Wortmannin and Its Structural Analogue Demethoxyviridin Inhibit Stimulated Phospholipase A
Activity in Swiss 3T3 Cells
WORTMANNIN IS NOT A SPECIFIC INHIBITOR OF PHOSPHATIDYLINOSITOL 3-KINASE (*)
- § To whom correspondence should be addressed: Institute for Cancer Studies, University of Birmingham, P. O. Box 363, Birmingham B15 2TT, UK.
Abstract
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 A
activity by both wortmannin and DMV with an IC
(2 nM) which is slightly more potent than the inhibition of insulin-stimulated phosphatidylinositol 3,4,5-trisphosphate generation
in these cells (
10 nM). While it has not been possible to fully block in vitro phospholipase A
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.
Footnotes
-
↵* This work was supported by grants from the Wellcome Trust, the Medical Research Council UK and the Cancer Research Campaign. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
-
↵1 The abbreviations used are:
- DMV
-
demethoxyviridin
- PLA
-
phospholipase A
- PI 3-kinase
-
phosphatidylinositol 3-kinase
- PLC
-
phospholipase C
- PLD
-
phospholipase D
- PIP
-
phosphatidylinositol 4,5-bisphosphate
- PIP
-
phosphatidylinositol 3,4,5-trisphosphate
- HPLC
-
high performance liquid chromatography.
-
- Received July 10, 1995.
- Revision received August 30, 1995.
- © 1995 by The American Society for Biochemistry and Molecular Biology, Inc.
