Effect of Blocking Tyrosine Kinase Src Expression on Protein Phosphatase 2A and Tau Phosphorylation

objective:The effect of tyrosine kinase Src on Tyrosine 307(Y307) phosphorylation and activity of protein phosphatase 2A(PP2A),and tau phosphorylation has been investigated in order to provide experimental basis for mechanism of downregulation of PP2A activity and tau abnormal hyperphosphorylation in Alzheimer's disease brain.Methods: Specific Src SiRNA was transfected into cultured mouse neuroblastoma N2a cells to block the expression of Src protein,then phosphorylation levels of PP2A Y307 and tau at different sites,and PP2A activity were detected at different time points.Results: Twelve hours after the SiRNA transfection,the protein level of Src was decreased dramatically,with decreased PP2A Y307 phosphorylation.But the total PP2A protein level was also decreased,together with a decreased activity of PP2A.Tau was hyperphosphorylated at Ser198/199/202 sites.Conclusion: Multiple factors may be involved in the cellular regulation of PP2A activity.Blocking the Src expression could induce inactivation of PP2A and tau hyperphosphorylation.