Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Wortmannin, a Potent and Selective Inhibitor of Phosphatidylinositol-3-kinase

Wortmannin, a Potent and Selective Inhibitor of Phosphatidylinositol-3-kinase 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 n M . 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 µ M . 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. 1 Work in the laboratories of G.P., R.A., C.A. and L.Z. supported by NCI Grant CA52995. 2 To whom requests for reprints should be addressed, at Arizona Cancer Center, University of Arizona, 1515 North Campbell Avenue, Tucson, AZ 85724 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Cancer Research American Association of Cancer Research

Wortmannin, a Potent and Selective Inhibitor of Phosphatidylinositol-3-kinase

Wortmannin, a Potent and Selective Inhibitor of Phosphatidylinositol-3-kinase

Cancer Research , Volume 54 (9): 2419 – May 1, 1994

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 n M . 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 µ M . 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. 1 Work in the laboratories of G.P., R.A., C.A. and L.Z. supported by NCI Grant CA52995. 2 To whom requests for reprints should be addressed, at Arizona Cancer Center, University of Arizona, 1515 North Campbell Avenue, Tucson, AZ 85724

Loading next page...
 
/lp/american-association-of-cancer-research/wortmannin-a-potent-and-selective-inhibitor-of-phosphatidylinositol-3-ZatVCKPjVk

References

References for this paper are not available at this time. We will be adding them shortly, thank you for your patience.

Publisher
American Association of Cancer Research
Copyright
Copyright © 1994 by the American Association for Cancer Research.
ISSN
0008-5472
Publisher site

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 n M . 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 µ M . 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. 1 Work in the laboratories of G.P., R.A., C.A. and L.Z. supported by NCI Grant CA52995. 2 To whom requests for reprints should be addressed, at Arizona Cancer Center, University of Arizona, 1515 North Campbell Avenue, Tucson, AZ 85724

Journal

Cancer ResearchAmerican Association of Cancer Research

Published: May 1, 1994

There are no references for this article.