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Death-associated protein kinase 2 is a new calcium/calmodulin-dependent protein kinase that signals apoptosis through its catalytic activity

Oncogene volume 18, pages 3471–3480 (1999)Cite this article

Abstract

We have identified and characterized a new calcium/calmodulin (Ca2+/CaM) dependent protein kinase termed death-associated protein kinase 2 (DAPK2) that contains an N-terminal protein kinase domain followed by a conserved CaM-binding domain with significant homologies to those of DAP kinase, a protein kinase involved in apoptosis. DAPK2 mRNA is expressed abundantly in heart, lung and skeletal muscle. The mapping results indicated that DAPK2 is located in the central region of mouse chromosome 9. In vitro kinase assay revealed that DAPK2 is autophosphorylated and phosphorylates myosin light chain (MLC) as an exogenous substrate. DAPK2 binds directly to CaM and is activated in a Ca2+/CaM-dependent manner. A constitutively active DAPK2 mutant is generated by removal of the CaM-binding domain (ΔCaM). Treatment of agonists that elevate intracellular Ca2+-concentration led to the activation of DAPK2 and transfection studies revealed that DAPK2 is localized in the cytoplasm. Overexpression of DAPK2, but not the kinase negative mutant, significantly induced the morphological changes characteristic of apoptosis. These results indicate that DAPK2 is an additional member of DAP kinase family involved in apoptotic signaling.

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Acknowledgements

We thank T Aoki and M Hyuga for excellent secretarial assistance, and Deborah B Householder for excellent technical assistance. This work was supported by grants from the Ministry of Education of Japan and in part by the National Cancer Institute, DHHS, under contract with ABL.

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Authors and Affiliations

  1. Department of Biochemistry, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, 663-8501, Hyogo, Japan

    Taro Kawai, Fumiko Nomura, Katsuaki Hoshino & Shizuo Akira

  2. Mammalian Genetics Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, MD 21702, Maryland, USA

    Neal G Copeland, Debra J Gilbert & Nancy A Jenkins

  3. CREST of Japan Science and Technology Corporation, Japan

    Taro Kawai, Fumiko Nomura, Katsuaki Hoshino & Shizuo Akira

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  1. Taro Kawai
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Kawai, T., Nomura, F., Hoshino, K. et al. Death-associated protein kinase 2 is a new calcium/calmodulin-dependent protein kinase that signals apoptosis through its catalytic activity. Oncogene 18, 3471–3480 (1999). https://doi.org/10.1038/sj.onc.1202701

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