Insulin transiently increases tau phosphorylation: Involvement of glycogen synthase kinase-3β and Fyn tyrosine kinase

Mathieu Lesort, Richard S. Jope, Gail V.W. Johnson

Research output: Contribution to journalArticle

198 Scopus citations

Abstract

The modulation of tau phosphorylation in response to insulin was examined in human neuroblastoma SH-SY5Y cells. Insulin treatment resulted in a transient increase in tau phosphorylation followed by a decrease in tau phosphorylation that correlated directly with a sequential activation and deactivation of glycogen synthase kinase-3β (GSK-β). The insulin-induced increase in tau phosphorylation and concurrent activation of GSK-3β was rapid (<2 min) and transient, and was associated with increased tyrosine phosphorylation of GSK-3β. The increase in GSK-3β tyrosine phosphorylation corresponded directly to an increase in the association of Fyn tyrosine kinase with GSK-3β, and Fyn immunoprecipitated from cells treated with insulin for 1 min phosphorylated GSK-3β to a significantly greater extent than Fyn immunoprecipitated from control cells. Subsequent to the increase in GSK-3β activation and tau phosphorylation, treatment of cells with insulin for 60 min resulted in a dephosphorylation of tau and a decrease in GSK-3β activity. Thus, insulin rapidly and transiently activated GSK-3β and modulated tau phosphorylation, alterations that may contribute to neuronal plasticity.

Original languageEnglish (US)
Pages (from-to)576-584
Number of pages9
JournalJournal of neurochemistry
Volume72
Issue number2
DOIs
StatePublished - 1999

Keywords

  • Fyn
  • Glycogen synthase kinase-3β
  • Insulin
  • Phosphorylation
  • Tau

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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