Interaction partners of Dlk/ZIP kinase: Co-expression of Dlk/ZIP kinase and Par-4 results in cytoplasmic retention and apoptosis

Grit Page, Donat Kögel, Vivek Rangnekar, Karl Heinz Scheidtmann

Research output: Contribution to journalArticlepeer-review

99 Scopus citations


Dlk/ZIP kinase is a newly discovered serine/threonine kinase which, due to its homology to DAP kinase, was named DAP like kinase, Dlk. This kinase is tightly associated with nuclear structures, it undergoes extensive autophosphorylation and phosphorylates myosin light chain and core histones H3, H2A and H4 in vitro. Moreover, it possesses a leucine zipper which mediates interaction with transcription factor ATF-4, therefore it was called ZIP kinase. We employed the yeast two-hybrid system to identify interaction partners of Dlk that might serve as regulators or targets. Besides ATF-4 and others we found Par-4, a modulator of transcription factor WT1 and mediator of apoptosis. Complex formation between Dlk and Par-4 was confirmed by GST pull-down experiments and kinase reactions in vitro and coexpression experiments in vivo. The interaction domain within Dlk was mapped to an arginine-rich region between residues 338-417, rather than to the leucine zipper. Strikingly, coexpression of Dlk and Par-4 lead to relocation of Dlk from the nucleus to the cytoplasm, particularly to actin filaments. These interactions provoked a dramatic reorganization of the cytoskeleton and morphological symptoms of apoptosis, thus suggesting a functional relationship between Dlk and Par-4 in the control of apoptosis.

Original languageEnglish
Pages (from-to)7265-7273
Number of pages9
Issue number51
StatePublished - Dec 2 1999

Bibliographical note

Funding Information:
We thank Gerd Landsberg for excellent technical assistance, Ute Preuss for helpful suggestions and critical reading of the manuscript. This work was supported by the Deutsche Forschungsgemeinschaft, Graduierten Kolleg `Functional protein domains' and by means from the Fond der Chemischen Industrie to KH Scheidtmann.


  • Actin filaments
  • Apoptosis
  • Dlk/ZIP kinase
  • Leucine zipper
  • Par-4
  • Two hybrid interaction screen

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research


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