Identification of a New Form of Death-associated Protein Kinase that Promotes Cell Survival

Yijun Jin, Emily K. Blue, Shelley Dixon, Ling Hou, Robert B. Wysolmerski, Patricia J. Gallagher

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

In this study, two alternatively spliced forms of the mouse death-associated protein kinase (DAPK) have been identified and their roles in apoptosis examined. The mouse DAPK-α sequence is 95% identical to the previously described human DAPK, and it has a kinase domain and calmodulin-binding region closely related to the 130-150 kDa myosin light chain kinases. A 12-residue extension of the carboxyl terminus of DAPK-β distinguishes it from the human and mouse DAPK-α. DAPK phosphorylates at least one substrate in vitro and in vivo, the myosin II regulatory light chain. This phosphorylation occurs preferentially at Ser-19 and is stimulated by calcium and calmodulin. The mRNA encoding DAPK is widely distributed and detected in mouse embryos and most adult tissues, although the expression of the encoded 160-kDa DAPK protein is more restricted. Overexpression of DAPK-α, the mouse homolog of human DAPK has a negligible effect on tumor necrosis factor (TNF)-induced apoptosis. Overexpression of DAPK-β has a strong cytoprotective effect on TNF-treated cells. Biochemical analysis of TNF-treated cell lines expressing mouse DAPK-β suggests that the cytoprotective effect of DAPK is mediated through both intrinsic and extrinsic apoptotic signaling pathways and results in the inhibition of cytochrome c release from the mitochondria as well as inhibition of caspase-3 and caspase-9 activity. These results suggest that the mouse DAPK-β is a negative regulator of TNF-induced apoptosis.

Original languageEnglish (US)
Pages (from-to)39667-39678
Number of pages12
JournalJournal of Biological Chemistry
Volume276
Issue number43
DOIs
StatePublished - Oct 26 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Identification of a New Form of Death-associated Protein Kinase that Promotes Cell Survival'. Together they form a unique fingerprint.

  • Cite this

    Jin, Y., Blue, E. K., Dixon, S., Hou, L., Wysolmerski, R. B., & Gallagher, P. J. (2001). Identification of a New Form of Death-associated Protein Kinase that Promotes Cell Survival. Journal of Biological Chemistry, 276(43), 39667-39678. https://doi.org/10.1074/jbc.M101886200