am J Physiol Heart Circ Physiol. 2000 Dec;279(6):H2916-26. doi: 10.1152/ajpheart.2000.279.6.H2916.


Alterations in the extracellular matrix occur during the cardiac hypertrophic process. Because integrins mediate cell-matrix adhesion and beta(1D)-integrin (beta1D) is expressed exclusively in cardiac and skeletal muscle, we hypothesized that beta1D 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) beta1D protein expression was upregulated perinatally; 2) alpha(1)-adrenergic stimulation of cardiac myocytes increased beta1D protein levels 350% and altered its cellular distribution; 3) adenovirally mediated overexpression of beta1D stimulated cellular reorganization, increased cell size by 250%, and induced molecular markers of the hypertrophic response; and 4) overexpression of free beta1D cytoplasmic domains inhibited alpha(1)-adrenergic cellular organization and atrial natriuretic factor (ANF) expression. Additionally, FAK was linked to the hypertrophic response as follows: 1) coimmunoprecipitation of beta1D and FAK was detected; 2) FAK overexpression induced ANF-luciferase; 3) rapid and sustained phosphorylation of FAK was induced by alpha(1)-adrenergic stimulation; and 4) blunting of the alpha(1)-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 beta1D and FAK are both components of the hypertrophic response pathway of cardiac myocytes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Animals, Newborn
  • Antibodies
  • Atrial Natriuretic Factor / metabolism
  • Cardiomegaly / metabolism*
  • Cardiomegaly / pathology
  • Cardiotonic Agents / pharmacology
  • Cell Size / physiology
  • Cytoplasm / physiology
  • Extracellular Matrix / metabolism
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • Gene Expression Regulation, Developmental
  • Gene Expression Regulation, Enzymologic
  • Genes, Reporter
  • Heart Ventricles / enzymology
  • Heart Ventricles / pathology
  • Integrin beta1 / chemistry
  • Integrin beta1 / genetics*
  • Integrin beta1 / immunology
  • Molecular Sequence Data
  • Muscle Fibers, Skeletal / enzymology*
  • Muscle Fibers, Skeletal / pathology
  • Muscle, Skeletal / enzymology*
  • Myocardium / enzymology
  • Myocardium / pathology*
  • Phenylephrine / pharmacology
  • Phosphorylation
  • Protein Structure, Tertiary
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / physiology


  • Antibodies
  • Cardiotonic Agents
  • Integrin beta1
  • Phenylephrine
  • Atrial Natriuretic Factor
  • Protein-Tyrosine Kinases
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • Ptk2 protein, rat