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J. Biochem, 2003, Vol. 134, No. 2 245-250
© 2003 Japanese Biochemical Society

CELL

The Apoptosis-Inducing Protein Kinase DRAK2 Is Inhibited in a Calcium-Dependent Manner by the Calcium-Binding Protein CHP

Hiroshi Kuwahara*, Jun-ichi Kamei*, Norihiro Nakamura§, Miho Matsumoto, Hiroki Inoue and Hiroshi Kanazawa

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

Calcineurin homologous protein (CHP) is an EF-hand Ca2+-binding protein capable of interacting with various cellular proteins including Na+/H+ exchangers, kinesin-related proteins, and apoptosis-inducing protein kinase DRAK2. We investigated the role of CHP on the DRAK2 protein kinase in vitro. CHP significantly reduced (~85% inhibition) the kinase activity of DRAK2 for both autophosphorylation and phosphorylation of exogenous substrate (myosin light chain). The inhibitory effect of CHP was dependent on the presence of Ca2+, whereas the interaction between CHP and DRAK2 was not Ca2+-dependent. These observations suggest that CHP negatively regulates the apoptosis-inducing protein kinase DRAK2 in a manner that depends on intracellular Ca2+-concentration.

* Both authors contributed equally to this work.

§ To whom correspondence should be addressed. Tel: +81-6-6850-5820, Fax: +81-6-6850-5817, E-mail: nnakamur{at}bio.sci.osaka-u.ac.jp


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