Inhibition of protein kinases by balanol: specificity within the serine/threonine protein kinase subfamily.

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.