Abstract
Tyrosine kinase activity of v-Src from Rous sarcoma virus (RSV) inhibits the differentiation of quail myoblasts. To clarify the inhibitory mechanism, we focused on the signaling pathways from v-Src. When the activation of the Ras/MAP (mitogen-activated protein) kinase pathway was inhibited by a dominant-negative mutant of Ras or PD98059, a specific inhibitor of p42 MAP kinase kinase, differentiation was restored; muscle specific proteins were expressed and myotubes formed even under active conditions of v-Src. Wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase (PI3-kinase), showed no effects on the inhibition by v-Src. These findings suggest that v-Src activates the Ras/MAP kinase signaling pathway, but not the PI3-kinase pathway, and inhibits the differentiation. However, the myotubes derived from the dominant-negative Ras did not form actin fibers, suggesting that myofibril assembly is regulated by other pathway(s) from v-Src.
