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The apoptosis-inducing protein kinase DRAK2 is inhibited in a calcium-dependent manner by the calcium-binding protein

Hiroshi Kuwahara1, Jun-ichi Kamei, Norihiro Nakamura

  • 1Department of Biological Science, Graduate School of Science, Osaka University, Machikaneyama, Toyonaka, Osaka 560-0043.

Journal of Biochemistry
|September 11, 2003
PubMed

Insights

Calcineurin homologous protein (CHP) inhibits the apoptosis-inducing protein kinase DRAK2. This calcium-dependent regulation by CHP impacts DRAK2

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Biochemistry

Background:

  • Calcineurin homologous protein (CHP) is an EF-hand Ca(2+)-binding protein.
  • CHP interacts with various cellular proteins, including the apoptosis-inducing protein kinase DRAK2.

Purpose of the Study:

  • To investigate the role of CHP in regulating DRAK2 protein kinase activity in vitro.
  • To determine the Ca(2+)-dependency of CHP's interaction with and inhibition of DRAK2.

Main Methods:

  • In vitro kinase assays were performed to measure DRAK2 activity.
  • Autophosphorylation and exogenous substrate (myosin light chain) phosphorylation by DRAK2 were assessed.
  • The effect of CHP on DRAK2 activity was evaluated under varying Ca(2+) conditions.

Main Results:

  • CHP significantly inhibited DRAK2 kinase activity by approximately 85%.
  • This inhibition was observed for both DRAK2 autophosphorylation and substrate phosphorylation.
  • CHP's inhibitory effect was dependent on the presence of Ca(2+).
  • The physical interaction between CHP and DRAK2 was not Ca(2+)-dependent.

Conclusions:

  • CHP negatively regulates the apoptosis-inducing protein kinase DRAK2.
  • This negative regulation is dependent on intracellular Ca(2+) concentration.
  • CHP acts as a Ca(2+)-sensitive inhibitor of DRAK2 activity.

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