Phorbol ester stimulates the synthesis of sphingomyelin in NIH 3T3 cells. A diminished response in cells transformed with human A-raf carrying retrovirus.
The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) stimulated the synthesis of sphingomyelin (CerPCho) from a [14C]choline-labelled phosphatidylcholine (PtdCho) pool in NIH 3T3 cells. Maximal stimulation (68%) of CerPCho synthesis, accompanied by an increase (38%) in its cellular content, required only 2 nM TPA. Higher concentrations of TPA (2-100 nM) had progressively less effect on CerPCho synthesis which correlated with increased hydrolysis of precursor PtdCho. In cells transformed with human or mouse A-raf carrying retroviruses TPA-stimulated PtdCho hydrolysis, but not CerPCho synthesis, suggesting independent regulation of these processes by the TPA-stimulated signal transduction system.
Kiss
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Z
Division of Cancer Biology and Diagnosis, National Cancer Institute, Bethesda, MD 20892.
Rapp
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UR
Anderson
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WB
D000818:Animals; D002460:Cell Line; D002472:Cell Transformation, Viral; D004789:Enzyme Activation / Q000187:drug effects; D051379:Mice; D009857:Oncogenes; D011493:Protein Kinase C / Q000502:physiology; D013109:Sphingomyelins / Q000096:biosynthesis*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D013109:Sphingomyelins; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate