Abstract
Balanol is a potent inhibitor of cyclic AMP-dependent protein kinase and protein kinase C, acting competitively with ATP with an affinity 3000 times that of ATP. We tested the capacity of balanol to inhibit representative serine- and threonine-specific protein kinases from the protein kinase subfamily that shares a common conserved catalytic core with cyclic AMP-dependent protein kinase. Balanol’s pattern of interactions indicates considerable diversity of the ATP/balanol-binding sites of protein kinases within familial groups and even among isoforms of the same kinase. We propose that balanol is a protean structure that may be modified to produce selective, high-affinity inhibitors and probes of the ATP-binding sites of serine/threonine protein kinases.
Footnotes
- Received February 11, 1999.
- Accepted April 8, 1999.
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Send reprint requests to: Laurence L. Brunton, Ph.D., Department of Pharmacology 0636, University of California San Diego, School of Medicine, La Jolla, CA 92093. E-mail:lbrunton{at}ucsd.edu
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This work was supported by National Institutes of Health Grants HL41307 and GM19301, a Lucille P. Markey fellowship, and an NSF predoctoral fellowship (to T.C.D.).
- The American Society for Pharmacology and Experimental Therapeutics
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