Inhibition of CDP-DG: inositol transferase by inostamycin.
Inostamycin, a novel microbial secondary metabolite, inhibited [3H]inositol and 32P1 incorporation into phosphatidylinositol (PtdIns) induced by epidermal growth factor (EGF) in cultured A431 cells, the IC50 being 0.5 micrograms/ml, without inhibiting macromolecular synthesis. The drug inhibited cellular inositol phosphate formation only when it was added at the same time as labeled inositol. It was found to inhibit in vitro CDP-DG:inositol transferase activity of the A431 cell membrane, the IC50 being about 0.02 micrograms/ml. It did not inhibit tyrosine kinase, PtdIns phospholipase C, or PtdIns kinase. Therefore, inhibition of PtdIns turnover by inostamycin must be due to the inhibition of CDP-DG:inositol transferase. Thus, inostamycin is a novel inhibitor of CDP-DG:inositol transferase.
Imoto
M
M
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Kanagawa.
Taniguchi
Y
Y
Umezawa
K
K
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D051607:CDP-Diacylglycerol-Inositol 3-Phosphatidyltransferase; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005663:Furans / Q000494:pharmacology; D007294:Inositol / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D010770:Phosphotransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017855:Transferases (Other Substituted Phosphate Groups); D010738:Type C Phospholipases / Q000378:metabolism
D000900:Anti-Bacterial Agents; D005663:Furans; D010716:Phosphatidylinositols; D010743:Phospholipids; C071861:inostamycin; D007294:Inositol; D004815:Epidermal Growth Factor; D010770:Phosphotransferases; D017855:Transferases (Other Substituted Phosphate Groups); D051607:CDP-Diacylglycerol-Inositol 3-Phosphatidyltransferase; D010738:Type C Phospholipases