Ras/MAP kinase pathway is associated with the control of myotube formation but not myofibril assembly in quail myoblasts transformed with Rous sarcoma virus.
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 (P13-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 P13-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.
Hirayama
E
E
Institute of Molecular and Cellular Biology for Pharmaceutical Sciences, Kyoto Pharmaceutical University, Japan.
Isobe
A
A
Kajihara
Y
Y
Kim
J
J
Hamaguchi
M
M
D000818:Animals; D001358:Avian Sarcoma Viruses; D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D005786:Gene Expression Regulation; D016391:Genes, src; D020935:MAP Kinase Signaling System / Q000502:physiology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000166:cytology* / Q000201:enzymology*; D009210:Myofibrils / Q000201:enzymology*; D011784:Quail; D013696:Temperature; D014162:Transfection; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*
D004791:Enzyme Inhibitors; D005419:Flavonoids; D020929:Mitogen-Activated Protein Kinase Kinases; D018631:ras Proteins; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one