AD-LIKE TAU-PHOSPHORYLATION IN HUMAN NEUROBLASTOMA-CELLS FOLLOWING PKC HYPERACTIVATION IS MEDIATED BY MAP KINASE

SH-SY-5Y human neuroblastoma cells were treated with the phorbol ester TPA and the MAP kinase kinase inhibitors PD98059. Microdensitometric analyses revealed that TPA treatment induced 60% and 46% increases in immunoreactivity towards monoclonal antibodies (AT8 and PHF-1, respect ively; p=0.0005) that recognize tau epitopes common to paired helical filaments. These increases were attenuated by the simultaneous treatme nt with PD98059. Steady-state AT-8 and PHF-1 immunoreactivity were not inhibited by PD98059. These analyses corroborate studies from other l aboratories that indicate that MAP kinase may not normally confer AD-l ike immunoreactivity to tau within intact cells, but demonstrate that hyperactivation of upstream kinase(s) may recruit otherwise benign kin ases to hyperphosphorylate tau. These findings further implicate the p otential involvement of hyperactivation of signal transduction pathway s in the early events that propagate PHF formation.