OKADAIC ACID, A SERINE/THREONINE PHOSPHATASE INHIBITOR, INDUCES TYROSINE DEPHOSPHORYLATION INACTIVATION OF PROTEIN-KINASE F-A/GSK-3-ALPHA IN A431 CELLS

[[abstract]]The signal transduction mechanism of protein kinase F-A/GSK-3 alpha by tyrosine phosphorylation in A431 cells was investigated. Kinase F(A)GSK-3 alpha was found to exist in a highly tyrosine-phosphorylated/activated state in resting cells but could be tyrosine-dephosphorylated and inactivated down to less than 15% of control values in a concentration-dependent manner by 50-400 nM okadaic acid (a specific inhibitor of protein phosphatase types 1 and 2A), as demonstrated by metabolic P-32 labeling the cells, followed by immunoprecipitation and two dimensional phosphoamino acid analysis and by immunodetection in an anti-kinase F-A/GSK-3 alpha immunoprecipitate kinase assay. Taken together, the results provide initial evidence that serine/threonine phosphatase(s) may play a role involved in the modulation of kinase F-A/GSK-3 alpha activity in cells, suggesting an involvement of serine/ threonine dephosphorylation in the modulation of tyrosine phosphorylation and activation of protein kinase F-A/GSK-3 alpha, representing a new mode of signal transduction pathway for the regulation of this multisubstrate protein kinase in cells.[[fileno]]2050116010024[[department]]生科