Modulation of the glycogen synthase kinase-3 family by tyrosine phosphorylation

EMBO J. 1993 Feb;12(2):803-8.

Abstract

Glycogen synthase kinase-3 (GSK-3) is a protein serine kinase implicated in the cellular response to insulin. The enzyme is the mammalian homologue of the zeste-white3 (shaggy) homeotic gene of Drosophila melanogaster and has been implicated in the regulation of the c-Jun/AP-1 transcription factor. In mammals this protein serine kinase is encoded by two related genes termed GSK-3 alpha and beta. Here, we demonstrate that these two proteins and the fruit fly protein are phosphorylated on tyrosine in vivo. Moreover, GSK-3 beta activity and function are shown to be dependent on tyrosine phosphorylation. The modified tyrosine residue is conserved in all members of the GSK-3 family and is equivalent to that required for activity by mitogen-activated protein (MAP) kinases. However, unlike MAP kinases, GSK-3 is highly phosphorylated on tyrosine and thus active in resting cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Cattle
  • Cells, Cultured
  • Cloning, Molecular
  • DNA
  • Glycogen Synthase Kinases
  • Humans
  • Molecular Sequence Data
  • Moths
  • Phosphorylation
  • Protein Kinases / chemistry
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • Rabbits
  • Rats
  • Sequence Homology, Amino Acid
  • Tyrosine / metabolism*

Substances

  • Tyrosine
  • DNA
  • Protein Kinases
  • Glycogen Synthase Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases