The death-associated protein kinases: structure, function, and beyond

Annu Rev Biochem. 2006:75:189-210. doi: 10.1146/annurev.biochem.75.103004.142615.


Death-associated protein kinase (DAPk) is the founding member of a newly classified family of Ser/Thr kinases, whose members not only possess significant homology in their catalytic domains, but also share cell death-associated functions. The realization that DAPk is a tumor suppressor gene, whose expression is lost in multiple tumor types, has spurred a flurry of interest in the kinase family and produced an impressive body of literature concerning its function, regulation, and connection to disease. The DAPk family has been linked to several cell death-related signaling pathways, and functions other than cell death have also been proposed. This review presents a thorough structural analysis of the kinases, discusses methods of regulation, clarifies their cellular targets and functions, and shows how these functions are integrated. Although many gaps in our knowledge still remain, the data generated to date can be combined to delineate a place for the DAPk family within the general cell death-signaling network.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis Regulatory Proteins* / chemistry
  • Apoptosis Regulatory Proteins* / genetics
  • Apoptosis Regulatory Proteins* / metabolism
  • Autophagy
  • Calcium-Calmodulin-Dependent Protein Kinases* / chemistry
  • Calcium-Calmodulin-Dependent Protein Kinases* / genetics
  • Calcium-Calmodulin-Dependent Protein Kinases* / metabolism
  • Cell Death*
  • Cytoskeleton / metabolism
  • Death-Associated Protein Kinases
  • Humans
  • Molecular Sequence Data
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Serine-Threonine Kinases / chemistry
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Sequence Alignment
  • Signal Transduction / physiology*


  • Apoptosis Regulatory Proteins
  • Protein Isoforms
  • Death-Associated Protein Kinases
  • Protein Serine-Threonine Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases