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Review
. 2015 Jul;47(1):5-15.
doi: 10.3892/ijo.2015.2998. Epub 2015 May 11.

Death-associated protein kinase: A molecule with functional antagonistic duality and a potential role in inflammatory bowel disease (Review)

Sara Steinmann  1 , Kristina Scheibe  2 , Katharina Erlenbach-Wuensch  3 , Clemens Neufert  2 , Regine Schneider-Stock  1
Affiliations
Review

Death-associated protein kinase: A molecule with functional antagonistic duality and a potential role in inflammatory bowel disease (Review)

Sara Steinmann et al. Int J Oncol. 2015 Jul.

Abstract

The cytoskeleton-associated serine/threonine kinase death-associated protein kinase (DAPK) has been described as a cancer gene chameleon with functional antagonistic duality in a cell type and context specific manner. The broad range of interaction partners and substrates link DAPK to inflammatory processes especially in the gut. Herein we summarize our knowledge on the role of DAPK in different cell types that play a role under inflammatory conditions in the gut. Besides some promising experimental data suggesting DAPK as an interesting drug target in inflammatory bowel disease there are many open questions regarding direct evidence for a role of DAPK in intestinal inflammation.

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Figures

Figure 1
Figure 1
Structure of different isoforms and functional domains of DAPK family members. Percentage gives structural similarity to the DAPK molecule.
Figure 2
Figure 2
DAPK can be expressed by various cell types including intestinal epithelial cells (IECs) as well as innate and adaptive immune cells typically populating the gut in inflammatory bowel disease (IBD) and colitis-associated cancer (CAC). Further studies are needed to reveal context dependent contributions of DAPK in intestinal cell types potentially modulating the course of intestinal inflammation and/or CAC. Innate lymphoid cell (ILC), polymorphonuclear cells (PMN).
Figure 3
Figure 3
DAPK expression in inflammation (x10 and ×40 fold magnification) (A1 and A2) Example of regular mucosa of the colon with mild inflammation (H&E, →). (A3 and A4) Diffuse expression of DAPK in the cytoplasm of lymphocytes, plasma cells and macrophages in the interstitium. (→) and loss of expression in epithelial cells of colon mucosa (➤). (B1 and B2) Example of severe colitis with crypt architectural distorsion and chronic as well as acute inflammatory cells (H&E, →). (B3 and B4) Strong expression of DAPK in the cytoplasm of inflammatory cells (→). Mild expression in epithelial cells of colon mucosa (➤). (C1 and C2) Example of colorectal carcinoma with intratumoral inflammatory reaction. (C3 and C4) Strong expression of DAPK in the cytoplasm of both, inflammatory cells (→) and tumor cells (➤).
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