beta(1)-integrin and PI 3-kinase regulate RhoA-dependent activation of skeletal alpha-actin promoter in myoblasts.
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 alpha-actin. In the present study, we examined whether the RhoA signaling pathway cross talks with other myogenic signaling pathways to modulate skeletal alpha-actin promoter activity in myoblasts. We found that extracellular matrix proteins and the beta(1)-integrin stimulated RhoA-dependent activation of the alpha-actin promoter. The muscle-specific isoform beta(1D) selectively activated the alpha-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 alpha-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 alpha-actin promoter activity induced by RhoA. These results suggest that RhoA, beta(1)-integrin, FAK, and PI 3-kinase serve together as an important signaling network in regulating muscle gene expression.
Wei
L
L
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Zhou
W
W
Wang
L
L
Schwartz
R J
RJ
D000199:Actins / Q000235:genetics*; D000818:Animals; D002478:Cells, Cultured; D016326:Extracellular Matrix Proteins / Q000502:physiology; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019012:Integrin beta1 / Q000502:physiology*; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000502:physiology*; D020033:Protein Isoforms / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D020742:rhoA GTP-Binding Protein / Q000737:chemistry / Q000502:physiology*
D000199:Actins; D016326:Extracellular Matrix Proteins; D019012:Integrin beta1; D020033:Protein Isoforms; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496051:Ptk2 protein, mouse; D020742:rhoA GTP-Binding Protein