β-Integrin and PI 3-kinase regulate RhoA-dependent activation of skeletal α-actin promoter in myoblasts

Lei Wei, Wei Zhou, L. U. Wang, Robert J. Schwartz

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

RhoA GTPase, a regulator of actin cytoskeleton, is also involved in regulating c-fos gene expression through its effect on serum response factor (SRF) transcriptional activity. We have also shown that RhoA plays a critical role in myogenesis and regulates expression of SRF-dependent muscle genes, including skeletal α-actin. In the present study, we examined whether the RhoA signaling pathway cross talks with other myogenic signaling pathways to modulate skeletal α-actin promoter activity in myoblasts. We found that extracellular matrix proteins and the β1-integrin stimulated RhoA-dependent activation of the α-actin promoter. The muscle-specific isoform β(1D) selectively activated the α-actin promoter in concert with RhoA but inhibited the c-fos promoter. In addition, focal adhesion kinase (FAK) and phosphatidylinositol (PI) 3-kinase were required for full activation of the α-actin promoter by RhoA. Expression of a dominant negative mutant of FAK, application of wortmannin to cultured myoblasts, or expression of a dominant negative mutant of PI 3-kinase inhibited α-actin promoter activity induced by RhoA. These results suggest that RhoA, β1-integrin, FAK, and PI 3-kinase serve together as an important signaling network in regulating muscle gene expression.

Original languageEnglish (US)
Pages (from-to)H1736-H1743
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume278
Issue number6 47-6
DOIs
StatePublished - Jun 2000

Keywords

  • Focal adhesion kinase
  • RhoA signaling
  • β(1D)-integrin

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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