The novel tyrosine kinase ZAK1 activates GSK3 to direct cell fate specification

Cell. 1999 Nov 12;99(4):399-408. doi: 10.1016/s0092-8674(00)81526-3.


Inhibition of GSK3 by 7-TM Wnt/wg receptor signaling is critical for specifying embryonic cell fate patterns. In Dictyostelium, the 7-TM cAMP receptors regulate GSK3 by parallel, antagonistic pathways to establish a developmental body plan. We describe here a novel tyrosine kinase, ZAK1, downstream of 7-TM cAMP receptor signaling that is required for GSK3 activation during development. zak1-nulls have reduced GSK3 activity and are defective in GSK3-regulated developmental pathways. Moreover, recombinant ZAK1 phosphorylates and activates GSK3 in vitro. We propose that ZAK1 is a positive regulator of GSK3 activity required for cell pattern formation in Dictyostelium and speculate that similar mechanisms exist to antagonize Wnt/wg signaling for metazoan cell fate specification.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Calcium-Calmodulin-Dependent Protein Kinases / genetics
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Cloning, Molecular
  • Cyclic AMP / metabolism
  • DNA, Complementary
  • Dictyostelium / enzymology*
  • Dictyostelium / growth & development
  • Enzyme Activation
  • Glycogen Synthase Kinase 3
  • Molecular Sequence Data
  • Phosphorylation
  • Protein-Tyrosine Kinases / classification
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism*
  • Rabbits
  • Receptors, Cyclic AMP / metabolism


  • CAR3 protein, Dictyostelium discoideum
  • DNA, Complementary
  • Receptors, Cyclic AMP
  • Cyclic AMP
  • Protein-Tyrosine Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Glycogen Synthase Kinase 3

Associated data

  • GENBANK/AF200688