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 pr otein kinase C, acting competitively with ATP with an affinity 3000 times t hat of ATP. We tested the capacity of balanol to inhibit representative ser ine- and threonine-specific protein kinases from the protein kinase subfami ly that shares a common conserved catalytic core with cyclic AMP-dependent protein kinase. Balanol's pattern of interactions indicates considerable di versity 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-aff inity inhibitors and probes of the ATP-binding sites of serine/threonine pr otein kinases.