RhoA controls myoblast survival by inducing the phosphatidylinositol 3-kinase-Akt signaling pathway.
The small GTPase RhoA regulates the expression of the myogenic transcription factor, MyoD, and the transcription of muscle-specific genes. We report that RhoA also affects the survival of differentiating myoblasts. Two signaling pathways, extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3-kinase (PI3-K)-Akt, are involved in myoblast survival. Here, we show that inhibition of RhoA prevents the phosphorylation of Akt, but does not affect the phosphorylation of ERK. Constitutive expression of an active form of Akt prevents apoptosis in myoblasts treated with the Rho inhibitor C3-transferase. These results indicate that RhoA functions to prevent myoblast death by inducing the PI3-K-Akt pathway.
Reuveny
Mickol
M
Department of Biochemistry, Faculty of Medicine, Rappaport Institute for Research in the Medical Sciences, Technion-Israel Institute of Technology, P.O. Box 9649, Haifa 31096, Israel.
Heller
Hanna
H
Bengal
Eyal
E
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D002470:Cell Survival; D002999:Clone Cells; D004790:Enzyme Induction; D032446:Myoblasts / Q000166:cytology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D011994:Recombinant Proteins; D020742:rhoA GTP-Binding Protein