Differential modulation of protein kinase C by bryostatin 1 and phorbol ester.

Abstract

Bryostatin 1, a macrocyclic lactone, activated protein kinase C purified from mouse brain in a dose-dependent fashion to the same degree as phorbol 12-myristate 13-acetate (PMA). There was no significant difference in calcium and phosphatidylserine requirements for activation of protein kinase C between bryostatin 1 and PMA. We also found no significant difference in the inhibitory effect between staurosporine and H-7 known to be potent inhibitors of protein kinase C. These data suggest that bryostatin 1 and PMA activate protein kinase C in a similar way. We found, however, that negative modulation of protein kinase C with bryostatin 1 was weaker than that with PMA. The reason of this difference was unclear. It may possibly suggest that there is some difference in configuration of protein kinase C after binding between these activators.