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Wortmannin and its structural analogue demethoxyviridin (DMV) have been reported to be specific inhibitors of phosphatidylinositol 3-kinase activity. Here we report that these compounds are not as selective as assumed and demonstrate inhibition of bombesin-stimulated phospholipase A2 activity by both wortmannin and DMV with an IC50 (2 nM) which is slightly more potent than the inhibition of insulin-stimulated phosphatidylinositol 3,4,5-trisphosphate generation in these cells (approximately 10nM). While it has not been possible to fully block in vitro phospholipase A2 activity with wortmannin, inhibition cannot be a consequence of inhibition of PI 3-kinase activity since bombesin fails to generate 3-phosphorylated lipids in the intact cell. Therefore, while wortmannin is indeed a PI 3-kinase inhibitor, it is not as specific as previously reported, and experimental conclusions based solely on its use should be treated with caution.

Original publication

DOI

10.1074/jbc.270.43.25352

Type

Journal article

Journal

J Biol Chem

Publication Date

27/10/1995

Volume

270

Pages

25352 - 25355

Keywords

3T3 Cells, Androstadienes, Androstenes, Animals, Bombesin, Dose-Response Relationship, Drug, Enzyme Activation, Mice, Phosphatidylinositol 3-Kinases, Phosphatidylinositol Phosphates, Phosphodiesterase Inhibitors, Phospholipase D, Phospholipases, Phospholipases A, Phospholipases A2, Phosphotransferases (Alcohol Group Acceptor), Type C Phospholipases, Wortmannin