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.
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