Involvement of protein kinase C in the regulation of glycolipid sulfotransferase activity levels in renal cell carcinoma cells.
Accumulation of sulfolipids associated with elevated levels of glycolipid sulfotransferase activities has previously been demonstrated in renal cell carcinoma cells. To investigate the role of protein kinase C in the synthesis of sulfolipids, the effects of 12-O-tetradecanoylphorbol-13-acetate and protein kinase C inhibitors on glycolipid sulfotransferase activity levels were examined in a human renal cell carcinoma cell line, SMKT-R3. Continuous treatment of the cells with 12-O-tetradecanoylphorbol-13-acetate caused a dose- and time-dependent reduction of the sulfotransferase activity levels. Similarly, protein kinase C inhibitors, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride and staurosporine, reduced the enzyme activities in a dose-dependent manner. These observations suggest that the glycolipid sulfotransferase activity levels are regulated by protein kinase C in SMKT-R3 cells. Furthermore, long-term 12-O-tetradecanoylphorbol-13-acetate treatment resulted in a reduction of sulfolipid synthesis and a decrease of the expression of sulfolipids on the cell surface. Taken together, it is suggested that protein kinase C is involved in the synthesis of sulfolipids through the regulation of the glycolipid sulfotransferase activity levels in renal cell carcinoma cells.
Kobayashi
T
T
Biochemistry and Virology Laboratory, Hokkaido University School of Medicine, Sapporo, Japan.
Honke
K
K
Gasa
S
S
Sugiura
M
M
Miyazaki
T
T
Ishizuka
I
I
Makita
A
A
D002292:Carcinoma, Renal Cell / Q000201:enzymology*; D002553:Cerebroside-Sulfatase / Q000187:drug effects / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D015536:Down-Regulation; D006801:Humans; D007680:Kidney Neoplasms / Q000201:enzymology*; D008055:Lipids / Q000096:biosynthesis; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D015238:Sulfotransferases; D013466:Sulfurtransferases / Q000187:drug effects / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured
D008055:Lipids; C015518:sulfolipids; D003907:Dexamethasone; D003513:Cycloheximide; D011493:Protein Kinase C; D013466:Sulfurtransferases; D015238:Sulfotransferases; C020556:galactosylceramide sulfotransferase; D002553:Cerebroside-Sulfatase; D013755:Tetradecanoylphorbol Acetate