MEKK1

Summary

Gene Symbol: MEKK1
Description: mitogen-activated protein kinase kinase kinase 1
Alias: MAPKKK1, MEKK, MEKK 1, MEKK1, SRXY6, mitogen-activated protein kinase kinase kinase 1, MAP/ERK kinase kinase 1, MAPK/ERK kinase kinase 1, MEK kinase 1, mitogen-activated protein kinase kinase kinase 1, E3 ubiquitin protein ligase
Species: human
Products:     MEKK1

Top Publications

  1. Yujiri T, Sather S, Fanger G, Johnson G. Role of MEKK1 in cell survival and activation of JNK and ERK pathways defined by targeted gene disruption. Science. 1998;282:1911-4 pubmed
    Targeted disruption of the gene encoding MEK kinase 1 (MEKK1), a mitogen-activated protein kinase (MAPK) kinase kinase, defined its function in the regulation of MAPK pathways and cell survival...
  2. Mokhtari D, Myers J, Welsh N. MAPK kinase kinase-1 is essential for cytokine-induced c-Jun NH2-terminal kinase and nuclear factor-kappaB activation in human pancreatic islet cells. Diabetes. 2008;57:1896-904 pubmed publisher
    ..The aim of the present investigation was to elucidate a putative role of the MAPK kinase kinase-1 (MEKK-1) in cytokine-induced signaling...
  3. Vinik B, Kay E, Fiedorek F. Mapping of the MEK kinase gene (Mekk) to mouse chromosome 13 and human chromosome 5. Mamm Genome. 1995;6:782-3 pubmed
  4. Garcia Closas M, Hall P, Nevanlinna H, Pooley K, Morrison J, Richesson D, et al. Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics. PLoS Genet. 2008;4:e1000054 pubmed publisher
    ..Understanding the etiologic heterogeneity of breast cancer may ultimately result in improvements in prevention, early detection, and treatment. ..
  5. Barnholtz Sloan J, Shetty P, Guan X, Nyante S, Luo J, Brennan D, et al. FGFR2 and other loci identified in genome-wide association studies are associated with breast cancer in African-American and younger women. Carcinogenesis. 2010;31:1417-23 pubmed publisher
    ..These results highlight the need to conduct GWAS among younger women and in a variety of racial-ethnic populations. ..
  6. Lu P, Yang J, Li C, Wei M, Shen W, Shi L, et al. Association between mitogen-activated protein kinase kinase kinase 1 rs889312 polymorphism and breast cancer risk: evidence from 59,977 subjects. Breast Cancer Res Treat. 2011;126:663-70 pubmed publisher
  7. Pearlman A, Loke J, Le Caignec C, White S, Chin L, Friedman A, et al. Mutations in MAP3K1 cause 46,XY disorders of sex development and implicate a common signal transduction pathway in human testis determination. Am J Hum Genet. 2010;87:898-904 pubmed publisher
    ..Thus, mutations in MAP3K1 that result in 46,XY DSD with partial or complete gonadal dysgenesis implicate this pathway in normal human sex determination. ..
  8. Schlesinger T, Bonvin C, Jarpe M, Fanger G, Cardinaux J, Johnson G, et al. Apoptosis stimulated by the 91-kDa caspase cleavage MEKK1 fragment requires translocation to soluble cellular compartments. J Biol Chem. 2002;277:10283-91 pubmed
    b>MEKK1, a 196-kDa mitogen-activated protein kinase (MAPK) kinase kinase, generates anti-apoptotic signaling as a full-length protein but induces apoptosis when cleaved by caspases...
  9. Chadee D, Yuasa T, Kyriakis J. Direct activation of mitogen-activated protein kinase kinase kinase MEKK1 by the Ste20p homologue GCK and the adapter protein TRAF2. Mol Cell Biol. 2002;22:737-49 pubmed
    ..Recombinant forms of MAP3K MEK kinase 1 (MEKK1) interact in vivo and in vitro with the STE20 protein homologue germinal center kinase (GCK), and both ..

More Information

Publications106 found, 100 shown here

  1. Gallagher E, Gutowski S, Sternweis P, Cobb M. RhoA binds to the amino terminus of MEKK1 and regulates its kinase activity. J Biol Chem. 2004;279:1872-7 pubmed
    b>MEKK1 is a mitogen-activated protein kinase kinase kinase (MAP3K) that can regulate the c-Jun amino-terminal kinase (JNK) MAP kinase cascade. MEKK1 is comprised of a kinase domain and a long amino-terminal regulatory domain...
  2. Latif A, Hadfield K, Roberts S, Shenton A, Lalloo F, Black G, et al. Breast cancer susceptibility variants alter risks in familial disease. J Med Genet. 2010;47:126-31 pubmed publisher
    ..The level of risk is dependent on the strength of the family history and the presence of a BRCA1/2 mutation and contributes to the understanding of the use of these variants in clinical risk prediction. ..
  3. Jara L, Gonzalez Hormazabal P, Cerceño K, Di Capua G, Reyes J, Blanco R, et al. Genetic variants in FGFR2 and MAP3K1 are associated with the risk of familial and early-onset breast cancer in a South-American population. Breast Cancer Res Treat. 2013;137:559-69 pubmed publisher
    ..Nevertheless, there is no evidence of an interaction between FGFR2 ht2 and the MAP3K1 rs889312 C allele. These findings suggest that genetic variants in the FGFR2 and MAP3K1 genes may contribute to genetic susceptibility to BC. ..
  4. Resler A, Malone K, Johnson L, Malkki M, Petersdorf E, McKnight B, et al. Genetic variation in TLR or NFkappaB pathways and the risk of breast cancer: a case-control study. BMC Cancer. 2013;13:219 pubmed publisher
    ..Given the few suggestive associations in our data and the compelling biologic rationale for an association between genetic variation in these pathways and breast cancer risk, further studies are warranted that examine these effects. ..
  5. Lu Z, Xu S, Joazeiro C, Cobb M, Hunter T. The PHD domain of MEKK1 acts as an E3 ubiquitin ligase and mediates ubiquitination and degradation of ERK1/2. Mol Cell. 2002;9:945-56 pubmed
    ..The PHD domain of MEKK1, a RING finger-like structure, exhibited E3 ubiquitin ligase activity toward ERK2 in vitro and in vivo...
  6. Easton D, Pooley K, Dunning A, Pharoah P, Thompson D, Ballinger D, et al. Genome-wide association study identifies novel breast cancer susceptibility loci. Nature. 2007;447:1087-93 pubmed
    ..05 level compared with an estimated 1,343 that would be expected by chance, indicating that many additional common susceptibility alleles may be identifiable by this approach. ..
  7. Huijts P, Vreeswijk M, Kroeze Jansema K, Jacobi C, Seynaeve C, Krol Warmerdam E, et al. Clinical correlates of low-risk variants in FGFR2, TNRC9, MAP3K1, LSP1 and 8q24 in a Dutch cohort of incident breast cancer cases. Breast Cancer Res. 2007;9:R78 pubmed
    ..These findings provide interesting new clues for further research on these low-risk susceptibility alleles. ..
  8. Thomas G, Jacobs K, Kraft P, Yeager M, Wacholder S, Cox D, et al. A multistage genome-wide association study in breast cancer identifies two new risk alleles at 1p11.2 and 14q24.1 (RAD51L1). Nat Genet. 2009;41:579-84 pubmed publisher
    ..1 (rs999737; P = 1.74 x 10(-7)) localizes to RAD51L1, a gene in the homologous recombination DNA repair pathway. We also confirmed associations with loci on chromosomes 2q35, 5p12, 5q11.2, 8q24, 10q26 and 16q12.1. ..
  9. Turnbull C, Ahmed S, Morrison J, Pernet D, Renwick A, Maranian M, et al. Genome-wide association study identifies five new breast cancer susceptibility loci. Nat Genet. 2010;42:504-7 pubmed publisher
  10. Xu S, Cobb M. MEKK1 binds directly to the c-Jun N-terminal kinases/stress-activated protein kinases. J Biol Chem. 1997;272:32056-60 pubmed
    ..b>MEKK1 has been shown to be a strong activator of the c-Jun N-terminal kinase/stress-actived protein kinase (JNK/SAPK) ..
  11. Witowsky J, Johnson G. Ubiquitylation of MEKK1 inhibits its phosphorylation of MKK1 and MKK4 and activation of the ERK1/2 and JNK pathways. J Biol Chem. 2003;278:1403-6 pubmed
    b>MEKK1 is a MAPK kinase kinase that is activated in response to stimuli that alter the cytoskeleton and cell shape. MEKK1 phosphorylates and activates MKK1 and MKK4, leading to ERK1/2 and JNK activation...
  12. Mokhtari D, Myers J, Welsh N. The MAPK kinase kinase-1 is essential for stress-induced pancreatic islet cell death. Endocrinology. 2008;149:3046-53 pubmed publisher
    The aim of the present investigation was to characterize the role of the MAPK kinase kinase-1 (MEKK-1) in stress-induced cell death of insulin producing cells...
  13. Rebbeck T, DeMichele A, Tran T, Panossian S, Bunin G, Troxel A, et al. Hormone-dependent effects of FGFR2 and MAP3K1 in breast cancer susceptibility in a population-based sample of post-menopausal African-American and European-American women. Carcinogenesis. 2009;30:269-74 pubmed publisher
    ..We further report that these genes confer their effects in HER2- tumors, interact with one another to confer breast cancer susceptibility in AA women and interact with hormone exposures in AA and EA women...
  14. Wang N, Cao Y, Zhu Y. Netrin-1 prevents the development of cardiac hypertrophy and heart failure. Mol Med Rep. 2016;13:2175-81 pubmed publisher
    ..Therefore, netrin‑1 prevented cardiac hypertrophy and heart failure through the negative regulation of the MEKK1-dependent MEK‑ERK1/2 and JNK1/2 signaling pathways.
  15. Xiao N, Li H, Yu W, Gu C, Fang H, Peng Y, et al. SUMO-specific protease 2 (SENP2) suppresses keratinocyte migration by targeting NDR1 for de-SUMOylation. FASEB J. 2019;33:163-174 pubmed publisher
    ..NDR1 on Lys-465 attenuates its inhibition of p38/ERK1/2 activation by decreasing the association of NDR1 with MEK kinase 1/2...
  16. Xing Y, Chen W, Jia W, Zhang J. Mitogen-activated protein kinase kinase 5 (MKK5)-mediated signalling cascade regulates expression of iron superoxide dismutase gene in Arabidopsis under salinity stress. J Exp Bot. 2015;66:5971-81 pubmed publisher
    ..MKK5 interacted with the MEKK1 protein that was also involved in the salt-induced FSD signalling pathway...
  17. Lu F, Wikramasinghe P, Norseen J, Tsai K, Wang P, Showe L, et al. Genome-wide analysis of host-chromosome binding sites for Epstein-Barr Virus Nuclear Antigen 1 (EBNA1). Virol J. 2010;7:262 pubmed publisher
    ..We conclude that EBNA1 can interact with a large number of cellular genes and chromosomal loci in latently infected cells, but that these sites are likely to represent a complex ensemble of direct and indirect EBNA1 binding sites. ..
  18. Robertson R, Guihéneuf F, Bahar B, Schmid M, Stengel D, Fitzgerald G, et al. The Anti-Inflammatory Effect of Algae-Derived Lipid Extracts on Lipopolysaccharide (LPS)-Stimulated Human THP-1 Macrophages. Mar Drugs. 2015;13:5402-24 pubmed publisher
    ..dioica and C. crispus can inhibit LPS-induced inflammatory pathways in human macrophages. Therefore, algal lipid extracts should be further explored as anti-inflammatory ingredients for chronic inflammation-linked metabolic diseases. ..
  19. Wu L, Liu C, Jiang M, Jiang Y, Wang Q, Lu Z, et al. Defective eyelid leading edge cell migration in C57BL/6-corneal opacity mice with an "eye open at birth" phenotype. Genet Mol Res. 2016;15: pubmed publisher
    ..Abnormal keratinocyte migration and down-regulated expression of the Hbegf gene might be associated with impaired eyelid development in B6-Co mice. ..
  20. Bian Y, Qin C, Xin Y, Yu Y, Chen H, Wang G, et al. Itraq-Based Quantitative Proteomic Analysis of Lungs in Murine Polymicrobial Sepsis with Hydrogen Gas Treatment. Shock. 2018;49:187-195 pubmed publisher
    ..Thus, our findings provide an insight into the mechanism of H2 treatment in sepsis by proteomic approach, which may be helpful to the clinic application of H2 in patients with sepsis. ..
  21. Bai M, Ma X, Li X, Wang X, Mei Q, Li X, et al. The Accomplices of NF-?B Lead to Radioresistance. Curr Protein Pept Sci. 2015;16:279-94 pubmed
    ..mechanisms of IR in NF-?B activation, such as ROS/NF-?B, ATM or DNA-PK/MAPKK/ p90rsk, PI3K/AKT/IKK and k-ras/c-raf/ MEKK/ NF-?B pathways. Moreover, we describe how the expression of the target genes (e.g...
  22. Sang M, Li C, Wu W, Li B. Identification and evolution of two insulin receptor genes involved in Tribolium castaneum development and reproduction. Gene. 2016;585:196-204 pubmed publisher
    ..2%. Moreover, RNAi against these two genes increased the expression of the pkc, foxo, jnk, cdc42, ikk, and mekk genes but decreased erk gene expression...
  23. Tong L, Hou A, Wong T. Altered expression level of inflammation-related genes and long-term changes in ocular surface after trabeculectomy, a prospective cohort study. Ocul Surf. 2018;: pubmed publisher
    ..Glaucoma surgery may confer long term beneficial effect on the ocular surface, if anti-glaucoma eyedrops are no longer necessary. This may be due to reduced expression of conjunctival proinflammatory genes and immune-related genes. ..
  24. Haider M, Kurjogi M, Khalil Ur Rehman M, Fiaz M, Pervaiz T, Jiu S, et al. Grapevine immune signaling network in response to drought stress as revealed by transcriptomic analysis. Plant Physiol Biochem. 2017;121:187-195 pubmed publisher
    ..calcium signals, protein phosphatase 2C, calcineurin B-like proteins, MAPKs, and phosphorylation (FLS2 and MEKK1) cascades were up-regulated in response to drought stress...
  25. Guan Y, Liang G, Martin G, Guan L. Functional changes in mRNA expression and alternative pre-mRNA splicing associated with the effects of nutrition on apoptosis and spermatogenesis in the adult testis. BMC Genomics. 2017;18:64 pubmed publisher
    ..However, more research is required to verify their causal effects in regulating spermatogenesis and germ cell apoptosis. ..
  26. 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...
  27. Chen X, Zhu X, Liu Y, Lv Q, Ma J. Silencing of Phospholipase C gamma 2 Promotes Proliferation of Rat Hepatocytes In Vitro. J Cell Biochem. 2017;: pubmed publisher
    ..suppression of PLC?2 gene expression could cause the caspase dependent cell death by inhibiting the signal pathway MEKK1/MKK4/JNK1/2/c-Jun...
  28. Esposito S, Ierardi V, Daleno C, Scala A, Terranova L, Tagliabue C, et al. Genetic polymorphisms and risk of recurrent wheezing in pediatric age. BMC Pulm Med. 2014;14:162 pubmed publisher
    ..Although further studies are needed to confirm the results, these findings may be useful for the early identification of children at the highest risk of developing recurrent episodes and possibly subsequent asthma. ..
  29. Gyorffy B, Pongor L, Bottai G, Li X, Budczies J, Szabo A, et al. An integrative bioinformatics approach reveals coding and non-coding gene variants associated with gene expression profiles and outcome in breast cancer molecular subtypes. Br J Cancer. 2018;118:1107-1114 pubmed publisher
    ..Our data provide potential opportunities to identify non-coding variations with functional and clinical relevance in breast cancer. ..
  30. Fu M, Wang C, Wang J, Zhang X, Sakamaki T, Yeung Y, et al. Androgen receptor acetylation governs trans activation and MEKK1-induced apoptosis without affecting in vitro sumoylation and trans-repression function. Mol Cell Biol. 2002;22:3373-88 pubmed
    ..functions including secondary sexual differentiation in the male and the induction of apoptosis by the JNK kinase, MEKK1. The AR is posttranslationally modified on lysine residues by acetylation and sumoylation...
  31. Thiaville M, Pan Y, Gjymishka A, Zhong C, Kaufman R, Kilberg M. MEK signaling is required for phosphorylation of eIF2alpha following amino acid limitation of HepG2 human hepatoma cells. J Biol Chem. 2008;283:10848-57 pubmed publisher
    ..Collectively, these results document a critical interdependence between the MEK-ERK MAPK signaling pathway and the amino acid stress-activated pathway. ..
  32. Bowes J, Potter C, Gibbons L, Hyrich K, Plant D, Morgan A, et al. Investigation of genetic variants within candidate genes of the TNFRSF1B signalling pathway on the response to anti-TNF agents in a UK cohort of rheumatoid arthritis patients. Pharmacogenet Genomics. 2009;19:319-23 pubmed publisher
    ..We conclude that analysis of the common variation in the selected candidate genes did not provide strong evidence to implicate their involvement in varying patient response to anti-TNF treatment. ..
  33. Odefrey F, Stone J, Gurrin L, Byrnes G, Apicella C, Dite G, et al. Common genetic variants associated with breast cancer and mammographic density measures that predict disease. Cancer Res. 2010;70:1449-58 pubmed publisher
    ..These findings could help elucidate how those variants and mammographic density measures are associated with breast cancer susceptibility. ..
  34. Leissing F, Nomoto M, Bocola M, Schwaneberg U, Tada Y, Conrath U, et al. Substrate thiophosphorylation by Arabidopsis mitogen-activated protein kinases. BMC Plant Biol. 2016;16:48 pubmed publisher
    ..MPK cascades function via reversible phosphorylation of cascade components, MEKK, MEK, and MPK, but also by MPK substrate phosphorylation...
  35. Loke J, Pearlman A, Radi O, Zuffardi O, Giussani U, Pallotta R, et al. Mutations in MAP3K1 tilt the balance from SOX9/FGF9 to WNT/?-catenin signaling. Hum Mol Genet. 2014;23:1073-83 pubmed publisher
    ..Although MAP3K1 is not usually required for testis determination, mutations in this gene can disrupt normal development through the gains of function demonstrated in this study. ..
  36. Sylvain Prévost S, Ear T, Simard F, Fortin C, Dubois C, Flamand N, et al. Activation of TAK1 by Chemotactic and Growth Factors, and Its Impact on Human Neutrophil Signaling and Functional Responses. J Immunol. 2015;195:5393-403 pubmed publisher
    ..Inhibition of TAK1 also impaired MEKK3 (but not MEKK1) activation by fMLF...
  37. Yue J, López J. JNK does not regulate meiotic progression in Xenopus oocytes: The strange case of pJNK and pERK. Dev Biol. 2016;416:42-51 pubmed publisher
    ..The serine/threonine kinase MEKK1, an upstream activator of JNK and p38, is activated during stress conditions and regulates apoptosis in different ..
  38. Huang Z, Lien G, Lin C, Jiang C, Chen B. p300 and C/EBP?-regulated IKK? expression are involved in thrombin-induced IL-8/CXCL8 expression in human lung epithelial cells. Pharmacol Res. 2017;121:33-41 pubmed publisher
    ..c-Src-dependent I?B kinase (IKK)/I?B?/nuclear factor (NF)-?B and mitogen-activated protein kinase kinase kinase 1 (MEKK1)/extracellular signal-regulated kinase (ERK)/ribosomal S6 protein kinase (RSK)-dependent CAAT/enhancer-binding ..
  39. Spagnoli A, Borsellino A, Crucianelli S, Bizzarri C, Mucciolo M, Trucchi A, et al. Complete Scrotal Agenesis: New Surgical Approach Using Self-inflating Tissue Expander. Urology. 2018;112:169-171 pubmed publisher
    ..By constant and gradual expansion, self-inflating prothesis avoids patient discomfort and facilitates orchiopexy. ..
  40. Cuenda A, Dorow D. Differential activation of stress-activated protein kinase kinases SKK4/MKK7 and SKK1/MKK4 by the mixed-lineage kinase-2 and mitogen-activated protein kinase kinase (MKK) kinase-1. Biochem J. 1998;333 ( Pt 1):11-5 pubmed
    ..of the protein kinases mixed-lineage kinase-2 (MLK2) or mitogen-activated protein kinase (MAPK) kinase kinase-1 (MEKK1) is known to trigger the activation of stress-activated protein kinase (SAPK1)/c-Jun N-terminal kinase (JNK)...
  41. Zhou L, Tan A, Iasvovskaia S, Li J, Lin A, Hershenson M. Ras and mitogen-activated protein kinase kinase kinase-1 coregulate activator protein-1- and nuclear factor-kappaB-mediated gene expression in airway epithelial cells. Am J Respir Cell Mol Biol. 2003;28:762-9 pubmed
    ..TNF-alpha treatment induced both Ras and MEKK1 activation...
  42. Takekawa M, Tatebayashi K, Saito H. Conserved docking site is essential for activation of mammalian MAP kinase kinases by specific MAP kinase kinase kinases. Mol Cell. 2005;18:295-306 pubmed
    ..bind to their specific upstream MAP kinase kinase kinases (MAPKKKs), including MTK1 (MEKK4), ASK1, TAK1, TAO2, MEKK1, and Raf-1...
  43. McGrath M, Lee I, Buring J, Hunter D, De Vivo I. Novel breast cancer risk alleles and endometrial cancer risk. Int J Cancer. 2008;123:2961-4 pubmed publisher
    ..The molecular mechanisms underlying these differences remain to be defined. ..
  44. Dominguez Valentin M, Nakken S, Tubeuf H, Vodák D, Ekstrøm P, Nissen A, et al. Potentially pathogenic germline CHEK2 c.319+2T>A among multiple early-onset cancer families. Fam Cancer. 2018;17:141-153 pubmed publisher
  45. Zhu P, Baek S, Bourk E, Ohgi K, Garcia Bassets I, Sanjo H, et al. Macrophage/cancer cell interactions mediate hormone resistance by a nuclear receptor derepression pathway. Cell. 2006;124:615-29 pubmed
    ..TAB2 acts as a sensor for inflammatory signals by serving as a molecular beacon for recruitment of MEKK1, which in turn mediates dismissal of the N-CoR/HDAC complex and permits derepression of androgen and estrogen ..
  46. Huang D, Li X, Sun L, Huang P, Ying H, Wang H, et al. Regulation of Hippo signalling by p38 signalling. J Mol Cell Biol. 2016;8:328-37 pubmed publisher
    ..In Drosophila, overexpression of MAPKK gene licorne (lic), or MAPKKK gene Mekk1, promotes Yki activity and induces Hippo target gene expression...
  47. Cheng Y, Lin C, Chen J, Li C, Liu Y, Chen B. Induction of Connective Tissue Growth Factor Expression by Hypoxia in Human Lung Fibroblasts via the MEKK1/MEK1/ERK1/GLI-1/GLI-2 and AP-1 Pathways. PLoS ONE. 2016;11:e0160593 pubmed publisher
    ..We investigated the participation of mitogen-activated protein kinase kinase (MEK) kinase 1 (MEKK1)/MEK1/ERK1/GLI-1/2 and activator protein-1 (AP-1) signaling in hypoxia-induced CTGF expression in human lung ..
  48. Zhou Q, Dai J, Chen T, Dada L, Zhang X, Zhang W, et al. Downregulation of PKCζ/Pard3/Pard6b is responsible for lung adenocarcinoma cell EMT and invasion. Cell Signal. 2017;38:49-59 pubmed publisher
    ..Suppression of Pard3 increased chemoresistance in lung cancer cells. Together, these results suggest that reduced expression of PKCζ/Pard3/Pard6 contributes to NSCLC EMT, invasion, and chemoresistance. ..
  49. Jara L, Morales S, de Mayo T, Gonzalez Hormazabal P, Carrasco V, Godoy R. Mutations in BRCA1, BRCA2 and other breast and ovarian cancer susceptibility genes in Central and South American populations. Biol Res. 2017;50:35 pubmed publisher
    ..Pathogenic mutations or variants that increase BC risk have been reported in the following genes or genomic regions: ATM, BARD1, CHECK2, FGFR2, GSTM1, MAP3K1, MTHFR, PALB2, RAD51, TOX3, TP53, XRCC1, and 2q35. ..
  50. Oh S, Mouradian M. Regulation of Signal Transduction by DJ-1. Adv Exp Med Biol. 2017;1037:97-131 pubmed publisher
    ..kinase 1 (ASK1) activation as well as by inhibiting mitogen-activated protein kinase kinase kinase 1 (MEKK1/MAP3K1) activation of downstream apoptotic cascades...
  51. Nemoto S, DiDonato J, Lin A. Coordinate regulation of IkappaB kinases by mitogen-activated protein kinase kinase kinase 1 and NF-kappaB-inducing kinase. Mol Cell Biol. 1998;18:7336-43 pubmed
    ..We identified mitogen-activated protein kinase kinase kinase 1 (MEKK1) as an immediate upstream kinase of the IKK complex...
  52. Takano T, Cybulsky A, Yang X, Aoudjit L. Complement C5b-9 induces cyclooxygenase-2 gene transcription in glomerular epithelial cells. Am J Physiol Renal Physiol. 2001;281:F841-50 pubmed
    ..a constitutively active mitogen-activated protein or extracellular signal-regulated kinase kinase kinase (MEKK)-1, a kinase upstream of JNK, increased COX-2 promoter activity...
  53. Al Sadi R, Guo S, Ye D, Rawat M, Ma T. TNF-α Modulation of Intestinal Tight Junction Permeability Is Mediated by NIK/IKK-α Axis Activation of the Canonical NF-κB Pathway. Am J Pathol. 2016;186:1151-65 pubmed publisher
    ..NIK mediated the TNF-α activation of inhibitory κB kinase (IKK)-α, and MEKK1 mediated the activation of IKK complex, including IKK-β...
  54. Nakamura Y, Yujiri T, Nawata R, Tagami K, Tanizawa Y. MEK kinase 1 is essential for Bcr-Abl-induced STAT3 and self-renewal activity in embryonic stem cells. Oncogene. 2005;24:7592-8 pubmed
    ..b>MEK kinase 1 (MEKK1) is a 196-kDa mitogen-activated protein kinase (MAPK) kinase kinase involved in Bcr-Abl signal ..
  55. Yeh D, Wu C, Chin Y, Lu C, Wang Y, Chen M. Mechanisms of human lymphotoxin beta receptor activation on upregulation of CCL5/RANTES production. Int Immunopharmacol. 2015;28:220-9 pubmed publisher
    ..In addition, dominant negative mutants of ASK1, TAK1, and MEKK1 inhibited LTβR-induced RANTES expression...
  56. Lee K, Kim B, You H, Lee W. Uracil-induced signaling pathways for DUOX-dependent gut immunity. Fly (Austin). 2015;9:115-20 pubmed publisher
    ..C-β (PLCβ)-dependent calcium mobilization, whereas DUOX gene expression is mainly controlled by the MEKK1-p38 mitogen-activated protein kinase pathway...
  57. Zhang Z, Liu Y, Huang H, Gao M, Wu D, Kong Q, et al. The NLR protein SUMM2 senses the disruption of an immune signaling MAP kinase cascade via CRCK3. EMBO Rep. 2017;18:292-302 pubmed publisher
    MAP kinase signaling is an integral part of plant immunity. Disruption of the MEKK1-MKK1/2-MPK4 kinase cascade results in constitutive immune responses mediated by the NLR protein SUMM2, but the molecular mechanism is so far poorly ..
  58. Lee F, Hagler J, Chen Z, Maniatis T. Activation of the IkappaB alpha kinase complex by MEKK1, a kinase of the JNK pathway. Cell. 1997;88:213-22 pubmed
    ..A central kinase in the c-Jun activation pathway is mitogen-activated protein kinase/ERK kinase kinase-1 (MEKK1)...
  59. Luo W, Ng W, Jin L, Ye Z, Han J, Lin S. Axin utilizes distinct regions for competitive MEKK1 and MEKK4 binding and JNK activation. J Biol Chem. 2003;278:37451-8 pubmed
    ..It also activates the JNK mitogen-activated protein kinase by binding to MEKK1. However, it is intriguing that Axin requires several additional elements for JNK activation, including a ..
  60. Kurada B, Li L, Mulherkar N, Subramanian M, Prasad K, Prabhakar B. MADD, a splice variant of IG20, is indispensable for MAPK activation and protection against apoptosis upon tumor necrosis factor-alpha treatment. J Biol Chem. 2009;284:13533-41 pubmed publisher
    ..Loss of MADD expression resulted in reduced Grb2 and Sos1/2 recruitment to the TNFR1 complex and decreased Ras and MEKK1/2 activation...
  61. Yan M, Dai T, Deak J, Kyriakis J, Zon L, Woodgett J, et al. Activation of stress-activated protein kinase by MEKK1 phosphorylation of its activator SEK1. Nature. 1994;372:798-800 pubmed
    A kinase distinct from the MEK activator Raf, termed MEK kinase-1 (MEKK), was originally identified by virtue of its homology to kinases involved in yeast mating signal cascades. Like Raf, MEKK is capable of activating MEK in vitro...
  62. Saltzman A, Searfoss G, Marcireau C, Stone M, Ressner R, Munro R, et al. hUBC9 associates with MEKK1 and type I TNF-alpha receptor and stimulates NFkappaB activity. FEBS Lett. 1998;425:431-5 pubmed
    ..conjugating enzyme, was identified by yeast two-hybrid screening and coprecipitation studies to interact with MEKK1 and the type I TNF-alpha receptor, respectively...
  63. Hirano T, Shino Y, Saito T, Komoda F, Okutomi Y, Takeda A, et al. Dominant negative MEKK1 inhibits survival of pancreatic cancer cells. Oncogene. 2002;21:5923-8 pubmed
    ..in pancreatic cancer cells little is known about the activation of the downstream pathways of Ras, MEK-ERK and MEKK1-JNK, and their roles in cell survival and proliferation...
  64. Kim J, Lee J, Kim M, Cho E, Cho S, Choi E. Glycogen synthase kinase 3 beta is a natural activator of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 1 (MEKK1). J Biol Chem. 2003;278:13995-4001 pubmed
    ..GSK3 beta has now been shown to induce activation of the mitogen-activated protein kinase kinase kinase MEKK1 and thereby to promote signaling by the stress-activated protein kinase pathway...
  65. Morita K, Masamoto Y, Kataoka K, Koya J, Kagoya Y, Yashiroda H, et al. BAALC potentiates oncogenic ERK pathway through interactions with MEKK1 and KLF4. Leukemia. 2015;29:2248-56 pubmed publisher
    ..extracellular signal-regulated kinase (ERK) activity through an interaction with a scaffold protein MEK kinase-1 (MEKK1), which inhibits the interaction between ERK and MAP kinase phosphatase 3 (MKP3/DUSP6)...
  66. Yuan G, Li H, Yang W. The integration of Gβ and MAPK signaling cascade in zygote development. Sci Rep. 2017;7:8732 pubmed publisher
    ..protein AGB1 interacts with MPK3 and 6, MKK4 and 5, as well as the regulatory domains of YODA (YDA), the upstream MEKK of MKK4/5...
  67. Lee F, Peters R, Dang L, Maniatis T. MEKK1 activates both IkappaB kinase alpha and IkappaB kinase beta. Proc Natl Acad Sci U S A. 1998;95:9319-24 pubmed
    ..We have previously shown that mitogen-activated protein kinase/ERK kinase kinase 1 (MEKK1) can induce both this site-specific phosphorylation of IkappaB alpha at Ser-32 and Ser-36 in vivo and the activity ..
  68. Yoshida R, Takaesu G, Yoshida H, Okamoto F, Yoshioka T, Choi Y, et al. TRAF6 and MEKK1 play a pivotal role in the RIG-I-like helicase antiviral pathway. J Biol Chem. 2008;283:36211-20 pubmed publisher
    ..Instead, another MAP3K, MEKK1, was important for the activation of the IFN-beta promoter in response to poly(I:C)...
  69. Woolcott C, Maskarinec G, Haiman C, Verheus M, Pagano I, Le Marchand L, et al. Association between breast cancer susceptibility loci and mammographic density: the Multiethnic Cohort. Breast Cancer Res. 2009;11:R10 pubmed publisher
    ..Some effects may have been too small to be detected. The association with rs12443621 may provide clues as to how variation in TOX3 influences breast cancer risk. ..
  70. Wei X, Zhang E, Wang C, Gu D, Shen L, Wang M, et al. A MAP3k1 SNP predicts survival of gastric cancer in a Chinese population. PLoS ONE. 2014;9:e96083 pubmed publisher
    ..This raises the possibility for rs889312 polymorphisms to be used as an independent indicator for predicting the prognosis of diffuse-type gastric cancer within the Chinese population. ..
  71. Pomerance M, Multon M, Parker F, Venot C, Blondeau J, Tocque B, et al. Grb2 interaction with MEK-kinase 1 is involved in regulation of Jun-kinase activities in response to epidermal growth factor. J Biol Chem. 1998;273:24301-4 pubmed
    ..a specific interaction between the COOH-terminal SH3 domain of Grb2 and the NH2-terminal regulatory domain of MEKK1 in ER22 cells overexpressing the EGF receptor...
  72. Karandikar M, Xu S, Cobb M. MEKK1 binds raf-1 and the ERK2 cascade components. J Biol Chem. 2000;275:40120-7 pubmed
    ..b>MEKK1 is implicated in activation of the c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) and ERK1/2 ..
  73. Xu Y, Chen M, Liu C, Zhang X, Li W, Cheng H, et al. Association Study Confirmed Three Breast Cancer-Specific Molecular Subtype-Associated Susceptibility Loci in Chinese Han Women. Oncologist. 2017;22:890-894 pubmed publisher
  74. Martino B, Mammì C, Labate C, Rodi S, Ielo D, Priolo M, et al. Genetic risk of prediabetes and diabetes development in chronic myeloid leukemia patients treated with nilotinib. Exp Hematol. 2017;55:71-75 pubmed publisher
    ..In clinical practice, uGRS could help tailor the best tyrosine kinase inhibitor therapy. ..
  75. Xia Y, Wu Z, Su B, Murray B, Karin M. JNKK1 organizes a MAP kinase module through specific and sequential interactions with upstream and downstream components mediated by its amino-terminal extension. Genes Dev. 1998;12:3369-81 pubmed
    ..The specificity of JNK activation is determined by the MAPKK JNKK1, which interacts with the MAPKKK MEKK1 and JNK through its amino-terminal extension...
  76. Rui H, Fan E, Zhou H, Xu Z, Zhang Y, Lin S. SUMO-1 modification of the C-terminal KVEKVD of Axin is required for JNK activation but has no effect on Wnt signaling. J Biol Chem. 2002;277:42981-6 pubmed
    ..AxinDeltaC6 also failed to activate JNK, although it was intact in both its interaction with MEKK1 and homodimerization...
  77. Wu Y, Fan Y, Xue B, Luo L, Shen J, Zhang S, et al. Human glutathione S-transferase P1-1 interacts with TRAF2 and regulates TRAF2-ASK1 signals. Oncogene. 2006;25:5787-800 pubmed
  78. Miyata Y, Shibata T, Aoshima M, Tsubata T, Nishida E. The molecular chaperone TRiC/CCT binds to the Trp-Asp 40 (WD40) repeat protein WDR68 and promotes its folding, protein kinase DYRK1A binding, and nuclear accumulation. J Biol Chem. 2014;289:33320-32 pubmed publisher
    ..including dual specificity tyrosine phosphorylation-regulated protein kinase (DYRK1A), MAPK/ERK kinase kinase 1 (MEKK1), and Cullin4-damage-specific DNA-binding protein 1 (CUL4-DDB1)...
  79. Puzone R, Pfeffer U. SNP variants at the MAP3K1/SETD9 locus 5q11.2 associate with somatic PIK3CA variants in breast cancers. Eur J Hum Genet. 2017;25:384-387 pubmed publisher
  80. Baud V, Liu Z, Bennett B, Suzuki N, Xia Y, Karin M. Signaling by proinflammatory cytokines: oligomerization of TRAF2 and TRAF6 is sufficient for JNK and IKK activation and target gene induction via an amino-terminal effector domain. Genes Dev. 1999;13:1297-308 pubmed
    ..Oligomerization of the TRAF2 effector domain results in specific binding to MEKK1, a protein kinase capable of JNK, p38, and IKK activation, and induction of TNF-alpha and IL-1 responsive genes...
  81. Ritterhoff S, Farah C, Grabitzki J, Lochnit G, Skurat A, Schmitz M. The WD40-repeat protein Han11 functions as a scaffold protein to control HIPK2 and MEKK1 kinase functions. EMBO J. 2010;29:3750-61 pubmed publisher
    ..of Han11 to HIPK2, but also to the kinases DYRK1a, DYRK1b and mitogen-activated protein kinase kinase kinase 1 (MEKK1). Han11 was required to allow coupling of MEKK1 to DYRK1 and HIPK2...
  82. Deng M, Chen W, Takatori A, Peng Z, Zhang L, Mongan M, et al. A role for the mitogen-activated protein kinase kinase kinase 1 in epithelial wound healing. Mol Biol Cell. 2006;17:3446-55 pubmed
    The mitogen-activated protein kinase kinase (MEK) kinase 1 (MEKK1) mediates activin B signals required for eyelid epithelium morphogenesis during mouse fetal development...
  83. Su F, Li H, Yan C, Jia B, Zhang Y, Chen X. Depleting MEKK1 expression inhibits the ability of invasion and migration of human pancreatic cancer cells. J Cancer Res Clin Oncol. 2009;135:1655-63 pubmed publisher
    Mitogen-activated protein/ERK kinase 1 (MEKK1) is a Ser/Thr protein kinase belonging to the MEKK/STE11 subgroup of the MAPKKK family and plays a key role in tumor metastasis...
  84. Cramer T, Jüttner S, Plath T, Mergler S, Seufferlein T, Wang T, et al. Gastrin transactivates the chromogranin A gene through MEK-1/ERK- and PKC-dependent phosphorylation of Sp1 and CREB. Cell Signal. 2008;20:60-72 pubmed
  85. Sun B, Kim J, Nguyen H, Oh S, Kim S, Choi S, et al. MEKK1/MEKK4 are responsible for TRAIL-induced JNK/p38 phosphorylation. Oncol Rep. 2011;25:537-44 pubmed publisher
    ..The mitogen-activated protein kinase kinase 1 (MEKK1) and the apoptosis signal-regulating kinase 1 (ASK1) are considered to be possible candidates for the action of ..
  86. Liu C, Monda K, Taylor K, Lange L, Demerath E, Palmas W, et al. Genome-wide association of body fat distribution in African ancestry populations suggests new loci. PLoS Genet. 2013;9:e1003681 pubmed publisher
    ..These findings reinforce the concept that there are fat distribution loci that are independent of generalized adiposity. ..
  87. Sun B, Harrowe G, Reinhard C, Yoshihara C, Chu K, Zhuo S. Modulation of human cytomegalovirus immediate-early gene enhancer by mitogen-activated protein kinase kinase kinase-1. J Cell Biochem. 2001;83:563-73 pubmed
    ..Earlier reports by others have shown mitogen-activated protein kinase kinase kinase-1 (MEKK1) to be able to up-regulate HCMV-IE promoter through downstream mitogen-activated protein kinase (MAPK) pathways...
  88. Tricker E, ARVAND A, Kwan R, Chen G, Gallagher E, Cheng G. Apoptosis induced by cytoskeletal disruption requires distinct domains of MEKK1. PLoS ONE. 2011;6:e17310 pubmed publisher
    b>MEKK1 is a mitogen-activated protein kinase kinase kinase (MAP3K) that activates the MAPK JNK and is required for microtubule inhibitor-induced apoptosis in B cells...
  89. Ramnath R, Sun J, Adhikari S, Zhi L, Bhatia M. Role of PKC-delta on substance P-induced chemokine synthesis in pancreatic acinar cells. Am J Physiol Cell Physiol. 2008;294:C683-92 pubmed
    ..that SP stimulated an early phosphorylation of PKC isoform PKC-delta followed by increased activation of MAPKKK MEKK1 and MAPK ERK and JNK as well as transcription factor NF-kappaB and activator protein-1 driven chemokine production...
  90. Wierenga A, Vogelzang I, Eggen B, Vellenga E. Erythropoietin-induced serine 727 phosphorylation of STAT3 in erythroid cells is mediated by a MEK-, ERK-, and MSK1-dependent pathway. Exp Hematol. 2003;31:398-405 pubmed
    ..The EPO-induced STAT3 serine 727 phosphorylation is mediated by a pathway involving MEK, ERK, and MSK1. Furthermore, serine phosphorylation of STAT3 augments the transactivational potential of STAT3. ..
  91. Yu F, Harada J, Brown H, Deng H, Song M, Wu T, et al. Systematic identification of cellular signals reactivating Kaposi sarcoma-associated herpesvirus. PLoS Pathog. 2007;3:e44 pubmed
  92. Siu Y, Ching Y, Jin D. Activation of TORC1 transcriptional coactivator through MEKK1-induced phosphorylation. Mol Biol Cell. 2008;19:4750-61 pubmed publisher
    ..In this study, we report on the activation of TORC1 through MEKK1-mediated phosphorylation...