DAPK2 Antibody
- Known as:
- DAPK2 Antibody
- Catalog number:
- Y107988
- Product Quantity:
- 100 ug
- Category:
- -
- Supplier:
- ABM
- Gene target:
- DAPK2 Antibody
Related genes to: DAPK2 Antibody
- Gene:
- DAPK2 NIH gene
- Name:
- death associated protein kinase 2
- Previous symbol:
- -
- Synonyms:
- DRP-1, MGC119312
- Chromosome:
- 15q22.31
- Locus Type:
- gene with protein product
- Date approved:
- 1999-10-19
- Date modifiied:
- 2016-10-05
Related products to: DAPK2 Antibody
Related articles to: DAPK2 Antibody
- Metastasis and associated therapy resistance remain the principal drivers of cancer related death, and there is a pressing need for a deeper mechanistic understanding and anti-metastatic therapies. For patients that suffer from hepatocellular carcinomas (HCCs), which are the most common primary liver cancers, frequent systemic metastasis results in bleak 5-year survival prognoses of only 4%. To metastasize, carcinoma cells must acquire an invasive phenotype, which typically requires switching from an epithelial-like apical-basal polarity to the front-rear polarity of mesenchymal-like cells. Signaling cues that originate in the tumor microenvironment can activate cellular morphogenic programs that drive polarity switching, like the epithelial-mesenchymal transition (EMT). Protein kinases control most cell signaling pathways and are highly actionable drug targets; however, systematic studies determining the kinases that underly the epithelial-mesenchymal polarity switch (EMPS) are lacking. We developed an assay platform that integrates mass spectrometry (MS)-based kinome profiling, broadly capturing kinase network activity, with chemical genetic screening using selective kinase inhibitors and quantitative phase imaging (QPI), serving as the phenotypic readout. Applying this approach that we dubbed morphokin-MS, to epithelial-like HCC cell lines that we induced to undergo EMPS identified a conserved network of 12 kinases that contributed to HCC cell polarity switching and directed cell migration; MS-based kinome profiling of 17 HCC patient tumors showed that these kinase are frequently upregulated in human tumors. morphokin-MS also revealed that death-associated protein kinase 3 (DAPK3) is one of the principal drivers of the EMPS and directed HCC cell migration. Thus, our mechanistic studies revealed that DAPK3 forms a complex with DAPK1 and filamin-A inter-acting protein 1-like (FILIP1L), which act as scaffold proteins that recruit DAPK3 to the centrosome. Pharmaco-logical and genetic inhibition of the DAPK1-DAPK3-FILIP1L complex blocked centrosome repositioning and microtubule polarization toward the leading edge of mesenchymal-like HCC cells, directed cell migration, and invasion. Our morphokin-MS method and comprehensive kinome profiling data will serve as a valuable resource for the cancer research community; our discovery of an inducible mesenchymal-like DAPK1-DAPK3-FILIP1L polarity complex that controls centrosome positioning in motile HCC cells may lead to the development of novel therapeutics for combatting cancer metastasis. - Source: PubMed
Publication date: 2026/09/18
Rantso Thankhoe AWoods KathrynJensen PaigeWalker Katie AChan Alexandria MMaguire Kathleen MZitnay Rebecca GLovely Lotfa HYang JingshuTakyi AugustineStewart PaulEvason KimberleyJudson-Torres Robert LGolkowski Martin - Although circular RNAs (circRNAs) have been implicated in acute kidney injury (AKI), their functional mechanisms beyond acting as miRNA sponges remain poorly understood, and the role of N6-methyladenosine (m6A) modification in circRNA-mediated regulation in AKI is yet to be explored. Here, we identify a novel mechanism by which the m6A-modified circRNA circNfix contributes to the regulation of septic AKI (SAKI). In tubular epithelial cells (TECs), downregulation of RBM47 reduces circNfix expression during SAKI. m6A-modified circNfix scaffolds the E3 ligase HECTD1 to induce K48-linked polyubiquitination and proteasomal degradation of the m6A reader YTHDF2. This stabilizes DAPK2 mRNA, a key target of YTHDF2, inhibiting NF-κB activation, thereby reducing TEC apoptosis and inflammation. In mouse models of SAKI and ischemia-reperfusion injury-AKI, AAV-mediated circNfix delivery lowered YTHDF2, suppressed inflammation, improved renal function, and attenuated damage. In septic AKI patients, circNfix levels in plasma and urine were significantly decreased, negatively correlated with serum creatinine. Urinary and plasma circNfix showed diagnostic potential. Our study reveals a mechanism where an m6A-modified circRNA contributes to AKI progression by degrading its reader protein, suggesting that circNfix may represent a potential therapeutic target and non-invasive biomarker. - Source: PubMed
Publication date: 2026/09/15
Ma TongtongZhang ZiqiYang YilinChen ChaopengLi ZhiyiLuo HuashengYu YanmeiHuang HeChen ZhongqingWang Peng - Death-associated protein kinase 1 (DAPK1) is a key regulator of apoptosis and immune responses; however, its prognostic significance in oral cancer remains insufficiently characterized. This study investigated the prognostic relevance of DAPK1 in oral squamous cell carcinoma (OSCC) and examined its associations with immune infiltration and apoptosis-related signaling pathways. - Source: PubMed
Publication date: 2026/08/28
Lai Hsiao-ChiChang Keng-MingLee Ching-Chih - Excess neutrophil apoptosis and the release of neutrophil extracellular traps (NETs) in systemic lupus erythematosus (SLE) lead to the accumulation of cell debris and the production of auto-antibodies targeting nuclear proteins and DNA. SLE neutrophil activation is regulated by changes in gene expression, notably expression of type I interferon-response genes and genes coding for granule proteins. This observational study measured both mRNA and small noncoding RNAs in SLE (n = 11) and healthy control (HC, n = 10) ultra-pure blood neutrophils to identify changes in expression that are involved in regulating neutrophil phenotype. Using RNAseq, we identified significant differential expression (DE) of 69 microRNAs, 63 other small noncoding RNAs, 236 piwiRNAs, and 83 tRNA fragments in SLE neutrophils compared to HC (false discovery rate [FDR] adj. P < 0.05). We also identified 78 significant alternative splicing events across 64 genes (FDR adj. P < 0.05, Δpercent spliced in (PSI) > 0.1 or < -0.1). Bioinformatic analysis of miRNA:mRNA DE genes predicted significant activation of autophagy, neutrophil degranulation, interferon alpha/beta signaling, and apoptosis pathways in SLE neutrophils. Translation and mRNA processing were predicted to be downregulated. microRNAs implicated in NETs production were miR-155-5p, miR-146a-5p, and miR-let-7b-5p (FDR adj. P < 0.05). SNORD89 was identified as a potential promoter of apoptosis in SLE neutrophils, along with alternative splicing of apoptosis genes myeloid cell leukemia-1 (MCL1), caspase-8 (CASP8), and death-associated protein kinase-2 (DAPK2) (FDR adj. P < 0.05). Our study, for the first time, describes dysregulated expression of small noncoding RNAs in SLE neutrophils and proposes noncoding RNA and alternative gene splicing as regulators of neutrophil-driven disease pathology in SLE. - Source: PubMed
Filbertine GraceChabronova AlzbetaLiu XuanHaldenby SamThomas Huw BattenMcLaren ZoePeffers Mandy JayneWright Helen Louise - Sepsis is associated with a pronounced but poorly understood endoplasmic reticulum stress (ERS) response. In this study, we found that death-associated protein kinase 2 (DAPK2), a calcium/calmodulin-regulated serine/threonine kinase, exhibits elevated expression in macrophages from patients with sepsis and from septic mice. Macrophage DAPK2 expression is transcriptionally upregulated through the activation of the Toll-like receptor 4 (TLR4)-myeloid differentiation primary response 88 (MyD88)-nuclear factor-κB (NF-κB) pathway. Macrophage-specific deletion of DAPK2 attenuated sepsis severity and mitigated the ERS response. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we identified heat shock protein family A member 5 (HSPA5) as a binding partner for DAPK2. Because DAPK2 function had been previously associated with the kinase activity, we speculated that it might control ERS of macrophages through HSPA5 phosphorylation. Further investigation indeed revealed that DAPK2 phosphorylates HSPA5 at serine-588, which promotes the proteasomal degradation of HSPA5 and subsequently leads to the activation of inositol-requiring enzyme 1α (IRE1α). Inhibition of HSPA5 exacerbated sepsis in mice with macrophage-specific DAPK2 deficiency; however, this effect was abrogated by the deactivation of IRE1α. In conclusion, our findings demonstrate that DAPK2 propagates macrophage ERS through the HSPA5-IRE1α axis during systemic infection, suggesting this pathway as a potential therapeutic target in sepsis. - Source: PubMed
Publication date: 2026/06/23
Ni YinTang Guo-ZhenQiu ChenZhu GeJin Shu-WenZhu Hai-PingMo Shi-JingFang Xiang-Ming