Death-associated protein kinase 3

Definition:

Serine/threonine kinase which is involved in the regulation of apoptosis, autophagy, transcription, translation and actin cytoskeleton reorganization. Involved in the regulation of smooth muscle contraction. Regulates both type I (caspase-dependent) apoptotic and type II (caspase-independent) autophagic cell deaths signal, depending on the cellular setting. Involved in regulation of starvation-induced autophagy. Regulates myosin phosphorylation in both smooth muscle and non-muscle cells. In smooth muscle, regulates myosin either directly by phosphorylating MYL12B and MYL9 or through inhibition of smooth muscle myosin phosphatase (SMPP1M) via phosphorylation of PPP1R12A; the inhibition of SMPP1M functions to enhance muscle responsiveness to Ca(2+) and promote a contractile state. Phosphorylates MYL12B in non-muscle cells leading to reorganization of actin cytoskeleton. Isoform 2 can phosphorylate myosin, PPP1R12A and MYL12B. Overexpression leads to condensation of actin stress fibers into thick bundles. Involved in actin filament focal adhesion dynamics. The function in both reorganization of actin cytoskeleton and focal adhesion dissolution is modulated by RhoD. Positively regulates canonical Wnt/beta-catenin signaling through interaction with NLK and TCF7L2. Phosphorylates RPL13A on 'Ser-77' upon interferon-gamma activation which is causing RPL13A release from the ribosome, RPL13A association with the GAIT complex and its subsequent involvement in transcript-selective translation inhibition. Enhances transcription from AR-responsive promoters in a hormone- and kinase-dependent manner. Involved in regulation of cell cycle progression and cell proliferation. May be a tumor suppressor.

References:

[1]. Norio Takamoto, et al. Novel ZIP kinase isoform lacks leucine zipper. Arch Biochem Biophys. 2006 Dec 15;456(2):194-203. [Content Brief]

[2]. Noriko Sato, et al. Physical and functional interactions between STAT3 and ZIP kinase. Int Immunol. 2005 Dec;17(12):1543-52. [Content Brief]

[3]. Taro Kawai, et al. ZIP kinase triggers apoptosis from nuclear PML oncogenic domains. Mol Cell Biol. 2003 Sep;23(17):6174-86. [Content Brief]

[4]. P Leister, et al. ZIP kinase plays a crucial role in androgen receptor-mediated transcription. Oncogene. 2008 May 22;27(23):3292-300. [Content Brief]

[5]. Laura Hagerty, et al. ROCK1 phosphorylates and activates zipper-interacting protein kinase. J Biol Chem. 2007 Feb 16;282(7):4884-4893. [Content Brief]

[6]. M Murata-Hori, et al. ZIP kinase identified as a novel myosin regulatory light chain kinase in HeLa cells. FEBS Lett. 1999 May 14;451(1):81-4. [Content Brief]

[7]. John Brognard, et al. Cancer-associated loss-of-function mutations implicate DAPK3 as a tumor-suppressing kinase. Cancer Res. 2011 Apr 15;71(8):3152-61. [Content Brief]

[8]. Yishay Shoval, et al. New modularity of DAP-kinases: alternative splicing of the DRP-1 gene produces a ZIPk-like isoform. PLoS One. 2011 Mar 8;6(2):e17344. [Content Brief]

[9]. Hong-Wen Tang, et al. Atg1-mediated myosin II activation regulates autophagosome formation during starvation-induced autophagy. EMBO J. 2011 Feb 16;30(4):636-51. [Content Brief]

[10]. Rupak Mukhopadhyay, et al. DAPK-ZIPK-L13a axis constitutes a negative-feedback module regulating inflammatory gene expression. Mol Cell. 2008 Nov 7;32(3):371-82. [Content Brief]

[11]. Vishal Nehru, et al. Interaction of RhoD and ZIP kinase modulates actin filament assembly and focal adhesion dynamics. Biochem Biophys Res Commun. 2013 Apr 5;433(2):163-9. [Content Brief]

[12]. N Niiro, et al. Zipper-interacting protein kinase induces Ca(2+)-free smooth muscle contraction via myosin light chain phosphorylation. J Biol Chem. 2001 Aug 3;276(31):29567-74. [Content Brief]

[13]. Satoshi Komatsu, et al. ZIP kinase is responsible for the phosphorylation of myosin II and necessary for cell motility in mammalian fibroblasts. J Cell Biol. 2004 Apr 26;165(2):243-54. [Content Brief]

[14]. Gidi Shani, et al. Death-associated protein kinase phosphorylates ZIP kinase, forming a unique kinase hierarchy to activate its cell death functions. Mol Cell Biol. 2004 Oct;24(19):8611-26. [Content Brief]

[15]. M Murata-Hori, et al. HeLa ZIP kinase induces diphosphorylation of myosin II regulatory light chain and reorganization of actin filaments in nonmuscle cells. Oncogene. 2001 Dec 13;20(57):8175-83. [Content Brief]

[16]. Sumihito Togi, et al. Zipper-interacting protein kinase (ZIPK) modulates canonical Wnt/beta-catenin signaling through interaction with Nemo-like kinase and T-cell factor 4 (NLK/TCF4). J Biol Chem. 2011 May 27;286(21):19170-7. [Content Brief]

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