ZIP kinase, a novel serine/threonine kinase which mediates apoptosis

Mol Cell Biol. 1998 Mar;18(3):1642-51. doi: 10.1128/MCB.18.3.1642.


We have identified a novel serine/threonine kinase, designated ZIP kinase, which mediates apoptosis. ZIP kinase contains a leucine zipper structure at its C terminus, in addition to a kinase domain at its N terminus. ZIP kinase physically binds to ATF4, a member of the activating transcription factor/cyclic AMP-responsive element-binding protein (ATF/CREB) family, through interaction between their leucine zippers. The leucine zipper domain is necessary for the homodimerization of ZIP kinase as well as for the activation of kinase. Immunostaining study showed that ZIP kinase localizes in the nuclei. Overexpression of intact ZIP kinase but not catalytically inactive kinase mutants led to the morphological changes of apoptosis in NIH 3T3 cells, suggesting that the cell death-inducing activity of ZIP kinase depends on its intrinsic kinase activity. Interestingly, the catalytic domain of ZIP kinase is closely related to that of death-associated protein kinase (DAP kinase), which is a mediator of apoptosis induced by gamma interferon. Therefore, both ZIP and DAP kinases represent a novel kinase family, which mediates apoptosis through their catalytic activities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Activating Transcription Factor 4
  • Amino Acid Sequence
  • Animals
  • Apoptosis Regulatory Proteins
  • Apoptosis*
  • Base Sequence
  • Binding Sites
  • COS Cells
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Catalysis
  • Cell Nucleus / metabolism
  • Cloning, Molecular
  • DNA, Complementary
  • Death-Associated Protein Kinases
  • Humans
  • Interferon-gamma / pharmacology
  • Leucine Zippers*
  • Mice
  • Molecular Sequence Data
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Sequence Homology, Amino Acid
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • ATF4 protein, human
  • Apoptosis Regulatory Proteins
  • DNA, Complementary
  • Transcription Factors
  • Activating Transcription Factor 4
  • Interferon-gamma
  • Death-Associated Protein Kinases
  • Protein Serine-Threonine Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases

Associated data

  • GENBANK/AB007143
  • GENBANK/AB007144