M. Lesort et al., Insulin transiently increases tau phosphorylation: Involvement of glycogensynthase kinase-3 beta and Fyn tyrosine kinase, J NEUROCHEM, 72(2), 1999, pp. 576-584
The modulation of tau phosphorylation in response to insulin was examined i
n human neuroblastoma SH-SY5Y cells. Insulin treatment resulted in a transi
ent increase in tau phosphorylation followed by a decrease in tau phosphory
lation that correlated directly with a sequential activation and deactivati
on of glycogen synthase kinase-3 beta (GSK-3 beta). The insulin-induced inc
rease in tau phosphorylation and concurrent activation of GSK-3 beta was ra
pid (<2 min) and transient, and was associated with increased tyrosine phos
phorylation of GSK-3 beta. The increase in GSK-3 beta tyrosine phosphorylat
ion corresponded directly to an increase in the association of Fyn tyrosine
kinase with GSK-3 beta, and Fyn immunoprecipitated from cells treated with
insulin for 1 min phosphorylated GSK-3 beta to a significantly greater ext
ent than Fyn immunoprecipitated from control cells. Subsequent to the incre
ase in GSK-3 beta activation and tau phosphorylation, treatment of cells wi
th insulin for 60 min resulted in a dephosphorylation of tau and a decrease
in GSK-3 beta activity. Thus, insulin rapidly and transiently activated GS
K-3 beta and modulated tau phosphorylation, alterations that may contribute
to neuronal plasticity.