Gene Symbol: WNK2
Description: WNK lysine deficient protein kinase 2
Alias: NY-CO-43, P/OKcl.13, PRKWNK2, SDCCAG43, serine/threonine-protein kinase WNK2, antigen NY-CO-43, mitogen-activated protein kinase kinase kinase, protein kinase lysine-deficient 2, protein kinase with no lysine 2, serologically defined colon cancer antigen 43
Species: human
Products:     WNK2

Top Publications

  1. Verissimo F, Jordan P. WNK kinases, a novel protein kinase subfamily in multi-cellular organisms. Oncogene. 2001;20:5562-9 pubmed
    ..Three additional, partial human protein kinase sequences, WNK2, WNK3 and WNK4, are also reported here with catalytic domains that are 95% homologous to WNK1...
  2. Hong C, Moorefield K, Jun P, Aldape K, Kharbanda S, Phillips H, et al. Epigenome scans and cancer genome sequencing converge on WNK2, a kinase-independent suppressor of cell growth. Proc Natl Acad Sci U S A. 2007;104:10974-9 pubmed
    ..of 31 human infiltrative gliomas and identified low-frequency deletion and highly recurrent epigenetic silencing of WNK2, encoding a putative serine/threonine kinase...
  3. Moniz S, Martinho O, Pinto F, Sousa B, Loureiro C, Oliveira M, et al. Loss of WNK2 expression by promoter gene methylation occurs in adult gliomas and triggers Rac1-mediated tumour cell invasiveness. Hum Mol Genet. 2013;22:84-95 pubmed publisher
    The gene encoding protein kinase WNK2 was recently identified to be silenced by promoter hypermethylation in gliomas and meningiomas, suggesting a tumour-suppressor role in these brain tumours...
  4. Moniz S, Matos P, Jordan P. WNK2 modulates MEK1 activity through the Rho GTPase pathway. Cell Signal. 2008;20:1762-8 pubmed publisher
    ..Human WNK2 has been recently identified as a cell growth regulator that modulates activation of the ERK1/2 protein kinase and ..
  5. Jun P, Hong C, Lal A, Wong J, McDermott M, Bollen A, et al. Epigenetic silencing of the kinase tumor suppressor WNK2 is tumor-type and tumor-grade specific. Neuro Oncol. 2009;11:414-22 pubmed publisher
    ..The predilection for epigenetic rather than genetic silencing was exemplified at the 5' CpG island of WNK2, a serine-threonine kinase gene on chromosome 9q22.31...
  6. Dutruel C, Bergmann F, Rooman I, Zucknick M, Weichenhan D, Geiselhart L, et al. Early epigenetic downregulation of WNK2 kinase during pancreatic ductal adenocarcinoma development. Oncogene. 2014;33:3401-10 pubmed publisher
    ..DNAs from PDACs, chronic pancreatitis (CP) and normal tissues using CpG island microarrays and identified WNK2 as a prominent candidate tumor suppressor gene being downregulated early in PDAC development...
  7. Wilson F, Disse Nicodeme S, Choate K, Ishikawa K, Nelson Williams C, Desitter I, et al. Human hypertension caused by mutations in WNK kinases. Science. 2001;293:1107-12 pubmed
    ..WNK1 is cytoplasmic, whereas WNK4 localizes to tight junctions. The WNK kinases and their associated signaling pathway(s) may offer new targets for the development of antihypertensive drugs...
  8. Moniz S, Verissimo F, Matos P, Brazão R, Silva E, Kotelevets L, et al. Protein kinase WNK2 inhibits cell proliferation by negatively modulating the activation of MEK1/ERK1/2. Oncogene. 2007;26:6071-81 pubmed
    ..Here, we describe the cloning and functional analysis of the human family member WNK2. We show that the depletion of endogenous WNK2 expression by RNA interference in human cervical HeLa cancer cells ..
  9. Sugiyama H, Takahashi K, Yamamoto T, Iwasaki M, Narita M, Nakamura M, et al. Nat1 promotes translation of specific proteins that induce differentiation of mouse embryonic stem cells. Proc Natl Acad Sci U S A. 2017;114:340-345 pubmed publisher
    ..These data collectively show that Nat1 is involved in the translation of proteins that are required for cell differentiation. ..

More Information

Publications128 found, 100 shown here

  1. Kimura A, Namekata K, Guo X, Harada C, Harada T. Dock3-NMDA receptor interaction as a target for glaucoma therapy. Histol Histopathol. 2017;32:215-221 pubmed publisher
    ..We also discuss apoptosis signal-regulating kinase 1 (ASK1), a member of mitogen-activated protein kinase kinase kinase that is a key regulator of cellular responses to oxidative stress, as an innovative therapeutic target for glaucoma. ..
  2. Hoogendijk A, Diks S, Peppelenbosch M, van der Poll T, Wieland C. Kinase activity profiling of gram-negative pneumonia. Mol Med. 2011;17:741-7 pubmed publisher
    ..This study reaffirms the importance of classic inflammation pathways, such as MAPK and TGF? signaling and reveals less known involvement of glycogen synthase kinase 3? (GSK-3?), AKT and SRC signaling cassettes in pneumonia. ..
  3. Kanduc D, Shoenfeld Y. From HBV to HPV: Designing vaccines for extensive and intensive vaccination campaigns worldwide. Autoimmun Rev. 2016;15:1054-1061 pubmed publisher
  4. Petzold H, Rigoulot S, Zhao C, Chanda B, Sheng X, Zhao M, et al. Identification of new protein-protein and protein-DNA interactions linked with wood formation in Populus trichocarpa. Tree Physiol. 2017;:1-16 pubmed publisher
  5. Kim M, Yang H, Kim Y, Kang I, Kim S, Cho Y. Role of nitric oxide and WNK-SPAK/OSR1-KCC2 signaling in daily changes in GABAergic inhibition in the rat dorsal raphe neurons. Neuropharmacology. 2018;135:355-367 pubmed publisher
    ..ex vivo treatment of DRN slices with a NO donor sodium nitroprusside (SNP) increased the expression of KCC2, WNK1, WNK2, WNK3, SPAK, and OSR1, whilst decreasing phosphorylated SPAK...
  6. Li S, Pinard M, Wang Y, Yang L, Lin R, Hiscott J, et al. Crosstalk between the TNF and IGF pathways enhances NF-κB activation and signaling in cancer cells. Growth Horm IGF Res. 2015;25:253-61 pubmed publisher
  7. BELL J, Strobel H. Regulation of cytochrome P450 4F11 by nuclear transcription factor-κB. Drug Metab Dispos. 2012;40:205-11 pubmed publisher
    ..CYP4F11 promoter inhibition can also be rescued in the presence of TNF-α when p65, a NF-κB protein, is knocked down. Thus, NF-κB signaling pathways negatively regulate the CYP4F11 gene. ..
  8. Koeck I, Hashemi Gheinani A, Baumgartner U, Vassella E, Bruggmann R, Burkhard F, et al. Tumor Necrosis Factor-? Initiates miRNA-mRNA Signaling Cascades in Obstruction-Induced Bladder Dysfunction. Am J Pathol. 2018;188:1847-1864 pubmed publisher
    ..The compensatory up-regulation of miR-199a-5p together with TNF-? inhibition may be therapeutically beneficial. ..
  9. Truong A, Hong Y, Lee J, Lee K, Kil D, Lillehoj H, et al. Interleukin-34 Regulates Th1 and Th17 Cytokine Production by Activating Multiple Signaling Pathways through CSF-1R in Chicken Cell Lines. Int J Mol Sci. 2018;19: pubmed publisher
  10. Tang B. (WNK)ing at death: With-no-lysine (Wnk) kinases in neuropathies and neuronal survival. Brain Res Bull. 2016;125:92-8 pubmed publisher
    ..b>WNK2, which is exclusively enriched in neurons, is well known as an anti-proliferative tumor suppressor...
  11. Yen J, Huang S, Huang H, Fong Y, Wu Y, Chiang J, et al. HGK-sestrin 2 signaling-mediated autophagy contributes to antitumor efficacy of Tanshinone IIA in human osteosarcoma cells. Cell Death Dis. 2018;9:1003 pubmed publisher
    ..Our results offer novel mechanistic insight into how TIIA inhibits osteosarcoma growth and suggest TIIA as a promising therapeutic agent for the treatment of cancer. ..
  12. Jiang Y, Li Q, Zhang Y, Gao Y, Jiang L, Chen Z. TIPE2 governs macrophage polarization via negative regulation of mTORC1. Mol Med Rep. 2018;17:952-960 pubmed publisher
    ..Overall, these results define a key role for TIPE2 in macrophage polarization by impeding mTORC1 response. ..
  13. Hu N, Kadota M, Liu H, Abnet C, Su H, Wu H, et al. Genomic Landscape of Somatic Alterations in Esophageal Squamous Cell Carcinoma and Gastric Cancer. Cancer Res. 2016;76:1714-23 pubmed publisher
    ..FGF2, FBXW7, MSH3, PTCH, NF1, ERBB2, and CHEK2, and potentially novel cancer-associated genes, KISS1R, AMH, MNX1, WNK2, and PRKRIR Finally, we identified recurrent chromosome alterations in at least 30% of tumors in genes, including ..
  14. Mir S, Renuse S, Sathe G, Khan A, Patil A, Nanjappa V, et al. Altered signaling associated with chronic arsenic exposure in human skin keratinocytes. Proteomics Clin Appl. 2017;11: pubmed publisher
    ..Our study provides novel insights into signaling perturbations associated with chronic arsenic exposure in human skin keratinocytes. All MS/MS data have been deposited to the ProteomeXchange with identifier PXD004868...
  15. Touat Todeschini L, Shichino Y, Dangin M, Thierry Mieg N, Gilquin B, Hiriart E, et al. Selective termination of lncRNA transcription promotes heterochromatin silencing and cell differentiation. EMBO J. 2017;36:2626-2641 pubmed publisher
    ..These findings reveal an important role for selective termination of lncRNA transcription in both euchromatic and heterochromatic lncRNA-based gene silencing processes. ..
  16. Higashi M, Yoneda M, Nakagawa T, Ikeda M, Ito T. miR-222 regulates proliferation of primary mouse hepatocytes in vitro. Biochem Biophys Res Commun. 2019;: pubmed publisher
    ..Our results suggest that miR-222 is one of the key factors regulating PMH proliferation in vitro. ..
  17. Yu W, Qian C, Jiang X, Zhang F, Weng W. Mechanisms of stem cell osteogenic differentiation on TiO2 nanotubes. Colloids Surf B Biointerfaces. 2015;136:779-85 pubmed publisher
    ..Our results revealed some molecular mechanisms by which TiO2 nanotubes may direct osteogenic differentiation of stem cells. ..
  18. Creytens D, van Gorp J, Speel E, Ferdinande L. Characterization of the 12q amplicons in lipomatous soft tissue tumors by multiplex ligation-dependent probe amplification-based copy number analysis. Anticancer Res. 2015;35:1835-42 pubmed
    ..in DDLPS in 12q13, 12q21 and 12q24, including glioma-associated oncogene homolog 1 (GLI1), mitogen activated protein kinase kinase kinase 12 (MAP3K12), cyclin-dependent kinase 2 (CDK2), ALX homeobox 1 (ALX1) and T-box 5 (TBX5)...
  19. Wu J, Li W, Huang M, Wei H, Wang T, Fan J, et al. Regulation of cancerous progression and epithelial-mesenchymal transition by miR-34c-3p via modulation of MAP3K2 signaling in triple-negative breast cancer cells. Biochem Biophys Res Commun. 2017;483:10-16 pubmed publisher
    ..Future endeavor in this field may help to identify a novel biomarker to predict prognosis and response to therapy in TNBC. ..
  20. Chen Y, Sumardika I, Tomonobu N, Winarsa Ruma I, Kinoshita R, Kondo E, et al. Melanoma cell adhesion molecule is the driving force behind the dissemination of melanoma upon S100A8/A9 binding in the original skin lesion. Cancer Lett. 2019;452:178-190 pubmed publisher
  21. Saleiro D, Blyth G, Kościuczuk E, Ozark P, Majchrzak Kita B, Arslan A, et al. IFN-γ-inducible antiviral responses require ULK1-mediated activation of MLK3 and ERK5. Sci Signal. 2018;11: pubmed publisher
    ..These findings define a previously unknown IFN-γ pathway that appears to be a key element of the antiviral response. ..
  22. Selwa E, Martiny V, Iorga B. Molecular docking performance evaluated on the D3R Grand Challenge 2015 drug-like ligand datasets. J Comput Aided Mol Des. 2016;30:829-839 pubmed
    ..We could evidence that different docking software and scoring functions can behave differently on individual ligand datasets, and that the flexibility of specific binding site residues is a crucial element to provide good predictions. ..
  23. Fujisawa T. Therapeutic application of apoptosis signal-regulating kinase 1 inhibitors. Adv Biol Regul. 2017;66:85-90 pubmed publisher
    ..In this review, we highlight the current understanding of ASK1 inhibitors as a potential therapy for human diseases. ..
  24. Xu D, Matsumoto M, McKenzie B, Zarrin A. TPL2 kinase action and control of inflammation. Pharmacol Res. 2018;129:188-193 pubmed publisher
    ..In parallel to this, TPL2 also activates p38α and p38δ to drive the production of various inflammatory mediators in neutrophils. We discuss the implications of this finding in the context of various inflammatory diseases. ..
  25. Peng H, Liang Y, Tan T, Chuang H, Lin Y, Lin J. RBM4a-SRSF3-MAP4K4 Splicing Cascade Constitutes a Molecular Mechanism for Regulating Brown Adipogenesis. Int J Mol Sci. 2018;19: pubmed publisher
    ..Collectively, the RBM4-SRSF3-MAP4K4 splicing cascade constitutes a novel molecular mechanism in manipulating the development of BAs through related signaling pathways. ..
  26. Liu C, Teng G, Chen M, Ma K, Yan T. [The preliminary study of gene copy number variation association with scar hyperplasia based on the whole-gene resequencing]. Zhonghua Wai Ke Za Zhi. 2014;52:446-9 pubmed
    ..There are 5 CNVs associated with scar hyperplasia. Especially MAP3K15 and MAP4K4 deserve more research to find their function in keloid formation. ..
  27. Huang T, She K, Peng G, Wang W, Huang J, Li J, et al. MicroRNA-186 suppresses cell proliferation and metastasis through targeting MAP3K2 in non-small cell lung cancer. Int J Oncol. 2016;49:1437-44 pubmed publisher
    ..Therefore, miR-186-MAP3K2 may represent a new and useful potential clinical treatment and diagnosis target for NSCLC. ..
  28. Roth Flach R, Danai L, DiStefano M, Kelly M, Menendez L, Jurczyk A, et al. Protein Kinase Mitogen-activated Protein Kinase Kinase Kinase Kinase 4 (MAP4K4) Promotes Obesity-induced Hyperinsulinemia. J Biol Chem. 2016;291:16221-30 pubmed publisher
    ..These results demonstrate that protein kinase Map4k4 drives obesity-induced hyperinsulinemia and insulin resistance in part by promoting insulin secretion from β cells in mice. ..
  29. Zhang J, Tan X, Yuan Z, Li Y, Qi Y, Nan X, et al. [Let-7 miRNA silencing promotes Kaposi's sarcoma-associated herpesvirus lytic replication via activating mitogen-activated protein kinase kinase kinase kinase 4 and its downstream factors]. Zhonghua Zhong Liu Za Zhi. 2016;38:485-91 pubmed publisher
    ..Let-7 silencing may activate the replication of KSHV, possibly through up-regulating MAP4K4 and its downstream molecules COX-2, MMP-13, and phosphorylation of ERK1/2, finally results in the progression of Kaposi sarcoma. ..
  30. Guo S, Liang Y, Murphy S, Huang A, Shen H, Kelly D, et al. A rapid and high content assay that measures cyto-ID-stained autophagic compartments and estimates autophagy flux with potential clinical applications. Autophagy. 2015;11:560-72 pubmed publisher
    ..The RNAi screen revealed WNK2 and MAP3K6 as autophagy-modulating genes, both of which inhibited the MTOR pathway...
  31. Mazhar A, Jamil F, Bashir Q, Ahmad M, Masood M, Tanvir I, et al. Genetic variants in FGFR2 and TNRC9 genes are associated with breast cancer risk in Pakistani women. Mol Med Rep. 2016;14:3443-51 pubmed publisher
    ..The results of the present study suggest that variants of FGFR2 and TNRC9 may contribute to the genetic susceptibility of BC in Pakistani women. ..
  32. Eapen M, Kota A, Vindin H, McAlinden K, Xenaki D, Oliver B, et al. Apoptosis signal-regulating kinase 1 inhibition attenuates human airway smooth muscle growth and migration in chronic obstructive pulmonary disease. Clin Sci (Lond). 2018;132:1615-1627 pubmed publisher
    ..Collectively, these findings establish the anti-mitogenic effect of ASK1 inhibition and identify a novel pathway that can be targetted to reduce or prevent excessive ASM mass in COPD. ..
  33. Sun H, Kamanova J, Lara Tejero M, Galan J. Salmonella stimulates pro-inflammatory signalling through p21-activated kinases bypassing innate immune receptors. Nat Microbiol. 2018;3:1122-1130 pubmed publisher
    ..These findings illustrate the unique balance that emerges from host-pathogen co-evolution, in that pathogen-initiated responses that help pathogen replication are also important to prevent pathogen spread to deeper tissues. ..
  34. Gaston D, Hansford S, Oliveira C, Nightingale M, Pinheiro H, Macgillivray C, et al. Germline mutations in MAP3K6 are associated with familial gastric cancer. PLoS Genet. 2014;10:e1004669 pubmed publisher
  35. Danai L, Flach R, Virbasius J, Menendez L, Jung D, Kim J, et al. Inducible Deletion of Protein Kinase Map4k4 in Obese Mice Improves Insulin Sensitivity in Liver and Adipose Tissues. Mol Cell Biol. 2015;35:2356-65 pubmed
  36. Fujisawa T, Takahashi M, Tsukamoto Y, Yamaguchi N, Nakoji M, Endo M, et al. The ASK1-specific inhibitors K811 and K812 prolong survival in a mouse model of amyotrophic lateral sclerosis. Hum Mol Genet. 2016;25:245-53 pubmed publisher
    ..These results reinforce the importance of ASK1 as a therapeutic target for ALS treatment. ..
  37. Wang G, Lovato A, Polverari A, Wang M, Liang Y, Ma Y, et al. Genome-wide identification and analysis of mitogen activated protein kinase kinase kinase gene family in grapevine (Vitis vinifera). BMC Plant Biol. 2014;14:219 pubmed publisher
  38. Su Z, Chen D, Zhang E, Li Y, Yu Z, Shi M, et al. MicroRNA-509-3p inhibits cancer cell proliferation and migration by targeting the mitogen-activated protein kinase kinase kinase 8 oncogene in renal cell carcinoma. Mol Med Rep. 2015;12:1535-43 pubmed publisher
    ..Therefore, the results of the present study demonstrated that the miR-509-3p RCC suppressor was a significant regulator of the MAP3K8 oncogene, suggesting that it may have a potential therapeutic role in the treatment of RCC. ..
  39. Lin C, Shih C, Lin Y, Yang Y, Chen B. MEKK1, JNK, and SMAD3 mediate CXCL12-stimulated connective tissue growth factor expression in human lung fibroblasts. J Biomed Sci. 2018;25:19 pubmed publisher
  40. Lafleur E, Kapfer C, Joly V, Liu Y, Tebbji F, Daigle C, et al. The FRK1 mitogen-activated protein kinase kinase kinase (MAPKKK) from Solanum chacoense is involved in embryo sac and pollen development. J Exp Bot. 2015;66:1833-43 pubmed publisher
    ..The ScFRK1 MAPKKK is thus involved in a signalling cascade that regulates both male and female gamete development. ..
  41. Gutmann S, Hinniger A, Fendrich G, Drückes P, Antz S, Mattes H, et al. The Crystal Structure of Cancer Osaka Thyroid Kinase Reveals an Unexpected Kinase Domain Fold. J Biol Chem. 2015;290:15210-8 pubmed publisher
    ..The structurally versatile active site significantly impacts the design of potent, low molecular weight COT kinase inhibitors. ..
  42. Zhang X, Jiang P, Shuai L, Chen K, Li Z, Zhang Y, et al. miR-589-5p inhibits MAP3K8 and suppresses CD90+ cancer stem cells in hepatocellular carcinoma. J Exp Clin Cancer Res. 2016;35:176 pubmed
    ..In HCC, miR-589-5p down-regulates the stemness characteristics of CD90+ CSCs in part by silencing MAP3K8. CD90 and miR-589-5p expression predict HCC outcomes and might be novel molecular targets for HCC treatment. ..
  43. Beck M, Komis G, Ziemann A, Menzel D, Samaj J. Mitogen-activated protein kinase 4 is involved in the regulation of mitotic and cytokinetic microtubule transitions in Arabidopsis thaliana. New Phytol. 2011;189:1069-83 pubmed publisher
    ..In this study, MPK4 is shown to be involved in the regulation of mitosis/cytokinesis through modulation of the cell division plane and cytokinetic progression. ..
  44. Yue J, Xie M, Gou X, Lee P, Schneider M, Wu X. Microtubules regulate focal adhesion dynamics through MAP4K4. Dev Cell. 2014;31:572-85 pubmed publisher
    ..Together, our findings provide critical insight into FA disassembly, suggesting that MTs can deliver MAP4K4 toward FAs through EB2, where MAP4K4 can, in turn, activate Arf6 via IQSEC1 and enhance FA dissolution. ..
  45. Dong P, Xiong Y, Yu J, Chen L, Tao T, Yi S, et al. Control of PD-L1 expression by miR-140/142/340/383 and oncogenic activation of the OCT4-miR-18a pathway in cervical cancer. Oncogene. 2018;37:5257-5268 pubmed publisher
    ..Loss of miR-140/142/340/383 contributes to PD-L1 upregulation. miR-18a enhances PD-L1 levels by targeting PTEN, WNK2 (ERK1/2 pathway inhibitor), and SOX6 (Wnt/β-catenin pathway inhibitor and p53 pathway activator) to activate the ..
  46. Cordas Dos Santos D, Eilers J, Sosa Vizcaino A, Orlova E, Zimmermann M, Stanulla M, et al. MAP3K7 is recurrently deleted in pediatric T-lymphoblastic leukemia and affects cell proliferation independently of NF-κB. BMC Cancer. 2018;18:663 pubmed publisher
    ..Homozygous deletions of MAP3K7 were not observed, and efficient depletion of MAP3K7 interfered with viability of T-ALL cells, indicating that a residual expression of MAP3K7 is indispensable for T-lymphoblasts. ..
  47. Li W, Xu H, Liu Y, Song L, Guo C, Shu Y. Bioinformatics Analysis of MAPKKK Family Genes in Medicago truncatula. Genes (Basel). 2016;7: pubmed publisher
    ..In summary, our genome-wide, systemic characterization and expressional analysis of MtMAPKKK genes will provide insights that will be useful for characterizing the molecular functions of these genes in M. truncatula. ..
  48. Wood M, Rios D, Williams I. TNF-? augments RANKL-dependent intestinal M cell differentiation in enteroid cultures. Am J Physiol Cell Physiol. 2016;311:C498-507 pubmed publisher
  49. Wood K, Konieczkowski D, Johannessen C, Boehm J, Tamayo P, Botvinnik O, et al. MicroSCALE screening reveals genetic modifiers of therapeutic response in melanoma. Sci Signal. 2012;5:rs4 pubmed publisher
  50. Sheu M, Chiang C, Su H, Chen C, Sheehan J, Pan H. Intrathecal Injection of Dual Zipper Kinase shRNA Alleviating the Neuropathic Pain in a Chronic Constrictive Nerve Injury Model. Int J Mol Sci. 2018;19: pubmed publisher
    ..The modulation of DLK expression is a potential clinic treatment option for neuropathic pain. ..
  51. Tan L, Nomanbhoy T, Gurbani D, PATRICELLI M, Hunter J, Geng J, et al. Discovery of type II inhibitors of TGFβ-activated kinase 1 (TAK1) and mitogen-activated protein kinase kinase kinase kinase 2 (MAP4K2). J Med Chem. 2015;58:183-96 pubmed publisher
    ..A 2.4 Ã… cocrystal structure of TAK1 in complex with 1 confirms that the activation loop of TAK1 assumes the DFG-out conformation characteristic of type II inhibitors. ..
  52. Song J, Cheon S, Lee W, Park K, Lee J. The effect of ASK1 on vascular permeability and edema formation in cerebral ischemia. Brain Res. 2015;1595:143-55 pubmed publisher
    ..Based on our findings, we propose that ASK1 is a regulating factor of vascular permeability and edema formation in cerebral ischemia. ..
  53. Couto J, Vivero M, Kozakewich H, Taghinia A, Mulliken J, Warman M, et al. A somatic MAP3K3 mutation is associated with verrucous venous malformation. Am J Hum Genet. 2015;96:480-6 pubmed publisher
    ..Studies using global and conditional Map3k3 knockout mice have previously implicated MAP3K3 in vascular development. MAP3K3 dysfunction probably causes VVM in humans. ..
  54. Kumar A, Zhang K. Prospective evaluation of shape similarity based pose prediction method in D3R Grand Challenge 2015. J Comput Aided Mol Des. 2016;30:685-693 pubmed
    ..pose prediction method was used to predict binding poses of heat shock protein 90 (HSP90) and mitogen activated protein kinase kinase kinase kinase (MAP4K4) ligands and it was able to predict the pose within 2 Å root mean square ..
  55. Muthaiyan Shanmugam M, Bhan P, Huang H, Hsieh J, Hua T, Wu G, et al. Cilium Length and Intraflagellar Transport Regulation by Kinases PKG-1 and GCK-2 in Caenorhabditis elegans Sensory Neurons. Mol Cell Biol. 2018;38: pubmed publisher
    ..Importantly, transmission electron microscopy (TEM) analysis revealed no structural changes in cilia of pkg-1 and gck-2 mutants. ..
  56. Ji C, Wang Y, Xiang D, Liu Q, Zhou Z, Qian F, et al. Kir2.1 Interaction with Stk38 Promotes Invasion and Metastasis of Human Gastric Cancer by Enhancing MEKK2-MEK1/2-ERK1/2 Signaling. Cancer Res. 2018;78:3041-3053 pubmed publisher
    ..1 contributes to invasion and metastasis by a noncanonical ion permeation-independent signaling pathway and may act as a novel prognostic marker and therapeutic target for gastric cancer. Cancer Res; 78(11); 3041-53. ©2018 AACR. ..
  57. Virk N, Li D, Tian L, Huang L, Hong Y, Li X, et al. Arabidopsis Raf-Like Mitogen-Activated Protein Kinase Kinase Kinase Gene Raf43 Is Required for Tolerance to Multiple Abiotic Stresses. PLoS ONE. 2015;10:e0133975 pubmed publisher
    ..cinerea or Pseudomonas syringae pv. tomato DC3000. Our results demonstrate that Raf43, encoding for a Raf-like MAPKKK, is required for tolerance to multiple abiotic stresses in Arabidopsis. ..
  58. Ma X, Chen Y, Zhang S, Xu W, Shao Y, Yang Y, et al. Rho1-Wnd signaling regulates loss-of-cell polarity-induced cell invasion in Drosophila. Oncogene. 2016;35:846-55 pubmed publisher
    ..Together, our data not only provides a novel mechanistic insight on how cell polarity loss contributes to cell invasion, but also highlights the value of the Drosophila model system to explore human cancer biology. ..
  59. Li T, Qiao H, Tong H, Zhuang T, Wang T. Association of Common Genetic Variants in Mitogen-activated Protein Kinase Kinase Kinase Kinase 4 with Type 2 Diabetes Mellitus in a Chinese Han Population. Chin Med J (Engl). 2016;129:1179-84 pubmed publisher
    ..045) and homeostatic model assessment-insulin resistance (P = 0.037). MAP4K4 gene is associated with T2DM in a Chinese Han population, and MAP4K4 gene variants may contribute to the risk toward the development of T2DM. ..
  60. Pleinis J, Davis C, Cantrell C, Qiu D, Zhan X. Purification, auto-activation and kinetic characterization of apoptosis signal-regulating kinase I. Protein Expr Purif. 2017;132:34-43 pubmed publisher
    ..This study provides novel mechanistic and kinetic insights into the ASK1-initiated MAPK signal transduction via highly controlled reconstructed protein systems. ..
  61. Lee J, Jeong S, Park J, Lee C, Ku C, Kang S, et al. Aberrant expression of COT is related to recurrence of papillary thyroid cancer. Medicine (Baltimore). 2015;94:e548 pubmed publisher
    ..0001, FDR q-value = 0.000).Aberrant expression of A-, B-, and C-RAF, and COT is frequent in PTC; increased expression of COT is correlated with recurrence of PTC. ..
  62. Noro T, Namekata K, Kimura A, Guo X, Azuchi Y, Harada C, et al. Spermidine promotes retinal ganglion cell survival and optic nerve regeneration in adult mice following optic nerve injury. Cell Death Dis. 2015;6:e1720 pubmed publisher
    ..Our findings indicate that spermidine stimulates neuroprotection as well as neuroregeneration, and may be useful for treatment of various neurodegenerative diseases including glaucoma. ..
  63. Zhang X, Mi X, Chen C, Wang H, Guo W. Identification on mitogen-activated protein kinase signaling cascades by integrating protein interaction with transcriptional profiling analysis in cotton. Sci Rep. 2018;8:8178 pubmed publisher
  64. Piala A, Akella R, Potts M, Dudics Giagnocavo S, He H, Wei S, et al. Discovery of novel TAOK2 inhibitor scaffolds from high-throughput screening. Bioorg Med Chem Lett. 2016;26:3923-7 pubmed publisher
    The MAP3K (Mitogen Activated Protein Kinase Kinase Kinase) TAOK2 (Thousand-And-One Kinase 2) is an activator of p38 MAP kinase cascade that is up-regulated in response to environmental stresses...
  65. Yamada S, Noguchi H, Tanimoto A. Critical and diverse in vivo roles of apoptosis signal-regulating kinase 1 in animal models of atherosclerosis and cholestatic liver injury. Histol Histopathol. 2017;32:433-444 pubmed publisher
    ..We herein review the diverse, key in vivo roles of ASK1 signaling in the pathogenesis of inflammatory disorders closely related to metabolic syndrome. ..
  66. Miura T, Matsuo A, Muraoka T, Ide M, Morikami K, Kamikawa T, et al. Identification of a selective inhibitor of transforming growth factor ?-activated kinase 1 by biosensor-based screening of focused libraries. Bioorg Med Chem Lett. 2017;27:1031-1036 pubmed publisher
    ..The effort resulted in the identification of a new TAK1-selective Type I compound with a thienopyrimidine scaffold that served as a good starting point for medicinal chemistry. ..
  67. Neoh C, Wu W, Dai G, Su J, Liu C, Su T, et al. Flaccidoxide-13-Acetate Extracted from the Soft Coral Cladiella kashmani Reduces Human Bladder Cancer Cell Migration and Invasion through Reducing Activation of the FAK/PI3K/AKT/mTOR Signaling Pathway. Molecules. 2017;23: pubmed publisher
    ..In conclusion, our study was the first to demonstrate that flaccidoxide-13-acetate could be a potent medical agent for use in controlling the migration and invasion of bladder cancer. ..
  68. Yao L, Ye Y, Mao H, Lu F, He X, Lu G, et al. MicroRNA-124 regulates the expression of MEKK3 in the inflammatory pathogenesis of Parkinson's disease. J Neuroinflammation. 2018;15:13 pubmed publisher
  69. Sumiya E, Negishi Koga T, Nagai Y, Suematsu A, Suda T, Shinohara M, et al. Phosphoproteomic analysis of kinase-deficient mice reveals multiple TAK1 targets in osteoclast differentiation. Biochem Biophys Res Commun. 2015;463:1284-90 pubmed publisher
    ..Thus, TAK1 functions as a critical regulator of the phosophorylation status of various cellular proteins that govern osteoclastogenesis. ..
  70. Roth Flach R, Skoura A, Matevossian A, Danai L, Zheng W, Cortes C, et al. Endothelial protein kinase MAP4K4 promotes vascular inflammation and atherosclerosis. Nat Commun. 2015;6:8995 pubmed publisher
    ..Taken together, these results reveal that MAP4K4 is a key signalling node that promotes immune cell recruitment in atherosclerosis. ..
  71. Bullard S, Seo S, Schilling B, Dyle M, Dierdorff J, Ebert S, et al. Gadd45a Protein Promotes Skeletal Muscle Atrophy by Forming a Complex with the Protein Kinase MEKK4. J Biol Chem. 2016;291:17496-17509 pubmed publisher
    ..Together, these results identify a direct biochemical mechanism by which Gadd45a induces skeletal muscle atrophy and provide new insight into the way that skeletal muscle atrophy occurs at the molecular level. ..
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    ..All data reveal that miR-188 induces lin-BMC senescence by targeting MAP3K3 expression, thus, providing new theoretical basis for the prevention and treatment of cardiovascular diseases. ..
  74. Wang X, Hou Y, Deng K, Zhang Y, Wang D, Ding J. Structural Insights into the Molecular Recognition between Cerebral Cavernous Malformation 2 and Mitogen-Activated Protein Kinase Kinase Kinase 3. Structure. 2015;23:1087-96 pubmed publisher
    ..These findings build a structural framework for understanding CCM2ct-MEKK3 molecular recognition. ..
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    ..In several types of cancer, MLK3 signaling is implicated in promoting cell proliferation, as well as driving cell migration, invasion and metastasis. ..
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    ..These results provide useful information regarding the influence of MAP3K5 on RFI in pigs. ..
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    ..b>Implications: On the basis of these findings, MLK3 emerges as a potential therapeutic target for the treatment of glioblastoma. Mol Cancer Res; 15(8); 1085-95. ©2017 AACR. ..
  78. Meng L, Xu M, Li D, Zhou M, Jiang J. Soluble Sugar Accumulation Can Influence Seed Size via AN3-YDA Gene Cascade. J Agric Food Chem. 2017;65:4121-4132 pubmed publisher
    ..Our findings guide the synthesis of a model that predicts the integration of soluble sugar accumulation at AN3 to control the establishment of seed size. ..
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  80. Li L, Ye C, Zhao R, Li X, Liu W, Wu F, et al. Mitogen-activated protein kinase kinase kinase (MAPKKK) 4 from rapeseed (Brassica napus L.) is a novel member inducing ROS accumulation and cell death. Biochem Biophys Res Commun. 2015;467:792-7 pubmed publisher
    ..Further investigation identified BnaMAPKKK4 elicited ROS through the downstream MPK3. These results indicate that BnaMAPKKK4 and its downstream components function in the ROS-induced cell death. ..
  81. Chen X, Zhou J, Luo L, Han B, Li F, Chen J, et al. Black Rice Anthocyanins Suppress Metastasis of Breast Cancer Cells by Targeting RAS/RAF/MAPK Pathway. Biomed Res Int. 2015;2015:414250 pubmed publisher
    ..In summary, our study suggested that BRACs suppress metastasis in breast cancer cells by targeting the RAS/RAF/MAPK pathway. ..
  82. Jia W, Dong Y, Tao L, Pang L, Ren Y, Liang W, et al. MAP3K3 overexpression is associated with poor survival in ovarian carcinoma. Hum Pathol. 2016;50:162-9 pubmed publisher
    ..All these findings suggested that MAP3K3 overexpression is an independent poor prognostic indicator of OC and can be a clinically effective biomarker of OC. ..
  83. Hirata Y, Takahashi M, Morishita T, Noguchi T, Matsuzawa A. Post-Translational Modifications of the TAK1-TAB Complex. Int J Mol Sci. 2017;18: pubmed publisher
    ..This review therefore focuses on recent advances in the understanding of the PTMs of the TAK1-TAB complex. ..
  84. Yang T, Zhao K, Shu H, Chen X, Cheng J, Li S, et al. The Nogo receptor inhibits proliferation, migration and axonal extension by transcriptionally regulating WNK1 in PC12 cells. Neuroreport. 2017;28:533-539 pubmed publisher
    ..or knockdown of NgR, and the regulation is specific to WNK1, which is not the same for its family members, WNK2, WNK3 and WNK4...
  85. Wu H, Zhou J, Ou W, Li Y, Liu M, Yang C. TAK1 as the mediator in the protective effect of propofol on renal interstitial fibrosis induced by ischemia/reperfusion injury. Eur J Pharmacol. 2017;811:134-140 pubmed publisher
    ..Collectively, our results validated that propofol could ameliorate the IRI-induced renal interstitial fibrosis in mice by downregulation of TAK1 and inhibition of apoptosis at the early stage. ..
  86. Byrnes K, Phatak P, Mansour D, Xiao L, Zou T, Rao J, et al. Overexpression of miR-199a-5p decreases esophageal cancer cell proliferation through repression of mitogen-activated protein kinase kinase kinase-11 (MAP3K11). Oncotarget. 2016;7:8756-70 pubmed publisher
    ..These findings suggest that miR-199a-5p acts as a tumor suppressor in esophageal cancer cells and that its downregulation contributes to enhanced cellular proliferation by targeting MAP3K11. ..
  87. Yuan F, Chen Y, Zhang Z, Yue H, Bi H, Yuan K, et al. Down-regulation apoptosis signal-regulating kinase 1 gene reduced the Litopenaeus vannamei hemocyte apoptosis in WSSV infection. Fish Shellfish Immunol. 2016;50:109-16 pubmed publisher
    ..vannamei. These results suggested that down-regulation of LvASK1 decreased the apoptotic rate of hemocytes in WSSV-infected shrimp, and that it could contribute to the reduction of cumulative mortality in WSSV-infected L. vannamei. ..
  88. Körber M, Staribacher A, Ratzenböck I, Steger G, Mader R. NF?B-Associated Pathways in Progression of Chemoresistance to 5-Fluorouracil in an In Vitro Model of Colonic Carcinoma. Anticancer Res. 2016;36:1631-9 pubmed
    ..The efficacy of MAP3K8 inhibition in our model potentially uncovers a new mechanism to circumvent 5-FU resistance. ..
  89. Galani V, Lampri E, Varouktsi A, Alexiou G, Mitselou A, Kyritsis A. Genetic and epigenetic alterations in meningiomas. Clin Neurol Neurosurg. 2017;158:119-125 pubmed publisher
    ..of the tumor suppressor genes p73 in grade I meningiomas and TIMP3 GSTP1, MEG3, HOXA6, HOXA9, PENK, WNK2 and UPK3A genes with an increasing frequency according to grade...
  90. Roth Flach R, DiStefano M, Danai L, Senol Cosar O, Yawe J, Kelly M, et al. Map4k4 impairs energy metabolism in endothelial cells and promotes insulin resistance in obesity. Am J Physiol Endocrinol Metab. 2017;313:E303-E313 pubmed publisher
  91. Liu Y, Qu G, Lu Y, Kong W, Liu Y, Chen W, et al. Silencing of MAP4K4 by short hairpin RNA suppresses proliferation, induces G1 cell cycle arrest and induces apoptosis in gastric cancer cells. Mol Med Rep. 2016;13:41-8 pubmed publisher
    ..In addition, Notch signaling was markedly reduced by MAP4K4 silencing. The results of the present study suggested that inhibition of MAP4K4 may be a therapeutic strategy for GC. ..
  92. Sai K, Morioka S, Takaesu G, Muthusamy N, Ghashghaei H, Hanafusa H, et al. TAK1 determines susceptibility to endoplasmic reticulum stress and leptin resistance in the hypothalamus. J Cell Sci. 2016;129:1855-65 pubmed publisher
    ..Thus, TAK1 is a crucial regulator of ER stress in vivo, which could be a target for alleviation of ER stress and its associated disease conditions. ..