Abstract
Phosphatidylinositol-3-kinase is an important enzyme for intracellular signaling. The microbial product worthmannin and some of its analogues have been shown to be potent inhibitors of phosphatidylinositol-3-kinase. The 50% inhibitory concentration for inhibition by wortmannin is 2 to 4 nm. Kinetic analysis demonstrates that wortmannin is a noncompetitive, irreversible inhibitor of phosphatidylinositol-3-kinase, with inactivation being both time- and concentration-dependent. Wortmannin has previously been reported to be an inhibitor of myosin light chain kinase but with an inhibitory concentration of 0.2 µm. Wortmannin was found not to be an inhibitor of phosphatidylinositol-4-kinase, protein kinase C, or protein tyrosine kinase. Wortmannin inhibited the formation of phosphatidylinositol-3-phosphates in intact cells. The results of the study suggest that wortmannin and its analogues may have utility as pharmacological probes for studying the actions of phosphatidylinositol-3-kinase.
Footnotes
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↵1 Work in the laboratories of G.P., R.A., C.A. and L.Z. supported by NCI Grant CA52995.
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↵2 To whom requests for reprints should be addressed, at Arizona Cancer Center, University of Arizona, 1515 North Campbell Avenue, Tucson, AZ 85724
- Received December 3, 1993.
- Accepted February 28, 1994.
- ©1994 American Association for Cancer Research.
Volume 54, Issue 9
