Map2k1

Summary

Gene Symbol: Map2k1
Description: mitogen-activated protein kinase kinase 1
Alias: MAPKK1, MEKK1, Mek1, Prkmk1, dual specificity mitogen-activated protein kinase kinase 1, ERK activator kinase 1, MAP kinase kinase 1, MAPK/ERK kinase 1, MAPKK 1, MEK 1, protein kinase, mitogen activated, kinase 1, p45
Species: mouse
Products:     Map2k1

Top Publications

  1. Scholl F, Dumesic P, Barragan D, Harada K, Charron J, Khavari P. Selective role for Mek1 but not Mek2 in the induction of epidermal neoplasia. Cancer Res. 2009;69:3772-8 pubmed publisher
    ..Mutations in this pathway have been associated with carcinogenesis and developmental disorders, making Mek1 and Mek2 prime therapeutic targets...
  2. Giroux S, Tremblay M, Bernard D, Cardin Girard J, Aubry S, Larouche L, et al. Embryonic death of Mek1-deficient mice reveals a role for this kinase in angiogenesis in the labyrinthine region of the placenta. Curr Biol. 1999;9:369-72 pubmed
    ..that although a single mek gene is present in Caenorhabditis elegans, Drosophila and Xenopus, two mek homologs, Mek1 and Mek2, are present in the mammalian cascade...
  3. Waskiewicz A, Flynn A, Proud C, Cooper J. Mitogen-activated protein kinases activate the serine/threonine kinases Mnk1 and Mnk2. EMBO J. 1997;16:1909-20 pubmed
    ..Mitogen- and stress-mediated MNK1 activation is blocked by inhibitors of MAP kinase kinase 1 (Mkk1) and p38, demonstrating that Mnk1 is downstream of multiple MAP kinases...
  4. Nadeau V, Guillemette S, Bélanger L, Jacob O, Roy S, Charron J. Map2k1 and Map2k2 genes contribute to the normal development of syncytiotrophoblasts during placentation. Development. 2009;136:1363-74 pubmed publisher
    The mammalian genome contains two ERK/MAP kinase kinase genes, Map2k1 and Map2k2, which encode dual-specificity kinases responsible for ERK/MAP kinase activation...
  5. Marks J, Gong Y, Chitale D, Golas B, McLellan M, Kasai Y, et al. Novel MEK1 mutation identified by mutational analysis of epidermal growth factor receptor signaling pathway genes in lung adenocarcinoma. Cancer Res. 2008;68:5524-8 pubmed publisher
    ..e., mitogen-activated protein kinase kinase 1 or MAP2K1) that substitutes asparagine for lysine at amino acid 57 (K57N) in the nonkinase portion of the kinase...
  6. Bueno O, De Windt L, Tymitz K, Witt S, Kimball T, Klevitsky R, et al. The MEK1-ERK1/2 signaling pathway promotes compensated cardiac hypertrophy in transgenic mice. EMBO J. 2000;19:6341-50 pubmed
    ..Here we generated nine transgenic mouse lines with cardiac-restricted expression of an activated MEK1 cDNA in the heart...
  7. Ishibe S, Joly D, Zhu X, Cantley L. Phosphorylation-dependent paxillin-ERK association mediates hepatocyte growth factor-stimulated epithelial morphogenesis. Mol Cell. 2003;12:1275-85 pubmed
    ..These experiments reveal that paxillin-dependent ERK activation at sites of cell-matrix interaction is critical for HGF-stimulated epithelial morphogenesis. ..
  8. Prusty D, Park B, Davis K, Farmer S. Activation of MEK/ERK signaling promotes adipogenesis by enhancing peroxisome proliferator-activated receptor gamma (PPARgamma ) and C/EBPalpha gene expression during the differentiation of 3T3-L1 preadipocytes. J Biol Chem. 2002;277:46226-32 pubmed
    ..MIX), dexamethasone (DEX), and fetal bovine serum induces a rapid but transient activation of MEK1 as indicated by extensive phosphorylation of ERK1 and ERK2 during the initial 2 h of adipogenesis...
  9. Bissonauth V, Roy S, Gravel M, Guillemette S, Charron J. Requirement for Map2k1 (Mek1) in extra-embryonic ectoderm during placentogenesis. Development. 2006;133:3429-40 pubmed
    b>Map2k1(-/-) embryos die at mid-gestation from abnormal development and hypovascularization of the placenta. We now show that this phenotype is associated with a decreased labyrinth cell proliferation and an augmented cell apoptosis...

More Information

Publications97

  1. Zhong J, Li X, McNamee C, Chen A, Baccarini M, Snider W. Raf kinase signaling functions in sensory neuron differentiation and axon growth in vivo. Nat Neurosci. 2007;10:598-607 pubmed
    ..We conclude that Raf function is crucial for several aspects of DRG neuron development, including differentiation and axon growth. ..
  2. Scholl F, Dumesic P, Barragan D, Harada K, Bissonauth V, Charron J, et al. Mek1/2 MAPK kinases are essential for Mammalian development, homeostasis, and Raf-induced hyperplasia. Dev Cell. 2007;12:615-29 pubmed
    ..knockout at a single level of this signaling pathway in mammals, and to investigate functional redundancy between Mek1 and Mek2, we disrupted these genes in murine and human epidermis...
  3. Catalanotti F, Reyes G, Jesenberger V, Galabova Kovacs G, de Matos Simoes R, Carugo O, et al. A Mek1-Mek2 heterodimer determines the strength and duration of the Erk signal. Nat Struct Mol Biol. 2009;16:294-303 pubmed publisher
    Mek1 and Mek2 (also known as Map2k1 and Map2k2, respectively) are evolutionarily conserved, dual-specificity kinases that mediate Erk1 and Erk2 activation during adhesion and growth factor signaling...
  4. Bélanger L, Roy S, Tremblay M, Brott B, Steff A, Mourad W, et al. Mek2 is dispensable for mouse growth and development. Mol Cell Biol. 2003;23:4778-87 pubmed
    ..Mek gene is present in Caenorhabditis elegans, Drosophila melanogaster, and Xenopus laevis, two Mek homologs, Mek1 and Mek2, are present in the mammalian cascade...
  5. Zheng C, Guan K. Cloning and characterization of two distinct human extracellular signal-regulated kinase activator kinases, MEK1 and MEK2. J Biol Chem. 1993;268:11435-9 pubmed
    ..MEK (MAP kinase or ERK kinase) is the immediate upstream activator kinase of ERK. Two cDNAs, MEK1 and MEK2, were cloned and sequenced. MEK1 and MEK2 encode 393 and 400 amino acid residues, respectively...
  6. Boucherat O, Landry Truchon K, Aoidi R, Houde N, Nadeau V, Charron J, et al. Lung development requires an active ERK/MAPK pathway in the lung mesenchyme. Dev Dyn. 2017;246:72-82 pubmed publisher
    ..Lung development necessitates a functional ERK/MAPK pathway in the lung mesenchymal layer in order to coordinate efficient epithelial-mesenchymal interactions. Developmental Dynamics 246:72-82, 2017. © 2016 Wiley Periodicals, Inc. ..
  7. Li X, Newbern J, Wu Y, Morgan Smith M, Zhong J, Charron J, et al. MEK Is a Key Regulator of Gliogenesis in the Developing Brain. Neuron. 2012;75:1035-50 pubmed publisher
    ..Radial progenitors deficient in both Mek1 and Mek2 fail to transition to the gliogenic mode in late embryogenesis, and astrocyte and oligodendroglial ..
  8. Huang Y, Li R, Chen X, Zhuo Y, Jin R, Qian X, et al. Doxycycline up-regulates the expression of IL-6 and GM-CSF via MAPK/ERK and NF-?B pathways in mouse thymic epithelial cells. Int Immunopharmacol. 2011;11:1143-9 pubmed publisher
    ..of IL-6 and GM-CSF was largely abolished after pretreatment of MTEC1 with either NF-?B inhibitor BAY11-7082 or MEK1/2 inhibitor U0126, supporting the involvement of the two pathways in the process...
  9. Laurent M, Ramirez D, Alberola Ila J. Kinase suppressor of Ras couples Ras to the ERK cascade during T cell development. J Immunol. 2004;173:986-92 pubmed
    ..This functional effect correlates with the ability of KSR to uncouple Ras from the ERK cascade when overexpressed. ..
  10. Aoki M, Yamashita T, Tohyama M. EphA receptors direct the differentiation of mammalian neural precursor cells through a mitogen-activated protein kinase-dependent pathway. J Biol Chem. 2004;279:32643-50 pubmed
    ..Our results identify EphA receptors as positive regulators of the mitogen-activated protein kinase pathway that exerts neurogenesis of neural precursor cells from the developing central nervous system. ..
  11. Kim M, Park J, Choi E, Park H. Presenilin acts as a positive regulator of basal level activity of ERK through the Raf-MEK1 signaling pathway. Biochem Biophys Res Commun. 2005;332:609-13 pubmed
    ..Furthermore, Elk-1 transcription activity also down-regulates in PS1(-/-) MEF cells. Collectively, our data suggest that PS can modulate the basal level of ERK activity through the Raf-MEK-dependent pathway. ..
  12. Silva P, Soares J, Brasil B, Nogueira S, Andrade A, de Magalhães J, et al. Differential role played by the MEK/ERK/EGR-1 pathway in orthopoxviruses vaccinia and cowpox biology. Biochem J. 2006;398:83-95 pubmed
  13. Ching S, Cunha G, Baskin L, Basson M, Klein O. Coordinated activity of Spry1 and Spry2 is required for normal development of the external genitalia. Dev Biol. 2014;386:1-11 pubmed publisher
  14. Xing L, Larsen R, Bjorklund G, Li X, Wu Y, Philpot B, et al. Layer specific and general requirements for ERK/MAPK signaling in the developing neocortex. elife. 2016;5: pubmed publisher
    ..Loss of Map2k1/2 (Mek1/2) led to deficits in corticospinal tract formation and subsequent corticospinal neuron apoptosis...
  15. Schulz L, Widmaier E, Qiu J, Roberts R. Effect of leptin on mouse trophoblast giant cells. Biol Reprod. 2009;80:415-24 pubmed publisher
    ..Leptin stimulated the phosphorylation of MEK (MAP2K1) but not signal transducer and activator of transcription 3 (STAT3) in the cultures, increased the concentration ..
  16. Nadeau V, Bissonauth V, Charron J. [Mek1 and Mek2 functions in the formation of the blood placental barrier]. Med Sci (Paris). 2012;28:409-15 pubmed publisher
    ..b>MEK1 and MEK2 are double specificity serine-threonine/tyrosine kinases responsible for the activation of ERK1 and ERK2...
  17. Emslie E, Jones T, Sheer D, Keyse S. The CL100 gene, which encodes a dual specificity (Tyr/Thr) MAP kinase phosphatase, is highly conserved and maps to human chromosome 5q34. Hum Genet. 1994;93:513-6 pubmed
    ..Fluorescence in situ hybridisation using a CL100 genomic probe confirms that the CL100 mRNA is transcribed from a single genetic locus and maps the gene to 5q34. ..
  18. Li A, Tian X, Zhang X, Huang S, Ma Y, Wu D, et al. Human polycystin-2 transgene dose-dependently rescues ADPKD phenotypes in Pkd2 mutant mice. Am J Pathol. 2015;185:2843-60 pubmed publisher
    ..The finding that the functional restoration of human PC2 significantly rescued ADPKD phenotypes in a dose-dependent manner suggests that increasing PC2 activity may be beneficial in some forms of ADPKD. ..
  19. Duesbery N, Webb C, Leppla S, Gordon V, Klimpel K, Copeland T, et al. Proteolytic inactivation of MAP-kinase-kinase by anthrax lethal factor. Science. 1998;280:734-7 pubmed
    ..shown that LF is a protease that cleaves the amino terminus of mitogen-activated protein kinase kinases 1 and 2 (MAPKK1 and MAPKK2) and that this cleavage inactivates MAPKK1 and inhibits the MAPK signal transduction pathway...
  20. Ihermann Hella A, Lume M, Miinalainen I, Pirttiniemi A, Gui Y, Peranen J, et al. Mitogen-activated protein kinase (MAPK) pathway regulates branching by remodeling epithelial cell adhesion. PLoS Genet. 2014;10:e1004193 pubmed publisher
    ..by genetically abrogating the pathway activity in mice lacking simultaneously dual-specificity protein kinases Mek1 and Mek2...
  21. Lange Carter C, Pleiman C, Gardner A, Blumer K, Johnson G. A divergence in the MAP kinase regulatory network defined by MEK kinase and Raf. Science. 1993;260:315-9 pubmed
    ..Thus, MEKK and Raf converge at MEK in the protein kinase network mediating the activation of MAPKs by hormones, growth factors, and neurotransmitters. ..
  22. Lu Z, Liu W, Huang H, He Y, Han Y, Rui Y, et al. Protein encoded by the Axin(Fu) allele effectively down-regulates Wnt signaling but exerts a dominant negative effect on c-Jun N-terminal kinase signaling. J Biol Chem. 2008;283:13132-9 pubmed publisher
  23. Nordström E, Luhr K, Ibanez C, Kristensson K. Inhibitors of the mitogen-activated protein kinase kinase 1/2 signaling pathway clear prion-infected cells from PrPSc. J Neurosci. 2005;25:8451-6 pubmed
    ..cells can be cleared from PrPSc by treatment with three inhibitors of mitogen-activated protein kinase kinase 1/2 (MEK1/2) [1,4-diamino-2,3-dicyano-1,4-bis(o-aminophenylmercapto)butadiene and 2-(2-amino-3-methyoxyphenyl)-4H-1-..
  24. Urosevic J, Sauzeau V, Soto Montenegro M, Reig S, Desco M, Wright E, et al. Constitutive activation of B-Raf in the mouse germ line provides a model for human cardio-facio-cutaneous syndrome. Proc Natl Acad Sci U S A. 2011;108:5015-20 pubmed publisher
    ..Clinically diagnosed CFC patients carry germ-line mutations in four different genes, B-RAF, MEK1, MEK2, and K-RAS...
  25. Piatelli M, Doughty C, Chiles T. Requirement for a hsp90 chaperone-dependent MEK1/2-ERK pathway for B cell antigen receptor-induced cyclin D2 expression in mature B lymphocytes. J Biol Chem. 2002;277:12144-50 pubmed
    ..Inhibition of the MEK1/2-ERK pathway was sufficient to abrogate BCR-induced cyclin D2 expression at the mRNA and protein levels...
  26. Labuda T, Christensen J, Rasmussen S, Bonnesen B, Karin M, Thomsen A, et al. MEK kinase 1 is a negative regulator of virus-specific CD8(+) T cells. Eur J Immunol. 2006;36:2076-84 pubmed
    MEK kinase 1 (MEKK1) is a potent JNK-activating kinase, a regulator of T helper cell differentiation, cytokine production and proliferation in vitro...
  27. Mandal M, Powers S, Ochiai K, Georgopoulos K, Kee B, Singh H, et al. Ras orchestrates exit from the cell cycle and light-chain recombination during early B cell development. Nat Immunol. 2009;10:1110-7 pubmed publisher
    ..Our data show how pre-BCR signaling poises pre-B cells to undergo differentiation after escape from IL-7R signaling. ..
  28. Wang S, Wei Q, Dong G, Dong Z. ERK-mediated suppression of cilia in cisplatin-induced tubular cell apoptosis and acute kidney injury. Biochim Biophys Acta. 2013;1832:1582-90 pubmed publisher
    ..U0126 up-regulated Polaris, but not Kif3a, in kidney tissues. It is suggested that ciliary regulation by ERK plays a role in cisplatin-induced tubular apoptosis and AKI. ..
  29. Lin C, Lin T, Lee M, Chen S, Chang J. Hyperglycemia: GDNF-EGR1 pathway target renal epithelial cell migration and apoptosis in diabetic renal embryopathy. PLoS ONE. 2013;8:e56731 pubmed publisher
    ..Our findings reveal a novel mechanism of GDNF/MAPK/EGR-1 activation playing a critical role in HRPTE cell migration, apoptosis and fetal hyperglycemic nephropathy. ..
  30. Zmajkovicova K, Jesenberger V, Catalanotti F, Baumgartner C, Reyes G, Baccarini M. MEK1 is required for PTEN membrane recruitment, AKT regulation, and the maintenance of peripheral tolerance. Mol Cell. 2013;50:43-55 pubmed publisher
    ..We now identify MEK1 as an essential regulator of lipid/protein phosphatase PTEN, through which it controls phosphatidylinositol-3-..
  31. Jo C, Cho S, Jo S. Mitogen-activated protein kinase kinase 1 (MEK1) stabilizes MyoD through direct phosphorylation at tyrosine 156 during myogenic differentiation. J Biol Chem. 2011;286:18903-13 pubmed publisher
    Previously, we reported that mitogen-activated protein kinase kinase 1 (MEK1) activated in the mid-stage of skeletal muscle differentiation promotes myogenic differentiation...
  32. Williamson D, Kimball S, Jefferson L. Acute treatment with TNF-alpha attenuates insulin-stimulated protein synthesis in cultures of C2C12 myotubes through a MEK1-sensitive mechanism. Am J Physiol Endocrinol Metab. 2005;289:E95-104 pubmed
    ..suggest that TNF abrogates insulin-induced stimulation of protein synthesis in myotubes through a decrease in eIF4F complex assembly independently of S6K1 and 4E-BP1 signaling and dependently on a MEK1-sensitive signaling pathway.
  33. Lee M, Kim J, Oh S, Jeong B, Hwang Y, Koh J. FGF2 Stimulates COUP-TFII Expression via the MEK1/2 Pathway to Inhibit Osteoblast Differentiation in C3H10T1/2 Cells. PLoS ONE. 2016;11:e0159234 pubmed publisher
    ..expression is regulated specifically by fibroblast growth factor 2 (FGF2), which mediates activation of the MEK1/2 pathway in mesenchymal lineage C3H10T1/2 cells...
  34. Meissner J, FREUND R, Krone D, Umeda P, Chang K, Gros G, et al. Extracellular signal-regulated kinase 1/2-mediated phosphorylation of p300 enhances myosin heavy chain I/beta gene expression via acetylation of nuclear factor of activated T cells c1. Nucleic Acids Res. 2011;39:5907-25 pubmed publisher
    ..In conclusion, ERK1/2-mediated phosphorylation of p300 is crucial for enhancing NFATc1 transactivation function by acetylation, which is essential for Ca(2+)-induced MyHCI/? expression. ..
  35. Choi Y, Gu Y, Oh J, Lee K. Osterix is regulated by Erk1/2 during osteoblast differentiation. Biochem Biophys Res Commun. 2011;415:472-8 pubmed publisher
    ..These results suggest that Erk1/2 regulates a major transcription factor, Osterix, during osteoblast differentiation by increasing its protein stability and transcriptional activity. ..
  36. Kamda J, Singer S. Phosphoinositide 3-kinase-dependent inhibition of dendritic cell interleukin-12 production by Giardia lamblia. Infect Immun. 2009;77:685-93 pubmed publisher
    ..These data suggest that this parasite actively interferes with host innate immunity, resulting in an immune response able to control the infection but devoid of strong inflammatory signals. ..
  37. van Wijk B, van den Berg G, Abu Issa R, Barnett P, van der Velden S, Schmidt M, et al. Epicardium and myocardium separate from a common precursor pool by crosstalk between bone morphogenetic protein- and fibroblast growth factor-signaling pathways. Circ Res. 2009;105:431-41 pubmed publisher
    ..exposed to recombinant FGF2 in vivo show enhanced epicardium formation, whereas a misbalance between FGF and BMP by Mek1/2 inhibition and BMP stimulation causes a developmental arrest of the epicardium and enhances myocardium formation ..
  38. Roberson M, Bliss S, Xie J, Navratil A, Farmerie T, Wolfe M, et al. Gonadotropin-releasing hormone induction of extracellular-signal regulated kinase is blocked by inhibition of calmodulin. Mol Endocrinol. 2005;19:2412-23 pubmed
    ..These data support the conclusion that Cam may have a critical role as a Ca2+ sensor in specifically linking Ca2+ flux with ERK activation within the GnRH signaling pathway. ..
  39. 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...
  40. Murakami S, Balmes G, McKinney S, Zhang Z, Givol D, de Crombrugghe B. Constitutive activation of MEK1 in chondrocytes causes Stat1-independent achondroplasia-like dwarfism and rescues the Fgfr3-deficient mouse phenotype. Genes Dev. 2004;18:290-305 pubmed
    We generated transgenic mice that express a constitutively active mutant of MEK1 in chondrocytes. These mice showed a dwarf phenotype similar to achondroplasia, the most common human dwarfism, caused by activating mutations in FGFR3...
  41. Cho K, Cai J, Kim H, Hosoya A, Ohshima H, Choi K, et al. ERK activation is involved in tooth development via FGF10 signaling. J Exp Zool B Mol Dev Evol. 2009;312:901-11 pubmed publisher
    ..The reported results will improve our understanding of the unique developmental processes of the dental epithelium and tooth growth, and will help to elucidate the fundamental mechanisms of ERK signaling underlying tooth development. ..
  42. Alessandrini A, Brott B, Erikson R. Differential expression of MEK1 and MEK2 during mouse development. Cell Growth Differ. 1997;8:505-11 pubmed
    Map/Erk kinase 1 (MEK1) and MEK2 activate the Erk/ MAP kinases and have been implicated in cell growth and differentiation...
  43. Vithayathil J, Pucilowska J, Goodnough L, ATIT R, Landreth G. Dentate Gyrus Development Requires ERK Activity to Maintain Progenitor Population and MAPK Pathway Feedback Regulation. J Neurosci. 2015;35:6836-48 pubmed publisher
    ..These findings establish that ERK signaling regulates maintenance of progenitor cells required for development of the dentate gyrus. ..
  44. Blasco R, Francoz S, Santamaria D, Canamero M, Dubus P, Charron J, et al. c-Raf, but not B-Raf, is essential for development of K-Ras oncogene-driven non-small cell lung carcinoma. Cancer Cell. 2011;19:652-63 pubmed publisher
    ..These results indicate that c-Raf plays a unique role in mediating K-Ras signaling and makes it a suitable target for therapeutic intervention. ..
  45. Dhillon A, Meikle S, Peyssonnaux C, Grindlay J, Kaiser C, Steen H, et al. A Raf-1 mutant that dissociates MEK/extracellular signal-regulated kinase activation from malignant transformation and differentiation but not proliferation. Mol Cell Biol. 2003;23:1983-93 pubmed
    ..The results further suggest that RafS259 mutants inhibit signaling pathways required to promote these biological processes. ..
  46. Nakajima A, Komazawa Sakon S, Takekawa M, Sasazuki T, Yeh W, Yagita H, et al. An antiapoptotic protein, c-FLIPL, directly binds to MKK7 and inhibits the JNK pathway. EMBO J. 2006;25:5549-59 pubmed
    ..Taken that ROS promote JNK activation and activation of the JNK pathway may promote ROS accumulation, c-FLIPL might block this positive feedback loop, thereby suppressing ROS accumulation. ..
  47. Choi J, Huebner A, Clement K, Walsh R, Savol A, Lin K, et al. Prolonged Mek1/2 suppression impairs the developmental potential of embryonic stem cells. Nature. 2017;548:219-223 pubmed publisher
    ..Mechanistically, we demonstrate that the inhibition of Mek1/2 is predominantly responsible for these effects, in part through the downregulation of DNA methyltransferases and ..
  48. Chen C, Lewis R, White M. IMP modulates KSR1-dependent multivalent complex formation to specify ERK1/2 pathway activation and response thresholds. J Biol Chem. 2008;283:12789-96 pubmed publisher
    ..MEK complexes that are required for c-Raf kinase activation and functional coupling of active kinases to downstream substrates. This property is engaged by IMP for modulation of signal amplitude. ..
  49. Brott B, Alessandrini A, Largaespada D, Copeland N, Jenkins N, Crews C, et al. MEK2 is a kinase related to MEK1 and is differentially expressed in murine tissues. Cell Growth Differ. 1993;4:921-9 pubmed
    b>MEK1 is a dual specificity kinase that phosphorylates and activates the Erk/MAP kinases Erk-1 and Erk-2 by phosphorylating them on threonine and tyrosine...
  50. Huang Z, Chen J, Regan J, Maguire C, Tang R, Dong X, et al. Loss of microRNAs in neural crest leads to cardiovascular syndromes resembling human congenital heart defects. Arterioscler Thromb Vasc Biol. 2010;30:2575-86 pubmed publisher
    ..Our results uncovered a central role for Dicer and miRNAs in NCC survival, migration, and patterning in craniofacial and cardiovascular development which, when mutated, lead to congenital neuro-craniofacial-cardiac defects. ..
  51. Xiong B, Yu L, Wang Q, Ai J, Yin S, Liu J, et al. Regulation of intracellular MEK1/2 translocation in mouse oocytes: cytoplasmic dynein/dynactin-mediated poleward transport and cyclin B degradation-dependent release from spindle poles. Cell Cycle. 2007;6:1521-7 pubmed
    We recently reported that MEK1/2 plays an important role in microtubule organization and spindle pole tethering in mouse oocytes, but how the intracellular transport of this protein is regulated remains unknown...
  52. Salmeron A, Ahmad T, Carlile G, Pappin D, Narsimhan R, Ley S. Activation of MEK-1 and SEK-1 by Tpl-2 proto-oncoprotein, a novel MAP kinase kinase kinase. EMBO J. 1996;15:817-26 pubmed
    ..Tpl-2, therefore, is a MAP kinase kinase kinase which can activate two MAP kinase pathways. After Raf and Mos, Tpl-2 is the third serine/threonine oncoprotein kinase that has been shown to function as a direct activator of MEK-1. ..
  53. Newbern J, Zhong J, Wickramasinghe R, Li X, Wu Y, Samuels I, et al. Mouse and human phenotypes indicate a critical conserved role for ERK2 signaling in neural crest development. Proc Natl Acad Sci U S A. 2008;105:17115-20 pubmed publisher
    ..Inactivation of upstream elements of the ERK cascade (B-Raf and C-Raf, MEK1 and MEK2) or a downstream effector, the transcription factor serum response factor resulted in analogous ..
  54. Dave S, Nanduri R, Dkhar H, Bhagyaraj E, Rao A, Gupta P. Nuclear MEK1 sequesters PPAR? and bisects MEK1/ERK signaling: a non-canonical pathway of retinoic acid inhibition of adipocyte differentiation. PLoS ONE. 2014;9:e100862 pubmed publisher
    ..the spatio-temporal regulation of the important signaling molecule mitogen-activated protein kinase kinase 1 (MEK1), likely by disrupting its export from the nucleus...
  55. Young A, Ngiow S, Madore J, Reinhardt J, Landsberg J, Chitsazan A, et al. Targeting Adenosine in BRAF-Mutant Melanoma Reduces Tumor Growth and Metastasis. Cancer Res. 2017;77:4684-4696 pubmed publisher
    ..Our results suggest that targeting adenosine may enhance therapeutic responses for melanoma patients receiving targeted or immune-based therapies. Cancer Res; 77(17); 4684-96. ©2017 AACR. ..
  56. McGary K, Park T, Woods J, Cha H, Wallingford J, Marcotte E. Systematic discovery of nonobvious human disease models through orthologous phenotypes. Proc Natl Acad Sci U S A. 2010;107:6544-9 pubmed publisher
    ..Phenologs reveal functionally coherent, evolutionarily conserved gene networks-many predating the plant-animal divergence-capable of identifying candidate disease genes. ..
  57. Riobo N, Haines G, Emerson C. Protein kinase C-delta and mitogen-activated protein/extracellular signal-regulated kinase-1 control GLI activation in hedgehog signaling. Cancer Res. 2006;66:839-45 pubmed
    ..Our results identify PKCdelta and MEK-1 as essential, positive regulators of GLI-mediated HH signaling. Furthermore, our findings suggest that tumors with deregulated HH and ERK synergize to stimulate cell proliferation pathways. ..
  58. el Azzouzi H, Leptidis S, Bourajjaj M, van Bilsen M, da Costa Martins P, De Windt L. MEK1 inhibits cardiac PPAR? activity by direct interaction and prevents its nuclear localization. PLoS ONE. 2012;7:e36799 pubmed publisher
    ..In response to increased workload, the mitogen-activated protein kinase kinase (MAPKK) MEK1 has been shown to be active...
  59. Jo C, Jang B, Jo S. MEK1 plays contrary stage-specific roles in skeletal myogenic differentiation. Cell Signal. 2009;21:1910-7 pubmed publisher
    ..this discrepancy may arise from the stage-specific, different roles of mitogen-activated protein kinase kinase 1 (MEK1)...
  60. Noël A, Poitras I, Julien J, Petry F, Morin F, Charron J, et al. ERK (MAPK) does not phosphorylate tau under physiological conditions in vivo or in vitro. Neurobiol Aging. 2015;36:901-2 pubmed publisher
    ..Finally, ERK1/2 was inhibited, but tau phosphorylation was not altered in Mek1-/- mice...
  61. Crews C, Alessandrini A, Erikson R. The primary structure of MEK, a protein kinase that phosphorylates the ERK gene product. Science. 1992;258:478-80 pubmed
    ..The structure of this protein kinase, denoted MEK1, for MAP kinase or ERK kinase, was elucidated from a complementary DNA sequence and shown to be a protein of 393 ..
  62. Tsioumpekou M, Papadopoulos N, Burovic F, Heldin C, Lennartsson J. Platelet-derived growth factor (PDGF)-induced activation of Erk5 MAP-kinase is dependent on Mekk2, Mek1/2, PKC and PI3-kinase, and affects BMP signaling. Cell Signal. 2016;28:1422-31 pubmed publisher
    ..MAP kinase is activated in response to PDGF-BB in the smooth muscle cell line MOVAS in a manner dependent on Mekk2, Mek1/2, Mek5, PI3-kinase and protein kinase C (PKC)...
  63. Chung E, Hsu C, Kondo M. Constitutive MAP kinase activation in hematopoietic stem cells induces a myeloproliferative disorder. PLoS ONE. 2011;6:e28350 pubmed publisher
    ..Our results clearly demonstrate the proto-oncogenic property of the MEK/ERK pathway in hematopoietic cells, which manifest in MDS/MPN development. ..
  64. Yao Z, Seger R. The ERK signaling cascade--views from different subcellular compartments. Biofactors. 2009;35:407-16 pubmed publisher
    ..In this review, we discuss the intracellular localizations of different components of the ERK cascade, and the impact of these localizations on their activation and specificity. ..
  65. Yeh C, Malhotra D, Yang Y, Xu Y, Fan Y, Li H, et al. MEK1-induced physiological hypertrophy inhibits chronic post-myocardial infarction remodeling in mice. J Cell Biochem. 2013;114:47-55 pubmed publisher
    ..stroke work, and end-systolic elastance were all preserved in transgenic mice with CM-specific upregulation of the MEK1-ERK1/2 signaling pathway (MEK1 Tg) compared to wildtype (WT) controls (5.8% decline vs. 17.3%, P < 0...
  66. Lee M, Koh W. Raf-independent and MEKK1-dependent activation of NF-kappaB by hydrogen peroxide in 70Z/3 pre-B lymphocyte tumor cells. J Cell Biochem. 2003;88:545-56 pubmed
    ..Instead, treatment of 70Z/3 cells with H(2)O(2) resulted in the activation of MAPK kinase kinase 1 (MEKK1) as well as JNK...
  67. Bluhm B, Ehlen H, Holzer T, Georgieva V, Heilig J, Pitzler L, et al. miR-322 stabilizes MEK1 expression to inhibit RAF/MEK/ERK pathway activation in cartilage. Development. 2017;144:3562-3577 pubmed publisher
    ..Among the various miR-322 target genes in the RAF/MEK/ERK pathway, only Mek1 was identified as a regulated target in chondrocytes...
  68. Goc A, Sabbineni H, Abdalla M, Somanath P. p70 S6-kinase mediates the cooperation between Akt1 and Mek1 pathways in fibroblast-mediated extracellular matrix remodeling. Biochim Biophys Acta. 2015;1853:1626-35 pubmed publisher
    Previous studies have demonstrated both synergistic and opposing effects of Akt and Mek1/2 in various cell functions and disease states...
  69. Yu W, Fantl W, Harrowe G, Williams L. Regulation of the MAP kinase pathway by mammalian Ksr through direct interaction with MEK and ERK. Curr Biol. 1998;8:56-64 pubmed
    ..Together with the data from genetic analyses, our findings lead us to propose that mKsr-1 may control MAP kinase signaling by serving as a scaffold protein that links MEK and its substrate ERK. ..
  70. Liu J, Puscheck E, Wang F, Trostinskaia A, Barisic D, Maniere G, et al. Serine-threonine kinases and transcription factors active in signal transduction are detected at high levels of phosphorylation during mitosis in preimplantation embryos and trophoblast stem cells. Reproduction. 2004;128:643-54 pubmed
    ..with the spindle complex during M phase, but one (p38MAPK) associated with the spindle pole and five (Cdx2, MEK1, 2, p27, and RSK1) associated with the DNA...
  71. Aoidi R, Maltais A, Charron J. Functional redundancy of the kinases MEK1 and MEK2: Rescue of the Mek1 mutant phenotype by Mek2 knock-in reveals a protein threshold effect. Sci Signal. 2016;9:ra9 pubmed publisher
    The mammalian genome contains two mitogen-activated protein kinase (MAPK) kinase (MEK)-encoding genes, Mek1 and Mek2. MEKs phosphorylate and activate the two extracellular signal-regulated kinase (ERK) isoforms ERK1 and ERK2...
  72. Holmström T, Mattsson C, Fälting J, Nedergaard J. Differential signalling pathways for EGF versus PDGF activation of Erk1/2 MAP kinase and cell proliferation in brown pre-adipocytes. Exp Cell Res. 2008;314:3581-92 pubmed publisher
  73. Ito M, Yoshioka K, Akechi M, Yamashita S, Takamatsu N, Sugiyama K, et al. JSAP1, a novel jun N-terminal protein kinase (JNK)-binding protein that functions as a Scaffold factor in the JNK signaling pathway. Mol Cell Biol. 1999;19:7539-48 pubmed
    ..In similar cotransfection studies, JSAP1 also interacted with SEK1 MAPKK and MEKK1 MAPKKK, which are involved in the JNK cascades...
  74. Matzkin M, Yamashita S, Ascoli M. The ERK1/2 pathway regulates testosterone synthesis by coordinately regulating the expression of steroidogenic genes in Leydig cells. Mol Cell Endocrinol. 2013;370:130-7 pubmed publisher
    Adult mice with a Leydig cell specific deletion of MAPK kinase (MEK) 1 and 2 (Mek1(f)(/)(f);Mek2(-/-);Cre(+)) mice display Leydig cell hypoplasia and hypergonadotropic hypogonadism...
  75. Arwert E, Lal R, Quist S, Rosewell I, Van Rooijen N, Watt F. Tumor formation initiated by nondividing epidermal cells via an inflammatory infiltrate. Proc Natl Acad Sci U S A. 2010;107:19903-8 pubmed publisher
    ..In transgenic mice, expression of activated MAPK kinase 1 (MEK1) in the suprabasal, nondividing, differentiated cell layers (InvEE transgenics) results in epidermal ..
  76. Zhang Y, Gao X, Chen S, Zhao M, Chen J, Liu R, et al. Cyclin-dependent kinase 5 contributes to endoplasmic reticulum stress induced podocyte apoptosis via promoting MEKK1 phosphorylation at Ser280 in diabetic nephropathy. Cell Signal. 2017;31:31-40 pubmed publisher
    ..On the other hand, Cdk5 phosphorylates MEKK1 at Ser280 in tunicamycin treated podocytes, and together, they increase the JNK phosphorylation...
  77. Kunnen S, Leonhard W, Semeins C, Hawinkels L, Poelma C, Ten Dijke P, et al. Fluid shear stress-induced TGF-?/ALK5 signaling in renal epithelial cells is modulated by MEK1/2. Cell Mol Life Sci. 2017;74:2283-2298 pubmed publisher
    ..To study potential involvement of MAPK/ERK signaling, cells were treated with a MEK1/2 inhibitor...
  78. Xiang X, Zang M, Waelde C, Wen R, Luo Z. Phosphorylation of 338SSYY341 regulates specific interaction between Raf-1 and MEK1. J Biol Chem. 2002;277:44996-5003 pubmed
    The present study characterizes the interaction between the Raf-1 kinase domain and MEK1 and examines whether the magnitude of their interaction correlates to the ability of Raf to phosphorylate MEK1...
  79. Quiel A, Jürgen B, Greinacher A, Lassen S, Wörl R, Witt S, et al. Sensitive detection of idiotypic platelet-reactive alloantibodies by an electrical protein chip. Biosens Bioelectron. 2012;36:207-11 pubmed publisher
    ..With this electrical chip assay it is possible to detect antibodies against HPA-1a, HPA-5b and HLA with high sensitivity and specificity in less than half the duration of the MAIPA protocol with similar intra- and interassay variance. ..
  80. Chandrakesan P, Ahmed I, Anwar T, Wang Y, Sarkar S, Singh P, et al. Novel changes in NF-{kappa}B activity during progression and regression phases of hyperplasia: role of MEK, ERK, and p38. J Biol Chem. 2010;285:33485-98 pubmed publisher
    ..Phosphorylation of MEK1/2 (Ser(217/221)), ERK1/2 (Thr(202)/Tyr(204)), and p38 (Thr(180)/Tyr(182)) paralleled IKK?/? kinetics at days 6 and ..
  81. Yoshida T, Iwamoto T, Adachi K, Yokota T, Miyake Y, Hamaguchi M. Functional analysis of the effect of forced activation of STAT3 on M1 mouse leukemia cells. Int J Mol Med. 2005;15:269-75 pubmed
    ..Introduction of a constitutive active MAP kinase kinase (MEK1) into M1/STAT3ER cells did not induce differentiation either...
  82. Bloom M, Murakami S, Cody D, Montufar Solis D, Duke P. Aspects of achondroplasia in the skulls of dwarf transgenic mice: a cephalometric study. Anat Rec A Discov Mol Cell Evol Biol. 2006;288:316-22 pubmed
    ..in chondrocyte differentiation, a transgenic mouse was generated that expresses a constitutively active mutant of MEK1 in chondrocytes and exhibits dwarfing characteristics typical of human achondroplasia, i.e...
  83. Sugawara T, Moriguchi T, Nishida E, Takahama Y. Differential roles of ERK and p38 MAP kinase pathways in positive and negative selection of T lymphocytes. Immunity. 1998;9:565-74 pubmed
    ..These results suggest that intracellular signals through different MAP kinase cascades selectively guide positive and negative selection of T lymphocytes. ..
  84. Meriane M, Duhamel S, Lejeune L, Galipeau J, Annabi B. Cooperation of matrix metalloproteinases with the RhoA/Rho kinase and mitogen-activated protein kinase kinase-1/extracellular signal-regulated kinase signaling pathways is required for the sphingosine-1-phosphate-induced mobilization of marrow-derive. Stem Cells. 2006;24:2557-65 pubmed
    ..S1P-induced activation of the mitogen-activated protein kinase kinase-1 (MEK1)/ERK pathway also contributed to the induction of the actin stress fibers and to the redistribution of paxillin at ..
  85. Pan C, Liou Y, Low B. Active Mek2 as a regulatory scaffold that promotes Pin1 binding to BPGAP1 to suppress BPGAP1-induced acute Erk activation and cell migration. J Cell Sci. 2010;123:903-16 pubmed publisher
    ..Thus, Pin1 regulates BPGAP1 function in Rho and Erk signalling, with active Mek2 serving as a novel regulatory scaffold that promotes crosstalk between RhoGAP, Pin1 and Erk in the regulation of cell migration. ..
  86. Shakespeare T, Sellitto C, Li L, Rubinos C, Gong X, Srinivas M, et al. Interaction between Connexin50 and mitogen-activated protein kinase signaling in lens homeostasis. Mol Biol Cell. 2009;20:2582-92 pubmed publisher
    ..These results indicate that MAPK signaling specifically modulates coupling mediated by Cx50 and that gap junctional communication and signal transduction pathways may interact in osmotic regulation during postnatal fiber development. ..
  87. Kamio N, Akifusa S, Yamaguchi N, Yamashita Y. Induction of granulocyte colony-stimulating factor by globular adiponectin via the MEK-ERK pathway. Mol Cell Endocrinol. 2008;292:20-5 pubmed publisher
    ..The gAd-induced secretion of G-CSF increased in a time- and dose-dependent manner. U0126 (MEK1/2 inhibitor) and PD98059 (MEK1 inhibitor) reduced the gAd-induced G-CSF mRNA expression and G-CSF protein ..
  88. Moniz L, Stambolic V. Nek10 mediates G2/M cell cycle arrest and MEK autoactivation in response to UV irradiation. Mol Cell Biol. 2011;31:30-42 pubmed publisher
    ..Nek10 physically associated with Raf-1 and MEK1 in a Raf-1-dependent manner, and the formation of this complex was necessary for Nek10-mediated MEK1 activation...