Overexpression of the mouse dishevelled-1 protein inhibits GSK-3beta-mediated phosphorylation of tau in transfected mammalian cells

FEBS Lett. 1997 Jul 14;411(2-3):369-72. doi: 10.1016/s0014-5793(97)00733-3.

Abstract

Tau is a neuronal microtubule-associated protein whose function is modulated by phosphorylation. GSK-3beta is a tau kinase. GSK-3beta is part of the wingless signalling pathway and stimulation by wingless is predicted to down-regulate GSK-3beta activity. In Drosophila imaginal disc cells, overexpression of dishevelled, a component of the wingless pathway, mimics the wingless signal. We have therefore studied the effect that overexpression of the murine dishevelled-1 protein has on GSK-3beta-mediated phosphorylation of tau in transfected CHO cells. We find that co-transfection with dishevelled-1 is inhibitory to GSK-3beta-mediated tau phosphorylation. Tau is hyperphosphorylated in Alzheimer's disease and the possible relevance of these findings to Alzheimer's disease pathogenesis are discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Blotting, Western
  • CHO Cells
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Cloning, Molecular
  • Cricetinae
  • Dishevelled Proteins
  • Drosophila / genetics
  • Drosophila Proteins
  • Gene Expression Regulation
  • Glycogen Synthase Kinase 3
  • Humans
  • Insect Proteins / metabolism*
  • Mice
  • Phosphoproteins / genetics*
  • Phosphorylation
  • Signal Transduction
  • Transfection
  • tau Proteins / genetics
  • tau Proteins / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • DVL1 protein, human
  • Dishevelled Proteins
  • Drosophila Proteins
  • Dvl1 protein, mouse
  • Insect Proteins
  • Phosphoproteins
  • dsh protein, Drosophila
  • tau Proteins
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Glycogen Synthase Kinase 3