Gene Symbol: MEK1
Description: mitogen-activated protein kinase kinase 1
Alias: CFC3, MAPKK1, MEK1, MKK1, PRKMK1, dual specificity mitogen-activated protein kinase kinase 1, ERK activator kinase 1, MAPK/ERK kinase 1, MAPKK 1, MEK 1, protein kinase, mitogen-activated, kinase 1 (MAP kinase kinase 1)
Species: human

Top Publications

  1. pmc Preexisting MEK1 exon 3 mutations in V600E/KBRAF melanomas do not confer resistance to BRAF inhibitors
    Hubing Shi
    Division of Dermatology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California 90095 1750, USA
    Cancer Discov 2:414-24. 2012
  2. doi In vivo antitumor activity of MEK and phosphatidylinositol 3-kinase inhibitors in basal-like breast cancer models
    Klaus P Hoeflich
    Translational Oncology, Genentech, Inc, South San Francisco, California 94080, USA
    Clin Cancer Res 15:4649-64. 2009
  3. doi Safety, pharmacokinetic, pharmacodynamic, and efficacy data for the oral MEK inhibitor trametinib: a phase 1 dose-escalation trial
    Jeffrey R Infante
    Sarah Cannon Research Institute Tennessee Oncology, PLLC, Nashville, TN, USA
    Lancet Oncol 13:773-81. 2012
  4. pmc Novel MEK1 mutation identified by mutational analysis of epidermal growth factor receptor signaling pathway genes in lung adenocarcinoma
    Jenifer L Marks
    Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Cancer Res 68:5524-8. 2008
  5. ncbi Germline mutations in genes within the MAPK pathway cause cardio-facio-cutaneous syndrome
    Pablo Rodriguez-Viciana
    Comprehensive Cancer Center and Cancer Research Institute, University of California, San Francisco, CA 94115, USA
    Science 311:1287-90. 2006
  6. pmc Activation of MEK family kinases requires phosphorylation of two conserved Ser/Thr residues
    C F Zheng
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor 48109
    EMBO J 13:1123-31. 1994
  7. ncbi Molecular and clinical characterization of cardio-facio-cutaneous (CFC) syndrome: overlapping clinical manifestations with Costello syndrome
    Yoko Narumi
    Department of Medical Genetics, Tohoku University School of Medicine, Sendai, Japan
    Am J Med Genet A 143:799-807. 2007
  8. ncbi Inhibition of caspase-9 through phosphorylation at Thr 125 by ERK MAPK
    Lindsey A Allan
    Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, UK
    Nat Cell Biol 5:647-54. 2003
  9. ncbi The CXC chemokine stromal cell-derived factor activates a Gi-coupled phosphoinositide 3-kinase in T lymphocytes
    Y Sotsios
    Department of Pharmacy and Pharmacology, Bath University, Claverton Down, Bath, Avon, United Kingdom
    J Immunol 163:5954-63. 1999
  10. ncbi Blockade of the MAP kinase pathway suppresses growth of colon tumors in vivo
    J S Sebolt-Leopold
    Department of Cell Biology, Parke Davis Pharmaceutical Research, Division of Warner Lambert, Ann Arbor, Michigan 48105, USA
    Nat Med 5:810-6. 1999

Detail Information

Publications390 found, 100 shown here

  1. pmc Preexisting MEK1 exon 3 mutations in V600E/KBRAF melanomas do not confer resistance to BRAF inhibitors
    Hubing Shi
    Division of Dermatology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California 90095 1750, USA
    Cancer Discov 2:414-24. 2012
    ..Somatic activating MEK1 mutations are thought to be rare in melanomas, but their potential concurrence with V600E/KBRAF may be selected for ..
  2. doi In vivo antitumor activity of MEK and phosphatidylinositol 3-kinase inhibitors in basal-like breast cancer models
    Klaus P Hoeflich
    Translational Oncology, Genentech, Inc, South San Francisco, California 94080, USA
    Clin Cancer Res 15:4649-64. 2009
    ..We investigated the role of mitogen-activated protein kinase kinase (MEK) and phosphatidylinositol 3-kinase (PI3K) inhibitors as targeted therapies for basal-like breast cancer...
  3. doi Safety, pharmacokinetic, pharmacodynamic, and efficacy data for the oral MEK inhibitor trametinib: a phase 1 dose-escalation trial
    Jeffrey R Infante
    Sarah Cannon Research Institute Tennessee Oncology, PLLC, Nashville, TN, USA
    Lancet Oncol 13:773-81. 2012
    ..Trametinib is a selective, orally administered MEK1/MEK2 inhibitor...
  4. pmc Novel MEK1 mutation identified by mutational analysis of epidermal growth factor receptor signaling pathway genes in lung adenocarcinoma
    Jenifer L Marks
    Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Cancer Res 68:5524-8. 2008
    ..We have identified in 2 of 207 primary lung tumors a somatic activating mutation in exon 2 of MEK1 (i.e...
  5. ncbi Germline mutations in genes within the MAPK pathway cause cardio-facio-cutaneous syndrome
    Pablo Rodriguez-Viciana
    Comprehensive Cancer Center and Cancer Research Institute, University of California, San Francisco, CA 94115, USA
    Science 311:1287-90. 2006
    ..Furthermore, three of five individuals without BRAF mutations had missense mutations in either MEK1 or MEK2, downstream effectors of B-Raf...
  6. pmc Activation of MEK family kinases requires phosphorylation of two conserved Ser/Thr residues
    C F Zheng
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor 48109
    EMBO J 13:1123-31. 1994
    ..Here, we report the activation phosphorylation sites of human MEK1 and yeast STE7 kinase as determined by a combination of biochemical and genetic approaches...
  7. ncbi Molecular and clinical characterization of cardio-facio-cutaneous (CFC) syndrome: overlapping clinical manifestations with Costello syndrome
    Yoko Narumi
    Department of Medical Genetics, Tohoku University School of Medicine, Sendai, Japan
    Am J Med Genet A 143:799-807. 2007
    ..We analyzed KRAS, BRAF, and MAP2K1/2 (MEK1/2) in 13 new CFC patients and identified five BRAF and one MAP2K1 mutations in nine patients...
  8. ncbi Inhibition of caspase-9 through phosphorylation at Thr 125 by ERK MAPK
    Lindsey A Allan
    Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, UK
    Nat Cell Biol 5:647-54. 2003
    ..activity is overcome by treatment with the broad-specificity kinase inhibitor staurosporine or with inhibitors of MEK1/2...
  9. ncbi The CXC chemokine stromal cell-derived factor activates a Gi-coupled phosphoinositide 3-kinase in T lymphocytes
    Y Sotsios
    Department of Pharmacy and Pharmacology, Bath University, Claverton Down, Bath, Avon, United Kingdom
    J Immunol 163:5954-63. 1999
    ..Hence, it appears that ERK1/2 activation is dependent on PI 3-kinase activation, and both biochemical events are involved in the regulation of SDF-1-stimulated chemotaxis...
  10. ncbi Blockade of the MAP kinase pathway suppresses growth of colon tumors in vivo
    J S Sebolt-Leopold
    Department of Cell Biology, Parke Davis Pharmaceutical Research, Division of Warner Lambert, Ann Arbor, Michigan 48105, USA
    Nat Med 5:810-6. 1999
    ..These data indicate that MEK inhibitors represent a promising, noncytotoxic approach to the clinical management of colon cancer...
  11. pmc Phase I pharmacokinetic and pharmacodynamic study of the oral, small-molecule mitogen-activated protein kinase kinase 1/2 inhibitor AZD6244 (ARRY-142886) in patients with advanced cancers
    Alex A Adjei
    Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA
    J Clin Oncol 26:2139-46. 2008
    ..To assess the tolerability, pharmacokinetics (PKs), and pharmacodynamics (PDs) of the mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor AZD6244 (ARRY-142886) in patients with advanced cancer...
  12. ncbi Structures of human MAP kinase kinase 1 (MEK1) and MEK2 describe novel noncompetitive kinase inhibition
    Jeffrey F Ohren
    Department of Discovery Technologies, Pfizer Global Research and Development, 2800 Plymouth Road, Ann Arbor, Michigan 48105, USA
    Nat Struct Mol Biol 11:1192-7. 2004
    b>MEK1 and MEK2 are closely related, dual-specificity tyrosine/threonine protein kinases found in the Ras/Raf/MEK/ERK mitogen-activated protein kinase (MAPK) signaling pathway...
  13. ncbi Laminin-10/11 and fibronectin differentially prevent apoptosis induced by serum removal via phosphatidylinositol 3-kinase/Akt- and MEK1/ERK-dependent pathways
    Jianguo Gu
    Division of Protein Chemistry, Institute for Protein Research, Osaka University, 3 2 Yamadaoka, Suita, Osaka 565 0871, Japan
    J Biol Chem 277:19922-8. 2002 treatment with PD98059, a specific inhibitor of mitogen- or extracellular signal-regulated kinase kinase-1 (MEK1) and by expression of a dominant-negative mutant of MEK1...
  14. ncbi Critical role of the phosphatidylinositol 3-kinase/Akt/glycogen synthase kinase-3 signaling pathway in recovery from anthrax lethal toxin-induced cell cycle arrest and MEK cleavage in macrophages
    Soon Duck Ha
    Department of Microbiology and Immunology, Siebens Drake Research Institute, University of Western Ontario, London, Ontario, Canada N6G 2V4
    J Biol Chem 282:36230-9. 2007
    ..This study showed that a brief exposure of LeTx caused a continual MEK1 cleavage and prevented tumor necrosis factor-alpha (TNF) production in response to lipopolysaccharide (LPS) in non-..
  15. ncbi MP1: a MEK binding partner that enhances enzymatic activation of the MAP kinase cascade
    H J Schaeffer
    Department of Microbiology and Cancer Center, University of Virginia Health Sciences Center, Charlottesville, VA 22908, USA
    Science 281:1668-71. 1998
    ..A protein called MP1 (MEK Partner 1) was identified that bound specifically to MEK1 and ERK1 and facilitated their activation...
  16. ncbi MEK1-induced Golgi dynamics during cell cycle progression is partly mediated by Polo-like kinase-3
    Suqing Xie
    Department of Medicine, New York Medical College, Valhalla, NY 10595, USA
    Oncogene 23:3822-9. 2004
    b>MEK1, a gene product that regulates cell growth and differentiation, also plays an important role in Golgi breakdown during the cell cycle...
  17. ncbi Selective activation of MEK1 but not MEK2 by A-Raf from epidermal growth factor-stimulated Hela cells
    X Wu
    Department of Biological Chemistry and the Institute of Gerontology, The University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    J Biol Chem 271:3265-71. 1996
    ..were substituted by alanines, was used as a bait, whereas no positive clones were isolated when the wild type MEK1 was used as a bait in a similar screening...
  18. doi Activation of mitogen activated protein kinase-Erk kinase (MEK) increases T cell immunoglobulin mucin domain-3 (TIM-3) transcription in human T lymphocytes and a human mast cell line
    Soo Jin Yoon
    Department of Microbiology, Ajou University School of Medicine, Youngtongku Wonchondong San 5, Suwon 442 749, Republic of Korea
    Mol Immunol 48:1778-83. 2011
    ..5kb TIM-3 promoter activity was reduced by MEK inhibitors, but was not responsive to TGF-β stimulation in HMC-1 cells. These results suggest the regulatory role of MEK in TIM-3 transcription by human CD4+ T cells and mast cells...
  19. pmc Hepatitis C virus core protein interacts with 14-3-3 protein and activates the kinase Raf-1
    H Aoki
    Department of Experimental Pathology, Cancer Institute, Japanese Foundation for Cancer Research, 1 37 1 Kami Ikebukuro, Toshima ku, Tokyo 170 8455, Japan
    J Virol 74:1736-41. 2000
    ..These results suggest that HCV core protein may represent a novel type of Raf-1 kinase-activating protein through its interaction with 14-3-3 protein and may contribute to hepatocyte growth regulation...
  20. ncbi The roles of phosphatidylinositol 3-kinase and protein kinase Czeta for thrombopoietin-induced mitogen-activated protein kinase activation in primary murine megakaryocytes
    P Rojnuckarin
    Division of Hematology, University of Washington School of Medicine, Seattle, Washington 98195, USA
    J Biol Chem 276:41014-22. 2001
    ..These data demonstrate a novel role of PI3K and PKCzeta in steady-state megakaryopoiesis...
  21. pmc Identification of a novel mitogen-activated protein kinase kinase activation domain recognized by the inhibitor PD 184352
    Amy M Delaney
    Cell Biology, Discovery Technologies, Pfizer Global Research and Development, Ann Arbor Laboratories, Ann Arbor, Michigan 48105, USA
    Mol Cell Biol 22:7593-602. 2002
    ..a genetic screen in the yeast Saccharomyces cerevisiae, we identified a novel autoactivation region in mammalian MEK1 that is involved in binding the specific MEK inhibitor, PD 184352...
  22. ncbi Thermodynamics of nucleotide and non-ATP-competitive inhibitor binding to MEK1 by circular dichroism and isothermal titration calorimetry
    Catherine K Smith
    Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA
    Biochemistry 46:1358-67. 2007
    b>MEK1 is a member of the MAPK signal transduction pathway that responds to growth factors and cytokines...
  23. pmc Nuclear factor-kappa B activation by the CXC chemokine melanoma growth-stimulatory activity/growth-regulated protein involves the MEKK1/p38 mitogen-activated protein kinase pathway
    D Wang
    Department of Veterans Affairs, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    J Biol Chem 276:3650-9. 2001
    ..Moreover, MGSA/GROalpha induction of NF-kappaB is independent of the MEK1/ERK cascade, because MGSA/GROalpha failed to increase ERK and ELK activation, and specific chemical inhibitors for ..
  24. ncbi Constitutive activation of the Saccharomyces cerevisiae mating response pathway by a MAP kinase kinase from Candida albicans
    K L Clark
    Eukaryotic Genetics Group, Biotechnology Research Institute, National Research Council Canada, Montreal, Quebec, Canada
    Mol Gen Genet 249:609-21. 1995
    ..loss of either the Pbs2 (Hog4) MAP kinase kinase required for response to high osmolarity, or loss of the Mkk1 and Mkk2 MAP kinase kinases required for proper cell wall biosynthesis...
  25. pmc Coordination of the mating and cell integrity mitogen-activated protein kinase pathways in Saccharomyces cerevisiae
    B M Buehrer
    Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, 27599 7260, USA
    Mol Cell Biol 17:6517-25. 1997
    ..through the cell integrity phosphorylation cascade and depends on Pkc1 and the redundant MAP/Erk kinases (MEKs), Mkk1 and Mkk2...
  26. doi Improvement in neurological outcome and abolition of cerebrovascular endothelin B and 5-hydroxytryptamine 1B receptor upregulation through mitogen-activated protein kinase kinase 1/2 inhibition after subarachnoid hemorrhage in rats
    Carl Christian Larsen
    Departments of Neurosurgery, Glostrup University Hospital, Glostrup, Denmark
    J Neurosurg 114:1143-53. 2011
    ..The aim in the present study was to determine whether treatment with the MEK1/2 inhibitor U0126 can prevent cerebrovascular receptor upregulation and improve functional outcome after ..
  27. ncbi Atypical protein kinase C-zeta stimulates thyrotropin-independent proliferation in rat thyroid cells
    N Fernandez
    Center for Experimental Therapeutics, University of Pennsylvania School of Medicine, Philadelphia 19104-6160, USA
    Endocrinology 141:146-52. 2000
    ..Interestingly, stimulation of Elk-1 transcriptional activity by MEK1, a p42/p44 MAPK kinase, was significantly enhanced in cells overexpressing PKCzeta...
  28. ncbi [Parathyroid hormone 1-34 induce cardiac myocytes hypertrophy via extracellular regulated protein kinase 1/2 pathway]
    Xiao gang Liu
    Department of Nephrology, Second Hospital, Harbin Medical University, Harbin 150086, China
    Zhonghua Xin Xue Guan Bing Za Zhi 36:439-43. 2008
    To investigate the role of mitogen activated protein kinase kinase 1 (MAPKK, MEK1) and regulated kinase1/2 (ERK1/2) on cardiac hypertrophy induced by rat parathyroid hormone1-34 (rPTH1-34).
  29. ncbi Galectin-3 expression in macrophages is signaled by Ras/MAP kinase pathway and up-regulated by modified lipoproteins
    Koanhoi Kim
    Department of Pathology and Microbiology, University of South Carolina School of Medicine, Columbia, SC 29208, USA
    Biochim Biophys Acta 1641:13-23. 2003
    ..and tyrphostin A25; PD 98059, a selective inhibitor of mitogen-activated protein kinase (MAPK) kinase 1 (MEK1 or MKK1); and SB 203580, a specific inhibitor of p38 MAPK...
  30. pmc Porins from Salmonella enterica serovar Typhimurium activate the transcription factors activating protein 1 and NF-kappaB through the Raf-1-mitogen-activated protein kinase cascade
    Massimiliano Galdiero
    Istituto di Microbiologia, Facolta di Medicina e Chirurgia, Seconda Universita degli Studi di Napoli, 80138 Naples, Italy
    Infect Immun 70:558-68. 2002
    ..the porin-mediated increase in Raf-1 phosphorylation is accompanied by the phosphorylation of MAPK kinase 1/2 (MEK1/2), p38, extracellular-signal-regulated kinase 1/2, and c-Jun N-terminal kinase...
  31. pmc Hypoxia enhances FGF2- and VEGF-stimulated human placental artery endothelial cell proliferation: roles of MEK1/2/ERK1/2 and PI3K/AKT1 pathways
    K Wang
    Department of Obstetrics and Gynecology, Perinatal Research Laboratories, University of Wisconsin, Madison, WI 53715, USA
    Placenta 30:1045-51. 2009
    ..endothelial growth factor (VEGF)-stimulated cell proliferation via the mitogen-activated protein kinase kinase 1/2 (MEK1/2)/extracellular signal-regulated kinases 1/2 (ERK1/2) and phosphatidylinositol-3 kinase (PI3K)/v-akt murine ..
  32. ncbi Calcium-sensing receptor induces proliferation through p38 mitogen-activated protein kinase and phosphatidylinositol 3-kinase but not extracellularly regulated kinase in a model of humoral hypercalcemia of malignancy
    J Tfelt-Hansen
    Division of Endocrinology, Diabetes and Hypertension, Department of Medicine and Membrane Biology Program, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    Endocrinology 145:1211-7. 2004
    ..g. MAPK kinase 1 (MEK1), p38 MAPK, and stress-activated protein kinase 1/c-Jun N-terminal kinase...
  33. ncbi Epicatechin and a cocoa polyphenolic extract modulate gene expression in human Caco-2 cells
    Veronique Noe
    Department of Biochemistry and Molecular Biology, School of Pharmacy, University of Barcelona, E 08028 Barcelona, Spain
    J Nutr 134:2509-16. 2004
    ..The changes in expression for ferritin heavy polypeptide 1 (FTH1), mitogen-activated protein kinase kinase 1 (MAPKK1), signal transducer and activator of transcription 1 (STAT1), and topoisomerase 1 upon incubation with epicatechin,..
  34. ncbi Constitutively active mitogen-activated protein kinase kinase 1 (MAPKK1) and MAPKK2 mediate similar transcriptional and morphological responses
    S J Mansour
    Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder 80309, USA
    Cell Growth Differ 7:243-50. 1996
    Both mitogen-activated protein kinase kinase 1 (MAPKK1) and MAPKK2 function downstream of the proto-oncogene product Raf in signaling pathways that affect cell proliferation and differentiation...
  35. pmc The novel adipocytokine visfatin exerts direct cardioprotective effects
    Shiang Y Lim
    The Hatter Cardiovascular Institute, University College London Hospital and Medical School, London, United Kingdom
    J Cell Mol Med 12:1395-403. 2008
    ..phosphatidylinositol-3-OH kinase (PI3K)-protein kinase B (Akt) and mitogen-activated protein kinase kinase 1 and 2 (MEK1/2)-extracellular signal-regulated kinase 1 and 2 (Erk 1/2)...
  36. pmc Mitogen-activated protein kinase kinase 1 (MEK1) stabilizes MyoD through direct phosphorylation at tyrosine 156 during myogenic differentiation
    Chulman Jo
    Division of Brain Disease, Center for Biomedical Science, National Institutes of Health, Korea Center for Disease Control and Prevention, 187 Osongsaengmyeong2 ro, Gangoe myeon, Cheongwon Gun, Chungcheongbuk do 363 951, South Korea
    J Biol Chem 286:18903-13. 2011
    Previously, we reported that mitogen-activated protein kinase kinase 1 (MEK1) activated in the mid-stage of skeletal muscle differentiation promotes myogenic differentiation...
  37. pmc Mitogen-activated protein kinase kinase 1/2 inhibitors and 17-allylamino-17-demethoxygeldanamycin synergize to kill human gastrointestinal tumor cells in vitro via suppression of c-FLIP-s levels and activation of CD95
    Margaret A Park
    Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, 401 College Street, Massey Cancer Center, Box 980035, Richmond, VA 23298 0035, USA
    Mol Cancer Ther 7:2633-48. 2008
    Prior studies have noted that inhibitors of mitogen-activated protein kinase (MAPK) kinase 1/2 (MEK1/2) enhanced geldanamycin lethality in malignant hematopoietic cells by promoting mitochondrial dysfunction...
  38. doi MEK1 plays contrary stage-specific roles in skeletal myogenic differentiation
    Chulman Jo
    Center for Biomedical Sciences, National Institute of Health, Korea Center for Disease Control and Prevention, 194 Tongillo, Eunpyeong gu, Seoul, Republic of Korea
    Cell Signal 21:1910-7. 2009
    ..this discrepancy may arise from the stage-specific, different roles of mitogen-activated protein kinase kinase 1 (MEK1)...
  39. ncbi Development of cataractous macrophthalmia in mice expressing an active MEK1 in the lens
    X Gong
    Department of Cell Biology, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA
    Invest Ophthalmol Vis Sci 42:539-48. 2001
    ..To characterize the extracellular signal-regulated kinase (ERK) pathway in the lens and to try to understand how this pathway contributes to lens function and cataractogenesis...
  40. doi Characterization of a novel mitogen-activated protein kinase kinase 1/2 inhibitor with a unique mechanism of action for cancer therapy
    Sherif Daouti
    Discovery Oncology, Discovery Chemistry, and Roche Discovery Technologies, Hoffmann La Roche, Inc, Nutley, New Jersey
    Cancer Res 69:1924-32. 2009
    ..Targeting this pathway represents a promising anticancer strategy. Small molecule inhibitors targeting MEK1/2 have shown promise in the clinic; however, ultimate clinical proof-of-concept remains elusive...
  41. ncbi ERK1/2 achieves sustained activation by stimulating MAPK phosphatase-1 degradation via the ubiquitin-proteasome pathway
    Yun Wei Lin
    Molecular Carcinogenesis Laboratory, Institute of Biotechnology, Department of Life Sciences, National Tsing Hua University, Hsinchu 300, Taiwan, Republic of China
    J Biol Chem 278:21534-41. 2003
    ..activation does not always correlate with its upstream Ras-Raf-mitogen-activated protein kinase kinase 1/2 (MKK1/2) signal cascade in cancer cells, and the mechanism remains elusive...
  42. ncbi Significant neuroprotection against ischemic brain injury by inhibition of the MEK1 protein kinase in mice: exploration of potential mechanism associated with apoptosis
    Xinkang Wang
    Department of Cardiovascular Sciences, Bristol Myers Squibb Company, Wilmington, Delaware 19880 0400, USA
    J Pharmacol Exp Ther 304:172-8. 2003
    b>MEK1/2 is a serine/threonine protein kinase that phosphorylates and activates extracellular signal-responsive kinase (ERK)1/2...
  43. ncbi MEK1 and MEK2 isoforms regulate distinct functions in pancreatic cancer cells
    Lei Zhou
    Department of Hepato pancreato biliary Tumour Surgery, China Medical University Shengjing Hospital, Shenyang, PR China
    Oncol Rep 24:251-5. 2010
    The mitogen-activated protein kinase kinase 1/2 (MEK1/2) signalling pathway plays a central role in tumour progression. Small molecules that inhibit MEK1/2 are therefore considered attractive candidates for anti-cancer drugs...
  44. ncbi A new cellular signaling mechanism for angiotensin II activation of NF-kappaB: An IkappaB-independent, RSK-mediated phosphorylation of p65
    Liping Zhang
    Department of Internal Medicine, The University of Texas Medical Branch, Galveston 77555 1064, USA
    Arterioscler Thromb Vasc Biol 25:1148-53. 2005
    ..We examined the signaling mechanism whereby Ang II activates NF-kappaB in vascular smooth muscle cells (VSMCs)...
  45. ncbi Biological characterization of ARRY-142886 (AZD6244), a potent, highly selective mitogen-activated protein kinase kinase 1/2 inhibitor
    Tammie C Yeh
    Array BioPharma, Inc, Boulder, Colorado 80301, USA
    Clin Cancer Res 13:1576-83. 2007
    ..We have developed a highly potent and selective inhibitor of MEK1/2...
  46. ncbi BRAF and MEK mutations make a late entrance
    Nick Duesbery
    Van Andel Institute, 333 Bostwick Avenue NE, Grand Rapids, MI 49503, USA
    Sci STKE 2006:pe15. 2006 a mitogen-activated protein kinase kinase kinase (MAPKKK), and mitogen-activated protein kinase kinase 1 and 2 (MAPKK1/2, also known as MKK1/2 or MEK1/2) are signaling partners in the MAPK signal transduction pathway...
  47. pmc MEK1 protein kinase inhibition protects against damage resulting from focal cerebral ischemia
    A Alessandrini
    Medical Services, Massachusetts General Hospital, Charlestown, MA 02129, USA
    Proc Natl Acad Sci U S A 96:12866-9. 1999
    The MEK1 (MAP kinase/ERK kinase)/ERK (extracellular-signal-responsive kinase) pathway has been implicated in cell growth and differentiation [Seger, R. & Krebs, E. G. (1995) FASEB J. 9, 726-735]...
  48. pmc Colorectal cancer cells with the BRAF(V600E) mutation are addicted to the ERK1/2 pathway for growth factor-independent survival and repression of BIM
    J A Wickenden
    Laboratory of Molecular Signalling, The Babraham Institute, Babraham Research Campus, Babraham, Cambridge, UK
    Oncogene 27:7150-61. 2008
    The RAF-mitogen-activated protein kinase kinase 1/2-extracellular signal-regulated kinase 1/2 (RAF-MEK1/2-ERK1/2) pathway is activated in many human tumours and can protect cells against growth factor deprivation; however, most such ..
  49. pmc PAK1 phosphorylation of MEK1 regulates fibronectin-stimulated MAPK activation
    Jill K Slack-Davis
    Department of Microbiology, University of Virginia Health System, Charlottesville, VA 22908, USA
    J Cell Biol 162:281-91. 2003
    ..Here, we provide evidence that phosphorylation of S298 of MAPK kinase 1 (MEK1) by p21-activated kinase (PAK) is a site of convergence for integrin and growth factor signaling...
  50. doi Molecular characterisation of MEK1/2- and MKK3/6-like mitogen-activated protein kinase kinases (MAPKK) from the fox tapeworm Echinococcus multilocularis
    Verena Gelmedin
    University of Wurzburg, Institute of Hygiene and Microbiology, Wurzburg, Germany
    Int J Parasitol 40:555-67. 2010
    ..Structurally, EmMKK1 and EmMKK2 closely resemble members of the MKK3/6- and the MEK1/2-MAPKK sub-families, respectively, from a variety of vertebrate and invertebrate organisms, and contain all ..
  51. ncbi Gonadotropin regulation of testosterone production by primary cultured theca and granulosa cells of Atlantic croaker: II. Involvement of a mitogen-activated protein kinase pathway
    Abby D Benninghoff
    Department of Marine Science, University of Texas at Austin, 750 Channel View Drive, Port Aransas, TX 78373, USA
    Gen Comp Endocrinol 147:288-96. 2006
    ..testosterone synthesis was markedly attenuated by two antagonists of mitogen-activated protein kinase kinases 1/2 (MEK1/2, also known as Map2k1/Map2k2)...
  52. ncbi Constitutively active mutant of the mitogen-activated protein kinase kinase MEK1 induces epithelial dedifferentiation and growth inhibition in madin-darby canine kidney-C7 cells
    H Schramek
    Department of Physiology, University of Innsbruck, A 6010 Innsbruck, Austria
    J Biol Chem 272:11426-33. 1997
    ..In the present study, we used a constitutively active MAPK/extracellular signal-regulated kinase (ERK) kinase 1 (MEK1) mutant to investigate the function of the highly conserved MEK1-ERK2 signaling module in renal epithelial cell ..
  53. pmc Arabidopsis mitogen-activated protein kinase kinases MKK1 and MKK2 have overlapping functions in defense signaling mediated by MEKK1, MPK4, and MKS1
    Jin Long Qiu
    Department of Biology, University of Copenhagen, 2200 Copenhagen N, Denmark
    Plant Physiol 148:212-22. 2008
    The Arabidopsis (Arabidopsis thaliana) MKK1 and MKK2 mitogen-activated protein kinase kinases have been implicated in biotic and abiotic stress responses as part of a signaling cascade including MEKK1 and MPK4...
  54. ncbi Differential expression of MEK1 and MEK2 during mouse development
    A Alessandrini
    Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA
    Cell Growth Differ 8:505-11. 1997
    Map/Erk kinase 1 (MEK1) and MEK2 activate the Erk/ MAP kinases and have been implicated in cell growth and differentiation...
  55. ncbi Protein kinase C-zeta and phosphoinositide-dependent protein kinase-1 are required for insulin-induced activation of ERK in rat adipocytes
    M P Sajan
    J. A. Haley Veterans Hospital Research Service, Department of Internal Medicine, University of South Florida College of Medicine, Tampa, Florida 33612, USA
    J Biol Chem 274:30495-500. 1999
    ..we found that a tyrosine kinase (presumably the insulin receptor), the SH2 domain of GRB2, SOS, RAS, RAF, and MEK1 were required for insulin effects on ERK in the rat adipocyte...
  56. ncbi Relationship between activation of epidermal growth factor receptor and cell dissociation in pancreatic cancer
    Xiaodong Tan
    Department of Surgery II, Kumamoto University Medical School, Honjo 1 1 1, Kumamoto 860 8556, Japan
    Int J Oncol 25:1303-9. 2004
    ..expressions of epidermal growth factor receptor (EGFR), phosphorylated EGFR (p-EGFR), and its downstream kinases MEK1/2 and ERK1/2, were analyzed to clarify the regulatory mechanism of cell dissociation in pancreatic cancer cells...
  57. ncbi Analysis of invasion-metastasis mechanism in pancreatic cancer: involvement of tight junction transmembrane protein occludin and MEK/ERK signal transduction pathway in cancer cell dissociation
    Xiaodong Tan
    Department of Surgery II, Kumamoto University Medical School, Kumamoto, Japan
    Oncol Rep 11:993-8. 2004
    ..and CAPAN-2) pancreatic cancer cell lines were analyzed immunocytochemically with anti-occludin, phosphorylated MEK1/2 (p-MEK1/2), phosphorylated ERK1/2 (p-ERK1/2) antibodies...
  58. ncbi Arrangement of expression and distribution of tight junction protein claudin-1 in cell dissociation of pancreatic cancer cells
    Xiaodong Tan
    Department of Surgery II, Kumamoto University Medical School, Kumamoto, Japan
    Int J Oncol 25:1567-74. 2004
    ..and Western blot analysis were performed in pancreatic cancer cells using anti-claudin-1, MEK2 and phosphorylated MEK1/2 (p-MEK1/2) antibodies to reveal the correlation between TJ and cancer cell dissociation, as well as the ..
  59. pmc Identification and characterization of a new mammalian mitogen-activated protein kinase kinase, MKK2
    J Wu
    Department of Internal Medicine, University of Virginia Health Sciences Center, Charlottesville 22908
    Mol Cell Biol 13:4539-48. 1993
    ..A MAP kinase kinase (MKK1 or MEK1) has been identified as a dual-specificity protein kinase that is sufficient to phosphorylate MAP kinases ..
  60. pmc Activation of Erk and JNK MAPK pathways by acute swim stress in rat brain regions
    Chang peng Shen
    Department of Psychiatry, New York University School of Medicine, 550 First Ave, MHL HN511, New York, NY 10016, USA
    BMC Neurosci 5:36. 2004
    ..on the phosphorylation state of the upstream activators of the MAPKs, their respective MAPK kinases (MAPKKs; P-MEK1/2, P-MKK4 and P-MKK3/6), were determined...
  61. pmc Role of ERK/MAPK in endothelin receptor signaling in human aortic smooth muscle cells
    Qing wen Chen
    Division of Experimental Vascular Research, Institute of Clinical Science in Lund, Lund University, Lund, Sweden
    BMC Cell Biol 10:52. 2009
    ..This study was designed to investigate the ETA and ETB receptor intracellular signaling in human VSMCs and used phosphorylation (activation) of ERK1/2 as a functional signal molecule for endothelin receptor activity...
  62. ncbi Preferential involvement of MEK1 in the tumor necrosis factor-alpha-induced activation of p42mapk/erk2 in mouse macrophages
    B W Winston
    Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206, USA
    J Biol Chem 270:27391-4. 1995
    ..In this study, we investigated the preferential involvement of the MEK isoforms MEK1 and MEK2 in the activation of p42mapk/erk2 in mouse macrophages stimulated with TNF alpha...
  63. ncbi Functional role of alpha-actinin, PI 3-kinase and MEK1/2 in insulin-like growth factor I receptor kinase regulated motility of human breast carcinoma cells
    Marina A Guvakova
    Department of Microbiology, University of Pennsylvania, 3610 Hamilton Walk, 211 Johnson Pavilion, Philadelphia PA 19104, USA
    J Cell Sci 115:4149-65. 2002
    ..The activity of MEK1/2 kinases was needed for consecutive cell migration. This work also defined a new function for alpha-actinin...
  64. ncbi [The role of mitogen-activated protein kinase cascades in inhibition of proliferation in human prostate carcinoma cells by raloxifene: an in vitro experiment]
    Yu xi Zhang
    Department of Urology, First Affiliated Hospital, China Medical University, Shenyang 110001, China
    Zhonghua Yi Xue Za Zhi 88:271-5. 2008
    ..To investigate the role of mitogen-activated protein kinase (MAPK) in the apoptosis and cell cycle arrest of human prostate carcinoma cells induced by raloxifene (RAL)...
  65. ncbi Regulation of intracellular MEK1/2 translocation in mouse oocytes: cytoplasmic dynein/dynactin-mediated poleward transport and cyclin B degradation-dependent release from spindle poles
    Bo Xiong
    State Key Laboratory of Reproductive Biology, Institute of Zoology and Graduate School, Chinese Academy of Sciences, Beijing, PR China
    Cell Cycle 6:1521-7. 2007
    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...
  66. pmc Inactivation of dual-specificity phosphatases is involved in the regulation of extracellular signal-regulated kinases by heat shock and hsp72
    Julia Yaglom
    Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02118, USA
    Mol Cell Biol 23:3813-24. 2003
    ..demonstrated that heat shock activates ERKs via two distinct mechanisms: stimulation of the ERK-activating kinases, MEK1/2, and inhibition of ERK dephosphorylation...
  67. pmc Novel changes in NF-{kappa}B activity during progression and regression phases of hyperplasia: role of MEK, ERK, and p38
    Parthasarathy Chandrakesan
    Department of Internal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA
    J Biol Chem 285:33485-98. 2010
    ..Phosphorylation of MEK1/2 (Ser(217/221)), ERK1/2 (Thr(202)/Tyr(204)), and p38 (Thr(180)/Tyr(182)) paralleled IKKα/β kinetics at days 6 ..
  68. ncbi Regulation of meiotic progression by the meiosis-specific checkpoint kinase Mek1 in fission yeast
    Livia Perez-Hidalgo
    Centro de Investigacion del Cancer, CSIC University of Salamanca, Campus Unamuno, 37007 Salamanca, Spain
    J Cell Sci 116:259-71. 2003
    ..Here, we describe a role for a meiosis-specific kinase, Mek1, in the meiotic recombination checkpoint in fission yeast...
  69. pmc Constitutive activation of MEK1 in chondrocytes causes Stat1-independent achondroplasia-like dwarfism and rescues the Fgfr3-deficient mouse phenotype
    Shunichi Murakami
    Department of Molecular Genetics, The University of Texas, MD Anderson Cancer Center, Houston, Texas 77030, USA
    Genes Dev 18:290-305. 2004
    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...
  70. ncbi Receptor-mediated tobacco toxicity: cooperation of the Ras/Raf-1/MEK1/ERK and JAK-2/STAT-3 pathways downstream of alpha7 nicotinic receptor in oral keratinocytes
    Juan Arredondo
    Department of Dermatology, University of California Davis, Sacramento, CA, USA
    FASEB J 20:2093-101. 2006
    ..The use of pathway inhibitors revealed that signaling through the Ras/Raf-1/MEK1/ERK steps mediated alpha7-dependent up-regulation of STAT-3...
  71. ncbi AG-041R stimulates cartilage matrix synthesis without promoting terminal differentiation in rat articular chondrocytes
    M Okazaki
    Fuji Gotemba Research Laboratories, Chugai Pharmaceutical Co, Ltd, 1 135 Komakado, Gotemba, Shizuoka 412 8513, Japan
    Osteoarthritis Cartilage 11:122-32. 2003
    ..AG-041R, a novel indolin-2-one derivative, has recently been demonstrated to induce systemic hyaline cartilage hyperplasia in rats. The aim of this study was to characterize its anabolic actions on chondrocytes...
  72. ncbi Myricetin is a novel natural inhibitor of neoplastic cell transformation and MEK1
    Ki Won Lee
    Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, MN 55912, USA
    Carcinogenesis 28:1918-27. 2007
    ..that 3,3',4',5,5',7-hexahydroxyflavone (myricetin), one of the major flavonols in red wine, is a novel inhibitor of MEK1 activity and transformation of JB6 P+ mouse epidermal cells...
  73. pmc Bypass of a meiotic checkpoint by overproduction of meiotic chromosomal proteins
    J M Bailis
    Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520 8103, USA
    Mol Cell Biol 20:4838-48. 2000
    ..Overproduction of either the meiotic chromosomal protein Red1 or the meiotic kinase Mek1 bypasses this checkpoint, allowing zip1 cells to sporulate...
  74. ncbi Further delineation of the phenotype resulting from BRAF or MEK1 germline mutations helps differentiate cardio-facio-cutaneous syndrome from Costello syndrome
    Karen W Gripp
    Division of Medical Genetics, A I duPont Hospital for Children Nemours Childrens Clinic, Wilmington, DE 19899, USA
    Am J Med Genet A 143:1472-80. 2007
    ..The recent discoveries of germline HRAS mutations in patients with Costello syndrome and mutations in BRAF, MEK1, and MEK2 in CFC syndrome uncovered the biologic mechanism for the shared phenotypic findings based on the close ..
  75. doi Dose-dependent effect of intracerebroventricular injection of ouabain on the phosphorylation of the MEK1/2-ERK1/2-p90RSK pathway in the rat brain related to locomotor activity
    Se Hyun Kim
    Department of Psychiatry and Behavioral Science, Seoul National University College of Medicine, Clinical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea
    Prog Neuropsychopharmacol Biol Psychiatry 32:1637-42. 2008
    ..of ouabain in rats, we investigated changes in the phosphorylation of mitogen-activated protein kinase kinase1/2 (MEK1/2), ERK1/2, and p90 ribosomal s6 kinase (p90RSK) in rat striatum, frontal cortex, and hippocampus along with ..
  76. pmc Mek1 kinase is regulated to suppress double-strand break repair between sister chromatids during budding yeast meiosis
    Hengyao Niu
    Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794 5215, USA
    Mol Cell Biol 27:5456-67. 2007
    b>Mek1 is a meiosis-specific kinase in budding yeast which promotes recombination between homologous chromosomes by suppressing double-strand break (DSB) repair between sister chromatids...
  77. ncbi Epidermal growth factor induces c-fos and c-jun mRNA via Raf-1/MEK1/ERK-dependent and -independent pathways in bovine luteal cells
    Dong Bao Chen
    The Women s Research Institute, Department of Obstetrics and Gynecology, University of Kansas School of Medicine Wichita, 1010 North Kansas, Wichita 67214, USA
    Mol Cell Endocrinol 200:141-54. 2003
    ..Activation of Raf resulted in the phosphorylation and activation of MAPK kinase (MEK1) which subsequently activated ERKs...
  78. ncbi Clozapine and the mitogen-activated protein kinase signal transduction pathway: implications for antipsychotic actions
    Jeff L Browning
    Department of Psychiatry, Scott and White Memorial Hospital, Central Texas Veterans Health Care System, and Texas A and M University System Health Science Center College of Medicine, Temple, Texas, USA
    Biol Psychiatry 57:617-23. 2005
  79. ncbi Role of osteoclast extracellular signal-regulated kinase (ERK) in cell survival and maintenance of cell polarity
    Hiroaki Nakamura
    Department of Oral Morphology, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan
    J Bone Miner Res 18:1198-205. 2003
    Morphological changes of osteoclasts by a MEK1 inhibitor, PD98059, were investigated to clarify a role of ERK. PD98059 promoted apoptosis of osteoclasts and the loss of ruffled borders...
  80. doi Selective adenosine A2a receptor antagonism reduces JNK activation in oligodendrocytes after cerebral ischaemia
    Alessia Melani
    Department of Preclinical and Clinical Pharmacology, University of Florence, Viale Pieraccini, 6, Florence, Italy
    Brain 132:1480-95. 2009
    ..objective of the present study was to investigate whether the adenosine A(2A) antagonist SCH58261 affects JNK and MEK1/ERK MAPK activation...
  81. doi Nuclear envelope localization of Ran-binding protein 2 and Ran-GTPase-activating protein 1 in psoriatic epidermal keratinocytes
    Kayo Yasuda
    Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
    Exp Dermatol 23:119-24. 2014
    ..Therefore, we treated HaCaT cells with inhibitors to disrupt the MAP kinase kinase 1 (MEK1), PI3-kinase, or mTOR pathways...
  82. ncbi Requirement for a hsp90 chaperone-dependent MEK1/2-ERK pathway for B cell antigen receptor-induced cyclin D2 expression in mature B lymphocytes
    Michael J Piatelli
    Department of Biology, Boston College, Chestnut Hill, Massachusetts 02467, USA
    J Biol Chem 277:12144-50. 2002
    ..Inhibition of the MEK1/2-ERK pathway was sufficient to abrogate BCR-induced cyclin D2 expression at the mRNA and protein levels...
  83. ncbi Activation of mitogen-activated protein kinase cascade regulates pituitary tumor-transforming gene transactivation function
    L Pei
    Division of Endocrinology and Metabolism, Cedars Sinai Research Institute UCLA School of Medicine, Los Angeles, California 90048, USA
    J Biol Chem 275:31191-8. 2000 epidermal growth factor or an expression vector for a constitutively active form of the MAP kinase kinase (MEK1) led to stimulation of PTTG transactivation activity...
  84. doi Taiwan cobra phospholipase A2 elicits posttranscriptional up-regulation of ADAM17 in human neuroblastoma SK-N-SH cells
    Wen Hsin Liu
    Institute of Biomedical Sciences, National Sun Yat Sen University Kaohsiung Medical University Joint Research Center, National Sun Yat Sen University, Kaohsiung 804, Taiwan
    J Cell Biochem 111:148-57. 2010
    ..abolished posttranscriptional up-regulation of ADAM17 in PLA(2)-treated cells, while treatment with U0126 (MEK1 and MEK2 inhibitor) increased ADAM17 maturation in SK-N-SH cells...
  85. pmc β-Arrestins regulate human cardiac fibroblast transformation and collagen synthesis in adverse ventricular remodeling
    Jinju Li
    Department of Surgery, Section of Cardiac and Thoracic Surgery, The University of Chicago Medical Center, Chicago, IL, USA
    J Mol Cell Cardiol 76:73-83. 2014
    ..This was prevented by pre-treatment with a MEK1/2 inhibitor...
  86. pmc CInQ-03, a novel allosteric MEK inhibitor, suppresses cancer growth in vitro and in vivo
    Dong Joon Kim
    The Hormel Institute, University of Minnesota, Austin, MN 55912, USA
    Carcinogenesis 34:1134-43. 2013
    ..All three inhibitors were highly effective in suppressing MEK1 and MEK2 in vitro kinase activity as well as anchorage-dependent and anchorage-independent cell growth...
  87. doi Increase of MCP-1 (CCL2) in myelin mutant Schwann cells is mediated by MEK-ERK signaling pathway
    Stefan Fischer
    Department of Neurology, Developmental Neurobiology, University of Wuerzburg, Wuerzburg, Germany
    Glia 56:836-43. 2008
    ..nerve lysates the MAP-kinases extracellular signal-regulated kinase 1/2 (ERK1/2) and MAP kinase/ERK kinase 1/2 (MEK1/2) showed an early and constantly increasing activation in P0 mutants...
  88. ncbi Inhibitors of MEK1/2 interact with UCN-01 to induce apoptosis and reduce colony formation in mammary and prostate carcinoma cells
    Robert McKinstry
    Department of Radiation Oncology, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298, USA
    Cancer Biol Ther 1:243-53. 2002
    ..We therefore investigated the impact of combined exposure to the check-point abrogator (UCN-01) in conjunction with MEK1/2 inhibitors upon survival of breast and prostate carcinoma cells...
  89. ncbi Helicobacter pylori activates the proto-oncogene c-fos through SRE transactivation
    Yuzo Mitsuno
    Department of Gastroenterology, University of Tokyo, 7 3 1 Hongo, Bunkyo ku, Tokyo 113 8655, Japan
    Biochem Biophys Res Commun 291:868-74. 2002
    ..H. pylori-mediated c-fos promoter activation was inhibited by MEK1/2 inhibitor (U0126)...
  90. doi Lopinavir inhibits meningioma cell proliferation by Akt independent mechanism
    Mahlon D Johnson
    Division of Neuropathology, Department of Pathology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
    J Neurooncol 101:441-8. 2011
    ..Lopinavir effects on basal and PDGF-stimulated phosphorylation of the Akt-mTOR, MEK1/2-MAPK and STAT3 pathways, phosphorylation of Rb, Caspase 3 activation and reductions in survivin were assessed by ..
  91. pmc Interdependence of platelet-derived growth factor and estrogen-signaling pathways in inducing neonatal rat testicular gonocytes proliferation
    Raphael Thuillier
    Department of Biochemistry and Molecular and Cellular Biology, Georgetown University Medical Center, Washington, District of Columbia, USA
    Biol Reprod 82:825-36. 2010
    ..Thus, the inappropriate exposure of gonocytes to xenoestrogens might disrupt the crosstalk between the two pathways and potentially interfere with gonocyte development...
  92. doi Regulation of hepatitis C virus replication and gene expression by the MAPK-ERK pathway
    Rongjuan Pei
    Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China
    Virol Sin 27:278-85. 2012
    ..It could be shown that the MAPK-ERK inhibitors are able to partially modulate the expression of interferon-stimulated genes...
  93. ncbi Pachytene exit controlled by reversal of Mek1-dependent phosphorylation
    J M Bailis
    Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut 06520, USA
    Cell 101:211-21. 2000
    ..This pachytene checkpoint requires two meiotic chromosomal proteins, Red1 and Mek1; Mek1 is a kinase that phosphorylates Red1...
  94. pmc Essential role for endocytosis in the growth factor-stimulated activation of ERK1/2 in endothelial cells
    Morgane Gourlaouen
    Tumour Biology Team, Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London SW3 6JB, United Kingdom
    J Biol Chem 288:7467-80. 2013
    ..Activation of VEGFR2 and C-Raf still occurred in the presence of the inhibitors, whereas the activation of MEK1/2 and ERK1/2 was abrogated...
  95. doi Cigarette smoke particle-phase extract induces HO-1 expression in human tracheal smooth muscle cells: role of the c-Src/NADPH oxidase/MAPK/Nrf2 signaling pathway
    Shin Ei Cheng
    Department of Physiology and Pharmacology, Chang Gung University, Kwei San, Tao Yuan 33302, Taiwan
    Free Radic Biol Med 48:1410-22. 2010
    ..and inhibitors of c-Src (PP1), NADPH oxidase [diphenylene iodonium chloride (DPI) and apocynin (APO)], MEK1/2 (U0126), p38 MAPK (SB202190), and JNK1/2 (SP600125) or transfection with siRNAs for Src, p47(phox), NOX2, p42, ..
  96. doi Insulin regulates glucagon-like peptide-1 secretion from the enteroendocrine L cell
    Gareth E Lim
    Department of Physiology, University of Toronto, Toronto, Ontario, Canada
    Endocrinology 150:580-91. 2009
    ..secretion was abrogated by inhibiting the MEK-ERK1/2 pathway with PD98059 or by overexpression of a kinase-dead MEK1-ERK2 fusion protein...
  97. pmc Cross-cascade activation of ERKs and ternary complex factors by Rho family proteins
    J A Frost
    U T Southwestern Medical Center, Department of Pharmacology, Dallas 75235 9041, USA
    EMBO J 16:6426-38. 1997
    ..Examination of ERK pathway kinases shows that neither MEK1 nor Ras will synergize with Rho-type proteins, and that only MEK1 is fully activated, indicating that MEKs are a ..
  98. ncbi Involvement of p42/p44 MAPK, p38 MAPK, JNK, and NF-kappaB in IL-1beta-induced VCAM-1 expression in human tracheal smooth muscle cells
    Chien Chun Wang
    Graduate Institute of Natural Products, Department of Pharmacology, 259 Wen Hwa 1st Road, Chang Gung University, Kwei San, Tao Yuan, Taiwan
    Am J Physiol Lung Cell Mol Physiol 288:L227-37. 2005
    ..of VCAM-1 protein and mRNA in a time-dependent manner, which was significantly inhibited by inhibitors of MEK1/2 (U0126 and PD-98059), p38 (SB-202190), and c-Jun NH(2)-terminal kinase (JNK; SP-600125)...
  99. ncbi Effects of anti-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene on human small airway epithelial cells and the protective effects of myo-inositol
    H Jyonouchi
    Department of Pediatrics, University of Minnesota, School of Medicine, UMHC, Minneapolis 55455, USA
    Carcinogenesis 20:139-45. 1999
    ..a phosphatidylinositol-3 kinase (PI-3K) inhibitor, and PD98059, a mitogen activated protein kinase (MAPK) kinase-1 (MEK1) inhibitor, but not by SB202190, a p38 MAPK inhibitor, or melittin, a protein kinase C inhibitor...
  100. pmc Multiple giant cell lesions in patients with Noonan syndrome and cardio-facio-cutaneous syndrome
    Thomas E Neumann
    1Department of Human Genetics, University Hospital Munster, Munster, Germany
    Eur J Hum Genet 17:420-5. 2009
    ..with mutations in the genes PTPN11, SOS1, RAF1, or KRAS, whereas CFCS can be caused by mutations in BRAF, MEK1, MEK2, or KRAS...
  101. doi [Alpha-1 Antitrypsin Affects U0126-Induced Cytotoxicity in Colon Cancer Cell Line (HCT116)]
    M Ljujic
    Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia
    Mol Biol (Mosk) 50:174-8. 2016
    ..The presence of AAT in the HCT116 cell culture antagonized cytotoxicity of blockers of MEK1/2, PI3K/Akt pathways as well as NF-κB...

Research Grants62

    Bradford C Berk; Fiscal Year: 2012
    ..Then we showed that GIT1 is a scaffold for several key pathways including PLC3-CamKII , MEK1-ERK1/2, and PIX-PAK...
    Nancy M Hollingsworth; Fiscal Year: 2013
    ..In meiosis, programmed DSBs instead activate the meiosis-specific Mek1 kinase...
  3. Linkage of Lung Inflammation to 8-oxoguanine and OGG1
    ISTVAN STEVEN BOLDOGH; Fiscal Year: 2013
    ..that EG8-oxoG increased the levels of 1) activated small GTPases;2) Ras to Raf-1 binding;and phosphorylation of 3) MEK1,2;4) ERK1,2;and 5) RelA-Ser276. EG8-oxoG induced luciferase expression driven from the CXCL-8 promoter...
  4. Mechanism of Action of Prohibitin in Ovarian Cell Function
    Winston E Thompson; Fiscal Year: 2013
    ..PHB1 is phosphorylated on Y249 in a MEK1-dependent fashion while PHB1 is required for ERK1/2 activation defining a new regulatory paradigm in response to ..
  5. Interaction of cationic lipids with dendritic cells
    Leaf Huang; Fiscal Year: 2012
    ..P38 activation leads to the production of IL-12. Inhibition of pERK activation by specific inhibitors of Mek1/2, the upstream kinase which phosphorylates ERK, inhibited CCL2 production and, more importantly, the antitumor ..
  6. Copper reduction as a novel therapy in BRAF-mutant positive cancers
    Donita C Brady; Fiscal Year: 2013
    ..To that end, my proposed research project evolved from our previous observations that copper (Cu) influx enhances MEK1 phosphorylation of its substrates ERK1/2 through a Cu-MEK1 interaction...
  7. Defining mechanisms of MEK1/2 inhibitor response in triple negative breast cancer
    Martin Whittle; Fiscal Year: 2013
    ..The observation of high RAF/MEK/ERK activity in many TNBC patient samples has prompted the investigation of using MEK1/2 inhibitors as a potential therapeutic strategy...
  8. Apoptosis Induced by Glucocorticoids and MEK1/2 Inhibitors in Leukemia
    Hisashi Harada; Fiscal Year: 2012
    ..abstract_text> ..
  9. Translational Control in Long-Term Synaptic Plasticity
    RAYMOND KELLEHER; Fiscal Year: 2009
    ..In the present application, conditional expression of a dominant-negative form of MEK1 in the post-natal murine forebrain is shown to inhibit ERK activation and cause selective deficits in hippocampal ..
  10. The IKK/Tpl2 axis of TLR signaling
    Shao Cong Sun; Fiscal Year: 2013
    ..inhibitor I(B, whereas Tpl2 is a MAP3K that activates the MAP kinase ERK through phosphorylating the ERK kinase, MEK1. Interestingly, Tpl2 is sequestered by an I(B-like molecule, p105, and the activation of Tpl2 requires IKK-mediated ..
  11. Dose-dependent Activation of the MEK/ERK Pathway in Hematopoiesis
    Jing Zhang; Fiscal Year: 2013
    ..To further test our hypothesis in vivo, we have generated a novel conditional MEK1 knockin allele carrying point mutations that mimic phosphorylation at serine 218 and serine 222 (LSL MEK1 S218;222E)..
  12. A Proteomics-based Approach to Identifying Mechanisms of Drug Resistance to Targe
    Scott Stuart; Fiscal Year: 2010
    ..method to profile MEK-dependent phosphorylation events in a number of metastatic melanoma cell lines using the MEK1/2 inhibitor AZD6244...
    Andrew Catling; Fiscal Year: 2009
    ..We will focus on MEK1 phosphorylation and assembly of MEKl-specific signaling complexes as points of integration for adhesion and growth ..
    Melanie Cobb; Fiscal Year: 2006
    ..The ERK2 activator MEK1 binds to molecules other than ERK1/2 and Raf that are essential for signal transmission through the cascade...
  15. Oklahoma Autoimmunity Center of Excellence
    Judith A James; Fiscal Year: 2013
    ..The second tests the efficacy and early MRI changes of a novel MEK1/MEK2 inhibitor in RA with additional mechanistic studies...
    William E Whitehead; Fiscal Year: 2012
    ..Identifying these different phenotypes of IBS and the genetic markers associated with them may help to identify new targets for drug development and may help us to individualize treatment and thereby make it more successful. ..
  17. Pancreatic Cancer Management by Novel Gene Therapy &Dietary Agents
    Paul B Fisher; Fiscal Year: 2012
    ..When K-ras expression or its downstream MEK1/MEK2 pathway is inhibited or a reactive oxygen species (ROS) inducer is applied, mda-7/IL-24 mRNA is converted into ..
  18. Peri-arteriolar Myofibroblast Differentiation in the Pathobiology of IPAH
    ARTHUR ROGER STRAUCH; Fiscal Year: 2012 over-active PI3K/Akt feed-forward signaling kinases and/or impaired feed-back inhibition mediated by sub-optimal MEK1/Erk1,2/Egr-1 signaling...
  19. The role of Raf-MEK signaling in the pathogenesis of hypertrophic cardiomyopathy
    JASON BECKER; Fiscal Year: 2013
    ..We discovered that mitogen-activated protein kinase kinase (MEK1/2) was important in the pathological induction of this signaling pathway...
  20. Studying the initiation, progression and therapy of lung cancer in mouse models
    Martin McMahon; Fiscal Year: 2013
    ..the anti-tumor effects of potent, specific and selective pharmacological inhibitors of either RAF (SB590885) or MEK1/2 (PD0325901) using the KRasLSL mouse model of lung tumorigenesis...
  21. Manipulation of inflammasomes and NF-kB signaling in human myeloid cells by Myxom
    Grant McFadden; Fiscal Year: 2013
    ..response to MYXV infection;study the co-ordinating upstream role of virus-induced MAPK, in particular the role of MEK1/2-ERK1/2 kinases, in co-inducing both the type I IFN and pro-inflammatory cytokine signaling pathways in response ..
  22. Novel pathways modulating Raf-mediated cardiac hypertrophy
    Matthew J Wolf; Fiscal Year: 2013
    ..Moreover, the activation of EGFR and subsequent signals to the small GTPase, Ras, and the kinases, Raf and MEK1, cause cardiac hypertrophy in flies and mammals...
  23. Role of MEK1 in T cell function in asthma
    Rafeul Alam; Fiscal Year: 2013
    ..refractoriness we observed that T cells from asthmatic patients express increased levels of the signaling kinase MEK1, which stimulates IL-2 production. Interestingly, IL-2 directly induces MEK1...
  24. Role of PAR-1 and PAR-2 in Cardiac Remodeling
    Nigel Mackman; Fiscal Year: 2010
    ..Specific Aim 2 will evaluate the role of the MEK5-ERK5, MEK1-ERK1/2 and calcineurin signaling pathways in PAR-1- and PAR-2-dependent hypertrophy of cultured cardiomyocytes by ..
  25. The Molecular Basis of OX40 on CD4 T Cells
    Michael Croft; Fiscal Year: 2012
    ..Specifically, we will determine whether OX40 utilizes PKC0, PDK1, and MEK1/ERK to target Akt and NF-KB, and how these signaling cascades impact the expression and function of survivin and ..
  26. The Ras/Mapk pathway in cardiovascular disease.
    Forest M White; Fiscal Year: 2013
    ..Costello Syndrome (CS), caused by HRAS mutations, and Cardio-Facial- Cutaneous-Syndrome (CFCS) (caused by BRAF, MEK1 or MEK2 mutations)...
  27. TSC1-mTOR signaling and T cell tolerance
    XIAOPING ZHONG; Fiscal Year: 2013
    ..Using genetically manipulated mice and cell line models, we have recently revealed that the RasGRP1-Ras- Mek1/2-Erk1/2 pathway is critical for both mTORC1 and mTORC2 activation in T cells following T cell receptor (TCR) ..
  28. In-cell NMR technology to study protein interactions
    Alexander Shekhtman; Fiscal Year: 2013
    ..plasmid constructs capable of overexpressing viral HIV p6 domain, endocytic proteins TSG101 and Hrs, protein kinase MEK1 and ERK2, and monoubiquitination machinery in bacteria...
  29. Preclinical Development of Novel MEK1/2 Inhibitors to Treat Inherited Cardiomyopa
    Uday R Khire; Fiscal Year: 2013
    ..The research at Columbia has further shown that inhibitors of MAPK/ERK kinase1/2 (MEK1/2), the enzyme that activates ERK1/2, prevent ventricular dilatation, improve cardiac contractility and delay the ..
    Paul Dent; Fiscal Year: 2013
    ..We also have published data demonstrating that geldanamycins (17AAG, 17DMAG) + MEK1/2 inhibitors synergize to kill liver and pancreatic tumor cells via CD95 activation...
  31. ERK signaling and a hybrid surgical/molecular approach for chronic heart failure
    Michael J Mann; Fiscal Year: 2013
    ..studies, we will test this translational hypothesis utilizing a new and unique genetic model of regulatable MEK1-ERK1/2 signaling...
  32. Kinome Reprogramming in Response to Targeted Kinase Inhibitors
    Gary L Johnson; Fiscal Year: 2013
    ..MIB/MS identified a kinome response signature to a select MEK1/2 inhibitor AZD6244 that is currently in clinical testing for triple negative breast cancer...
  33. Checkpoint Abrogation and MEK 1/2 Inhibition in Myeloma
    Steven Grant; Fiscal Year: 2013
    ..period, important new insights emerged, including the observations that a) disruption of Chk1 by UCN-01 activates MEK1/2/ERK1/2 through a Ras- dependent mechanism that limits lethality;b) these findings may represent a generalized ..
    Gregory Springett; Fiscal Year: 2013
    ..Aim 2, we will determine whether LPAAT-[unreadable] is required for, and/or cooperates with, RalGDS/RalA/B, Raf-1/Mek1/2 or PI3K/Akt pathways to transform immortalized human primary epithelial cells...
  35. The Impact of TLR on Intestinal Tumorigenesis
    Eyal Raz; Fiscal Year: 2010
    ..We will treat these animals with UO126 (a MEK1/2 inhibitor) and assess the impact of this intervention on survival and IEC tumor growth...
  36. Targeting BRAF and MEK in tumors with BRAF and RAS mutations.
    David B Solit; Fiscal Year: 2012
    ..tumor cells with activating BRAF(V600E) mutations are selectively sensitive to PD0325901, a selective inhibitor of MEK1/2...
  37. Targeting the Estrogen Pathway for the Prevention and Treatment of LAM
    Jane Yu; Fiscal Year: 2013
    ..Aim 3. To determine whether inhibition of MEK1/2 and ER( leads to a regression of established lung metastasis of ELT3 cells...
    KAVITA YANG SARIN; Fiscal Year: 2011
    ..recent work from our laboratory revealed that ablation of Erk MAPK cascade signaling at the level of both Mek1/2 and Erk1/2 not only blocked Ras/Raf driven neoplastic changes but also resulted in growth inhibition and ..
  39. Physiologic Function of RAS Effectors MEK 1/2 on Epidermal Differentiation
    Todd W Ridky; Fiscal Year: 2011
    ..b>MEK1 null mice are embryonic lethal, precluding establishment of epidermal phenotypes;however, MEK2 null mice are normal...
  40. Reducing dietary copper for the treatment of BRaf mutation-positive melanoma
    CHRISTOPHER COUNTER; Fiscal Year: 2013 components, we note that half of melanomas encode an oncogenic mutant BRafV600E kinase, which phosphorylates Mek1/2 kinases and in turn Erk1/2, thereby activating the MAPK pathway to promote melanoma...
  41. Overcoming Drug-Induced Resistance in BRaf mutated melanoma cells
    Ramin Samadani; Fiscal Year: 2013
    ..New treatments inhibiting BRaf or its direct target MEK1/2 proteins have recently been developed and have shown promising results in clinical trials...
  42. Mechanism of T Cell Resistance against Treg-mediated suppression in asthma
    Rafeul Alam; Fiscal Year: 2010
    ..will examine whether the ERK1/2 signaling module establishes a self-sustaining mechanism through the induction of a MEK1-dependent positive feedback loop and inhibition of a MKP3-dependent negative feedback loop...
  43. Molecular mechanisms of signaling co-ordination in innate lymphocytes
    Subramaniam Malarkannan; Fiscal Year: 2013
    ..forms a novel signalosome around the perinuclear region to regulate ERK1/2 activation via Rac1->Pak->Raf->MEK1/2 pathway...
  44. Mechanisms of MEK/ERK growth arrest signaling
    Jong In Park; Fiscal Year: 2013
    ..tissue specimens;(ii) determine whether mortalin regulates the Raf/MEK/ERK pathway by differentially sequestering MEK1 or MEK2;and (iii) determine molecular mechanisms underlying the non-catalytic ERK functions...
  45. Signaling Mechanisms Regulation Muscle Protein Turnover
    S Price; Fiscal Year: 2005
    ..Next, we will determine if regulating SGK or MEK1 (the upstream activator of ERK1/2) will change protein degradation and expression of ubiquitin-proteasome pathway ..
  46. MDA-7/IL-24 and free radicals in renal cancer therapy
    Paul Dent; Fiscal Year: 2009
    ..Specific aim 2 will determine the mechanisms by which combined treatment of RCCs with PI3 kinase and MEK1/2 inhibitors enhance cell killing by purified MDA-7 protein...
    Bali Pulendran; Fiscal Year: 2006
    ..At low concentrations, it cleaves components of the MAP-kinase pathway (MKK1,2 & 3), thereby rendering macrophages anergic to further stimulation by LPS...
  48. Gene Structure and Transciptional Regulation
    RICHARD FIRTEL; Fiscal Year: 2007
    ..SMEK1, an evolutionarily-conserved, second-site suppressor of MEK1 that was identified in my lab in regulating the MEK 1/ERK1 pathway and chemotaxis...
  49. Developmental Retinal Neovascularization
    Lois Smith; Fiscal Year: 2007
    ..We will define in EC and in the new mouse model the selectivity of MEK1 inhibition for blocking vessel proliferation over survival...
  50. 17 alpha-Hydroxylase Expression in Human Ovarian Cells
    Jan M McAllister; Fiscal Year: 2010
    ..CYP17) gene expression in PCOS theca cells results from a combined reduction in the activation state of the MEK1/ERK pathway and a stimulation in the activation state of the MKK3 pathway...
  51. Caveolin-1, Caveolae and Placental Angiogenesis
    DongBao Chen; Fiscal Year: 2007
    ..e., Ras-Raf-MEK1-ERK2/1 and PI3K/Akt signaling modules, in the caveolae of endothelial cells (EC), thereby modulating VEGF ..
  52. Regulation of type IV collagenase expression
    Douglas Boyd; Fiscal Year: 2007
    ..Similarly, the MEK1 inhibitor PD098059 represses MMP-9 expression and in Specific Aim # 3 we will determine if the transcriptional ..
  53. Fibronectin Polymerization: Effects on Cell Signaling
    PAULA MC KEOWN LONGO; Fiscal Year: 2009
    ..inhibitors, and dominant/negative adenoviral constructs will be used to define the role of the Ras/Raf1 MEK1 pathway in the activation of ERK by LPA...
    Alan Wolfman; Fiscal Year: 2003
    ..Raf-1, MEK1 and c-N-Ras are all found in a purified mitochondrial preparation, supporting our hypothesis that c-N-Ras plays a ..
    Marita Thompson; Fiscal Year: 2004
    ..Response to LPS will be determined by evaluating the LPS signal transduction pathway via MEK1, ERK2 and NF-kappaB...
    Vivek Malhotra; Fiscal Year: 2007
    ..We have proposed the existence of a Golgi membrane specific cell-cycle checkpoint. We have found that kinases MEK1 and Polo like kinase (Plk); and Golgi associated proteins GRASP55 and GRASP65 are required for Golgi fragmentation...
    Gerald Siu; Fiscal Year: 2002
    ..has determined that the translocation of SAF to the nucleus in DP T cells is mediated by signaling from the Mek1 branch of the MAPK pathway, which has been previously shown to convey positive selection signals in developing ..
    Michael Reidy; Fiscal Year: 2001
    ..Activation of this pathway will be inhibited in vivo with a topically applied MEK1 inhibitor and the effect on SMC replication quantitated...
    WILLIAM JARVIS; Fiscal Year: 2005
    ..sustained generation of the cytoprotective lipid messenger diglyceride, and consequent activation of the Raf-1->MEK1->ERK1->ERK2 sequence...
  60. Regulation of angiotensin-induced PAI-1 expression
    EDWARD FEENER; Fiscal Year: 2006
    ..These results demonstrate a novel mechanism for MEKK-1/MEK1,2 activation of the PAI-1 promoter that is dependent on the cooperative effects of adjacent Sp1 and AP-1 elements...
  61. Non-Peptides Inhibitors of Anthrax Lethal Factor
    DARRYL RIDEOUT; Fiscal Year: 2003
    ..extracted 3D-pharmacophore information from the computationally modeled LF substrate MAPKK1 during Phase I...
  62. Mechanisms of Eosinophil Adhesion
    Xiangdong Zhu; Fiscal Year: 2006
    ..on eosinophil adhesion using selective MAPK pathway inhibitors and dominant negative and active mutants of MEK1. Using dominant negative Ras and ERK pathway inhibitors, the causal relationship between Ras, ERK and cPLA 2 ..