Disease relevance of DAPK3

• A total of 528 men, including 214 treated for clinically localized prostate cancer (41 with evidence of metastatic disease were excluded from this analysis) and 273 age-matched, ZIP code-matched comparison patients without prostate cancer [1].
• PARTICIPANTS--A total of 2.1 million adults residing within the boundaries of the Maryland Regional ESRD Registry, grouped by race and ZIP code into 26 subpopulations [2].
• RESULTS: Compared with whites, blacks were less likely to complete steps B (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.61-0.76), C (OR, 0.56; 95% CI, 0.48-0.65), and D (OR, 0.50; 95% CI, 0.40-0.62) after adjustment for age, sex, cause of renal failure, years receiving dialysis, and median income of patient ZIP code [3].
• Vietnam service and military service experiences of 281 men with sarcomas of soft tissues were compared in this epidemiologic study to a control group of men derived from driver's license files and matched on 5-year period of birth and ZIP code of residence [4].
• Examination of the Blast Bank samples from 22 patients with MDS, 31 with AML, and 8 with chronic myeloid leukemia confirmed the highly selective expression of the Dlk gene in the individuals with MDS [5].

Psychiatry related information on DAPK3

• The authors used ZIP codes to designate rural or urban residence and categorized outpatient utilization into primary care, individual mental health care, non-mental health specialty care, or emergency room care [6].

High impact information on DAPK3

• The bZIP DNA-binding proteins are characterized by a 50-amino-acid DNA binding and dimerization motif, consisting of a highly basic DNA-binding region ('b') followed by a leucine zipper dimerization region ('ZIP') [7].
• Sustained MLC(20) phosphorylation is probably induced by the Ca(2+)-independent MLCK, ZIP kinase [8].
• These results suggest that ZIP kinase is critical for myosin phosphorylation and necessary for cell motile processes in mammalian fibroblasts [9].
• Here, we found that zipper-interacting protein (ZIP) kinase plays a predominant role in myosin II phosphorylation in mammalian fibroblasts [9].
• In T(EM) cells, Kv1.3 traffics to the immunological synapse during antigen presentation where it colocalizes with Kvbeta2, SAP97, ZIP, p56(lck), and CD4 [10].

Chemical compound and disease context of DAPK3

• Under similar conditions, up to 70% of the total immunoreactive FGF2 in transfected endothelial cells (MAE ZIP) or untransfected rat (C6) and human (U87MG) glioblastoma cell lines was detected on their cell surface [11].
• Adjuvant goserelin in pre-menopausal patients with early breast cancer: Results from the ZIPP study [12].
• The Zoladex In Pre-menopausal Patients (ZIPP) study was designed to determine whether addition of goserelin ('Zoladex') and/or tamoxifen to adjuvant therapy (radiotherapy and/or chemotherapy), provided benefit to pre- or peri-menopausal women with operable, early breast cancer [12].
• RESULTS: Among long-term residents, pancreatic cancer mortality was elevated for those living in ZIP codes with the highest use of four pesticides: 1,3-dichloropropene (1,3-d), captafol, pentachloronitrobenzene (PCNB), and dieldrin [13].

Biological context of DAPK3

• ZIP kinase (ZIPK) is a proapoptotic protein kinase with homology to DAP kinase, a protein kinase implicated in apoptosis [14].
• The down-regulated genes include IL8, IL10RA, DAPK3, and those involved in nuclear factor of activated T cells (NFAT) signal pathway and endocrine responsiveness [15].
• High stringency screening of a human aortic cDNA library for the SMPP-1M-associated kinase identified 18 positive clones, all of which proved to be clones of hZIPK [16].
• C-terminal truncation of Dlk/ZIP kinase leads to abrogation of nuclear transport and high apoptotic activity [17].
• Taken together, these data strongly suggest a functional role for Dlk in control of cell survival which is dependent on its subcellular localization [17].

Anatomical context of DAPK3

• Here we show that only native hZIPK mRNA and protein are detectable in human vascular smooth muscle cells (VSMCs) [16].
• ZIP kinase identified as a novel myosin regulatory light chain kinase in HeLa cells [18].
• In this model, ZIP potentiated the inhibitory action of Grb14 on insulin-induced oocyte maturation [19].
• To this end, we have cloned smooth muscle zipper-interacting protein (ZIP) kinase cDNA [20].
• Abrogation of phosphorylation of Thr299, Thr306, and Ser311 had little effect on enzyme activity, but mutation of Thr299 and Thr300 to alanine resulted in redistribution of ZIPK from the cytosol to the nucleus [21].

Associations of DAPK3 with chemical compounds

• Arsenic trioxide (As(2)O(3)) and gamma interferon (IFN-gamma), which accentuate POD formation, increased the association of ZIPK with PODs [14].
• Dlk (also termed ZIP kinase) is a novel serine/threonine kinase with a unique C-terminal domain that is rich in arginine and contains three putative NLS motifs and a functional lecuine zipper [17].
• Here we found that HeLa ZIPK phosphorylated the regulatory light chain of myosin II (MRLC) at both serine 19 and threonine 18 in a Ca2+/calmodulin independent manner [18].
• The interaction domain within Dlk was mapped to an arginine-rich region between residues 338 - 417, rather than to the leucine zipper [22].
• A mutant ZIP kinase construct, in which the six serine/threonine residues were mutated to aspartic acid to mimic the phosphorylated state, was found predominantly in the cytoplasm as a trimer and possessed greater cell death-inducing potency [23].

Enzymatic interactions of DAPK3

• ZIPK also binds and phosphorylates proapoptotic protein Par-4 [14].
• Furthermore, DAP kinase phosphorylates ZIP kinase at six specific sites within its extracatalytic C-terminal domain [23].

Regulatory relationships of DAPK3

• TCP10L is expressed specifically in spermatogenic cells and binds to death associated protein kinase-3 [24].
• Significantly, modification of the DAP kinase phosphorylation sites influences both the localization and oligomerization status of ZIP kinase [23].

Other interactions of DAPK3

• We show here that ZIPK is present in PODs, where it colocalizes with and binds to proapoptotic protein Daxx [14].
• Association of ZIPK with Daxx was enhanced by coexpression of Par-4 [14].
• Therefore, both ZIP and DAP kinases represent a novel kinase family, which mediates apoptosis through their catalytic activities [25].
• HeLa ZIPK is the first non-muscle MLCK that phosphorylates MRLC at two sites [18].
• Expression of various deletion and point mutations of Dlk as GFP fusion proteins revealed that the leucine zipper is required for association with speckles and the most C-terminal NLS is necessary and sufficient for nuclear transport [17].

Analytical, diagnostic and therapeutic context of DAPK3

• Immunoblotting showed native full-length 52-kDa hZIPK expression in VSMCs [16].
• Northern blotting studies of multiple vascular and non-vascular tissue RNAs, including human bladder RNA, showed only 2.3 kb of mRNA predicted for full-length hZIPK [16].
• To identify the speckle like structures to which Dlk binds we performed immunofluorescence analyses with antibodies directed against representative marker proteins of replication, transcription, or splicing centers [17].
• Assignment of the ZIP kinase gene to human chromosome 19p13.3 by somatic hybrid analysis and fluorescence in-situ hybridization [26].
• MEASUREMENTS: Using univariate and multivariate analyses, bronchodilator and inhaled steroid prescription rates were determined for 45 ZIP codes and studied for associations with race and ethnicity, poverty, educational attainment, marital status, gender, total numbers of asthma drug prescriptions, and numbers and types of asthma care providers [27].

References