Sphingosine blocks both membrane fusion and calmodulin-dependent phosphorylation of the 100-kDa protein of chick embryonic myoblasts.
Sphingosine, a potent inhibitor of protein kinase C, was found to block membrane fusion of chick embryonic myoblasts in culture. This effect was dose-dependent and could be reversed upon removal of the drug. Treatment with 12-O-tetradecanoylphorbol 13-acetate, which is a powerful activator of protein kinase C and capable of preventing myoblast fusion, further potentiated the inhibitory effect of sphingosine. Thus, the sphingosine-mediated inhibition of myoblast fusion appears to be independent of protein kinase C. Sphingosine also decreased the phosphorylation state of the 100-kDa protein when given to the cell extracts, and this inhibition was competitive with calmodulin. Thus, sphingosine seems to act as a calmodulin antagonist. These results suggest that the sphingosine-mediated inhibition of myoblast fusion may be associated with the inhibitory effect of the drug against the calmodulin-dependent phosphorylation of the 100-kDa protein.
Kim
H S
HS
Department of Molecular Biology and SRC for Cell Differentiation, College of Natural Sciences, Seoul National University, Korea.
Lee
I H
IH
Jeon
Y J
YJ
Chung
C H
CH
Ha
D B
DB
D000818:Animals; D002147:Calmodulin / Q000502:physiology; D002642:Chick Embryo; D004533:Egtazic Acid / Q000494:pharmacology; D008561:Membrane Fusion / Q000187:drug effects*; D009124:Muscle Proteins / Q000378:metabolism*; D009132:Muscles / Q000166:cytology*; D010766:Phosphorylation / Q000187:drug effects; D013110:Sphingosine / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014268:Trifluoperazine / Q000494:pharmacology
D002147:Calmodulin; D009124:Muscle Proteins; D014268:Trifluoperazine; D004533:Egtazic Acid; D013110:Sphingosine; D013755:Tetradecanoylphorbol Acetate