Activation of mitogen-activated protein (MAP) kinase by a MAP kinase-kinase.

Previously it has been shown that acute 12-0-tetradecanoylphorbol-13-acetate treatment of intact US37 cells results in activation of mitogen-activated protein (MAP) kinase and a MAP kinase activator.MAP kinase activator induces phosphorylation of MAP kinase on tyrosine and threonine residues, thereby activating MAP kinase.Here, experiments with the irreversible kinase inhibitor, 6'-p-fluorosulfonylbenzoyladenosine (FSBA), show that MAP kinase activator is in fact a MAP kinase-kinase.Treatment of MAP kinase activator with FSBA results in complete inactivation.This inactivation is prevented by a 10-fold excess of ATP.Inactivation of MAP kinase by FSBA does not affect the extent of threonineltyrosine phosphorylation induced by MAP kinase-kinase.