MEK1

Summary

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

Top Publications

  1. 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
  2. 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
  3. ncbi Selective inhibitors of MEK1/ERK44/42 and p38 mitogen-activated protein kinases potentiate apoptosis induction by sulindac sulfide in human colon carcinoma cells
    Yunjie Sun
    Division of Gastroenterology Hepatology, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA
    Mol Cancer Ther 4:51-9. 2005
  4. 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
  5. 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
  6. 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
  7. 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
  8. ncbi 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
  9. ncbi 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
  10. 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

Research Grants

  1. Role of bacterial virulence proteins in plant cell death
    Gregory Martin; Fiscal Year: 2007
  2. Role of bacterial virulence proteins in plant cell death
    Gregory Martin; Fiscal Year: 2009
  3. INSULIN-REGULATED MAP KINASE PATHWAYS
    Melanie Cobb; Fiscal Year: 2006
  4. INSULIN-REGULATED MAP KINASE PATHWAYS
    Melanie Cobb; Fiscal Year: 2000
  5. REGULATION OF APOPTOSIS BY CELLULAR RAS ISOFORMS
    Alan Wolfman; Fiscal Year: 2003
  6. ANALYSIS OF MEIOTIC CHROMOSOME SYNAPSIS IN YEAST
    Nancy M Hollingsworth; Fiscal Year: 2010
  7. ANALYSIS OF MEIOTIC CHROMOSOME SYNAPSIS IN YEAST
    NANCY HOLLINGSWORTH; Fiscal Year: 2009
  8. ANALYSIS OF MEIOTIC CHROMOSOME SYNAPSIS IN YEAST
    NANCY HOLLINGSWORTH; Fiscal Year: 1999
  9. ANALYSIS OF MEIOTIC CHROMOSOME SYNAPSIS IN YEAST
    NANCY HOLLINGSWORTH; Fiscal Year: 2003
  10. SIGNALING PATHWAYS REGULATING EPITHELIAL CELL SURVIVAL
    Paul Dent; Fiscal Year: 2010

Detail Information

Publications169 found, 100 shown here

  1. 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...
  2. 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...
  3. ncbi Selective inhibitors of MEK1/ERK44/42 and p38 mitogen-activated protein kinases potentiate apoptosis induction by sulindac sulfide in human colon carcinoma cells
    Yunjie Sun
    Division of Gastroenterology Hepatology, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA
    Mol Cancer Ther 4:51-9. 2005
    ..Selective inhibitors of these MAPKs potentiate apoptosis induction by this NSAID, suggesting a novel strategy for the prevention or treatment of colorectal cancer...
  4. 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...
  5. 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...
  6. 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...
  7. 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...
  8. ncbi 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...
  9. ncbi 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 ..
  10. 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...
  11. ncbi 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...
  12. ncbi 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 ..
  13. 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...
  14. 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).
  15. 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...
  16. ncbi 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...
  17. ncbi 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 ..
  18. 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...
  19. 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,..
  20. 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...
  21. ncbi Activation of MEK1/ERK1/2/iNOS/sGC/PKG pathway associated with peroxynitrite formation contributes to hypotension and vascular hyporeactivity in endotoxemic rats
    Belma Korkmaz
    Department of Pharmacology, Faculty of Pharmacy, Mersin University, Mersin, Turkey
    Nitric Oxide 24:160-72. 2011
    ..increase in protein expression and activity of the enzymes involved in mitogen-activated protein kinase kinase 1 (MEK1)/extracellular signal-regulated kinase 1/2 (ERK1/2)/iNOS/soluble guanylyl cyclase (sGC)/protein kinase G (PKG) ..
  22. ncbi 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)...
  23. ncbi Diurnal variation in p42/44 mitogen-activated protein kinase in the rat pineal gland
    A K Ho
    Department of Physiology, Faculty of Medicine, 7 26 Medical Sciences Building, University of Alberta, Edmonton, Alta, Canada T6G 2H7
    Mol Cell Endocrinol 208:23-30. 2003
    ..regimen with 12h of darkness, there was a two- to four-fold increase in phosphorylated levels of MAPK kinase 1/2 (MEK1/2) and p42/44(MAPK) 2h after onset of darkness, an increase that was sustained for 8h...
  24. ncbi 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...
  25. ncbi 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...
  26. ncbi 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)...
  27. ncbi 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]...
  28. 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)...
  29. 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...
  30. 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
    ..is 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...
  31. 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...
  32. ncbi 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...
  33. 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...
  34. 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...
  35. 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...
  36. ncbi 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 ..
  37. ncbi 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...
  38. ncbi 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 ..
  39. 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)...
  40. 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 ..
  41. 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...
  42. ncbi 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...
  43. 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...
  44. 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...
  45. 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 ..
  46. 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...
  47. ncbi 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 ..
  48. ncbi 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
    ..It declined to baseline level at 30 min. The ET-1-induced activation of ERK1/2 was completely abolished by MEK1/2 inhibitors U0126 and SL327, and partially inhibited by the MEK1 inhibitor PD98059...
  49. ncbi 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...
  50. 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...
  51. 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...
  52. 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)...
  53. ncbi Association of MEK1 with p21ras.GMPPNP is dependent on B-Raf
    S A Moodie
    Department of Cell Biology, Cleveland Clinic Foundation, Ohio 44195
    Mol Cell Biol 14:7153-62. 1994
    ..We have extended those observations to show that MEK1 is the MEK activity previously described to associate with immobilized p21ras.GMPPNP...
  54. 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...
  55. ncbi 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...
  56. 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...
  57. ncbi 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 ..
  58. 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...
  59. ncbi 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...
  60. 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...
  61. 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...
  62. ncbi 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...
  63. 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 ..
  64. ncbi 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 ..
  65. 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...
  66. ncbi 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...
  67. 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
    ....
  68. 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...
  69. ncbi 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...
  70. ncbi Kinase suppressor of Ras forms a multiprotein signaling complex and modulates MEK localization
    S Stewart
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109 0606, USA
    Mol Cell Biol 19:5523-34. 1999
    ..multimolecular signaling complex in human embryonic kidney 293T cells composed of HSP90, HSP70, HSP68, p50(CDC37), MEK1, MEK2, 14-3-3, and several other, unidentified proteins...
  71. ncbi Exome sequencing identifies recurrent somatic MAP2K1 and MAP2K2 mutations in melanoma
    Sergey I Nikolaev
    Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland
    Nat Genet 44:133-9. 2012
    ..Two melanomas with non-canonical BRAF mutations harbored gain-of-function MAP2K1 and MAP2K2 (MEK1 and MEK2, respectively) mutations, resulting in constitutive ERK phosphorylation and higher resistance to MEK ..
  72. ncbi MEK1/2 inhibitor selumetinib (AZD6244) inhibits growth of ovarian clear cell carcinoma in a PEA-15-dependent manner in a mouse xenograft model
    Chandra Bartholomeusz
    Breast Cancer Translational Research Laboratory, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Mol Cancer Ther 11:360-9. 2012
    ..PEA-15, a 15-kDa phosphoprotein, can sequester ERK in the cytoplasm. MEK1/2 plays a central role in integrating mitogenic signals into the ERK pathway...
  73. ncbi Enhancement of mitomycin C-induced cytotoxicity by curcumin results from down-regulation of MKK1/2-ERK1/2-mediated thymidine phosphorylase expression
    Shao Hsing Weng
    Molecular Oncology Laboratory, Department of Biochemical Science and Technology, National Chiayi University, Chiayi, Taiwan
    Basic Clin Pharmacol Toxicol 110:298-306. 2012
    ..Exposure of human NSCLC cell lines H1975 and H1650 to curcumin decreased MMC-elicited phosphorylated MKK1/2-ERK1/2 protein levels...
  74. ncbi Combinations of BRAF, MEK, and PI3K/mTOR inhibitors overcome acquired resistance to the BRAF inhibitor GSK2118436 dabrafenib, mediated by NRAS or MEK mutations
    James G Greger
    Oncology R and D Translational Research, GlaxoSmithKline, Collegeville, Pennsylvania, USA
    Mol Cancer Ther 11:909-20. 2012
    ..Genetic characterization of these clones identified an in-frame deletion in MEK1 (MEK1(K59del)) or NRAS mutation (NRAS(Q61K) and/or NRAS(A146T)) with and without MEK1(P387S) in the BRAF(V600E) ..
  75. ncbi Red1p, a MEK1-dependent phosphoprotein that physically interacts with Hop1p during meiosis in yeast
    T de los Santos
    Department of Biochemistry and Cell Biology, Institute for Cell and Developmental Biology, SUNY Stony Brook, Stony Brook, New York 11794 5215, USA
    J Biol Chem 274:1783-90. 1999
    ..cerevisiae, HOP1 and RED1, is critical for proper assembly and function of the SC. A third meiosis-specific gene, MEK1, which encodes a putative serine/threonine protein kinase, is also important for proper AE function, suggesting ..
  76. ncbi Immunolocalization of the mitogen-activated protein kinases p42MAPK and JNK1, and their regulatory kinases MEK1 and MEK4, in adult rat central nervous system
    D G Flood
    Department of Molecular Biology, Cephalon, Inc, West Chester, Pennsylvania 19380, USA
    J Comp Neurol 398:373-92. 1998
    ..compared the distribution of p42 mitogen-activated protein kinase (p42MAPK) and its activator MAPK or ERK kinase (MEK1; involved in transduction of growth and differentiation signals), with c-Jun N-terminal kinase (JNK1) and its ..
  77. ncbi Isolation of ATMEKK1 (a MAP kinase kinase kinase)-interacting proteins and analysis of a MAP kinase cascade in Arabidopsis
    K Ichimura
    Laboratory of Plant Molecular Biology, Institute of Physical and Chemical Research RIKEN, Tsukuba Life Science Center, Japan
    Biochem Biophys Res Commun 253:532-43. 1998
    ..ATMKK2 has high sequence similarity with MEK1 (a MAPKK) in Arabidopsis...
  78. ncbi A novel tandem affinity purification strategy for the efficient isolation and characterisation of native protein complexes
    Christian Johannes Gloeckner
    Institute of Human Genetics, GSF National Research Center for Environment and Health, Neuherberg, Germany
    Proteomics 7:4228-34. 2007
    ..is demonstrated by the purification of Raf associated protein complexes from HEK293 cells and subsequent analysis of their protein interaction network by dissection of interaction patterns from the Raf binding partners MEK1 and 14-3-3.
  79. ncbi The Arabidopsis MAP kinase kinase MKK1 participates in defence responses to the bacterial elicitor flagellin
    Tamas Meszaros
    School of Biological Sciences, Royal Holloway University of London, Egham TW20 0EX, UK
    Plant J 48:485-98. 2006
    ..The endogenous Arabidopsis MAP kinase kinase MKK1 is activated in cells treated with flg22, phosphorylates the MAPK MPK4 in vitro, and activates it in vivo in ..
  80. ncbi Interaction with MEK causes nuclear export and downregulation of peroxisome proliferator-activated receptor gamma
    Elke Burgermeister
    Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel
    Mol Cell Biol 27:803-17. 2007
    ..This interaction is facilitated by MEKs' phosphorylation and is mediated by the basic D domain of MEK1 and the AF2 domain of PPARgamma...
  81. ncbi ERK1/2-driven and MKP-mediated inhibition of EGF-induced ERK5 signaling in human proximal tubular cells
    Rita Sarközi
    Clinical Division of Nephrology, Department of Internal Medicine, Medical University of Innsbruck, Innsbruck, Austria
    J Cell Physiol 211:88-100. 2007
    The MEK1-ERK1/2 signaling pathway has been implicated in the regulation of renal epithelial cell proliferation, epithelial-to-mesenchymal transition and the induction of an invasive cell phenotype...
  82. 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...
  83. ncbi Ribosomal subunit kinase-2 is required for growth factor-stimulated transcription of the c-Fos gene
    J C Bruning
    Klinik II und Poliklinik für Innere Medizin and Center of Molecular Medicine der Universität zu Köln, Joseph Stelzmann Strasse 9, 50931 Cologne, Germany
    Proc Natl Acad Sci U S A 97:2462-7. 2000
    ....
  84. ncbi Identification of the sites in MAP kinase kinase-1 phosphorylated by p74raf-1
    D R Alessi
    Department of Biochemistry, University of Dundee, Scotland
    EMBO J 13:1610-9. 1994
    ..To understand the mechanism of activation of MAPKK, we have identified Ser217 and Ser221 of MAPKK1 as the sites phosphorylated by p74raf-1...
  85. ncbi Germline mutations of MEK in cardio-facio-cutaneous syndrome are sensitive to MEK and RAF inhibition: implications for therapeutic options
    Thanaset Senawong
    Department of Pathology, School of Medicine, University of California, San Francisco, CA 94143 0128, USA
    Hum Mol Genet 17:419-30. 2008
    ..We recently reported missense germline mutations in the genes MEK1 and MEK2 in patients with CFC...
  86. ncbi Retrophosphorylation of Mkk1 and Mkk2 MAPKKs by the Slt2 MAPK in the yeast cell integrity pathway
    Maria Jimenez-Sanchez
    Departamento de Microbiologia II, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain
    J Biol Chem 282:31174-85. 2007
    ..MAPK module lies downstream of the Rho1 small GTPase and protein kinase C Pkc1 and consists of MAPKKK Bck1, MAPKKs Mkk1 and Mkk2, and the Slt2 MAPK...
  87. ncbi Premature senescence involving p53 and p16 is activated in response to constitutive MEK/MAPK mitogenic signaling
    A W Lin
    Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA
    Genes Dev 12:3008-19. 1998
    ..Consequently, constitutive MAPK signaling activates p53 and p16 as tumor suppressors...
  88. ncbi ERK-dependent threonine phosphorylation of EGF receptor modulates receptor downregulation and signaling
    Xin Li
    Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294 0012, United States
    Cell Signal 20:2145-55. 2008
    ..Additionally, EGFR undergoes MEK1-dependent ERK consensus site phosphorylation in response to EGF or cytokines such as growth hormone (GH) and ..
  89. ncbi Genetic interactions between HOP1, RED1 and MEK1 suggest that MEK1 regulates assembly of axial element components during meiosis in the yeast Saccharomyces cerevisiae
    N M Hollingsworth
    Department of Biochemistry and Cell Biology, State University of New York at Stony Brook 11794 5215, USA
    Genetics 147:33-42. 1997
    ..Genetic and cytological data suggest that three meiosis-specific genes, HOP1, RED1 and MEK1, are involved in axial element formation in the yeast Saccharomyces cerevisiae...
  90. ncbi Aldosterone-induced mesangial cell proliferation is mediated by EGF receptor transactivation
    Songming Huang
    Department of Nephrology, Nanjing Children s Hospital, Nanjing Medical Univ, Nanjing, China
    Am J Physiol Renal Physiol 296:F1323-33. 2009
    ..Aldo increased Ki-RasA and Ki-RasA:GTP levels, and sequentially phosphorylated c-Raf, MAPK kinase (MEK1/2), and ERK1/2...
  91. ncbi Halogen bonding at the active sites of human cathepsin L and MEK1 kinase: efficient interactions in different environments
    Leo A Hardegger
    Laboratorium fur Organische Chemie, ETH Zurich, Wolfgang Pauli Strasse 10, HCI, 8093 Zurich, Switzerland
    ChemMedChem 6:2048-54. 2011
    In two series of small-molecule ligands, one inhibiting human cathepsin L (hcatL) and the other MEK1 kinase, biological affinities were found to strongly increase when an aryl ring of the inhibitors is substituted with the larger ..
  92. ncbi A correction to the research article titled: "Amplification of the driving oncogene, KRAS or BRAF, underpins acquired resistance to MEK1/2 inhibitors in colorectal cancer cells" by A. S. Little, K. Balmanno, M. J. Sale, S. Newman, J. R. Dry, M.
    Annette S Little
    Laboratory of Molecular Signalling, Babraham Institute, Cambridge, UK
    Sci Signal 4:er2. 2011
    ..We modeled acquired resistance to the MEK1/2 (mitogen-activated or extracellular signal–regulated protein kinase kinases 1 and 2) inhibitor selumetinib (..
  93. ncbi Two mitogen-activated protein kinase kinases, MKK1 and MEK2, are involved in wounding- and specialist lepidopteran herbivore Manduca sexta-induced responses in Nicotiana attenuata
    Maria Heinrich
    Department of Molecular Ecology, Max Planck Institute for Chemical Ecology, Hans Knöll Str 8, D 07745 Jena, Germany
    J Exp Bot 62:4355-65. 2011
    ..Ectopic overexpression studies in N. benthamiana and N. tabacum suggested that two MAPKKs, MKK1 and MEK2, may activate SIPK and WIPK. The homologues of MKK1 and MEK2 were cloned in N...
  94. ncbi MEK1 gene mutation in Japanese lung adenocarcinoma patients
    Hidefumi Sasaki
    Department of Surgery II, Nagoya City University Medical School, Nagoya 467 8601, Japan hisasaki med nagoya cu ac jp
    Mol Med Report 2:153-5. 2009
    ..identify potential somatic mutations in genes of the epidermal growth factor receptor (EGFR) signaling pathway, the MEK1 gene mutation at exon 2 was identified...
  95. ncbi Identification of predictive markers of response to the MEK1/2 inhibitor selumetinib (AZD6244) in K-ras-mutated colorectal cancer
    John J Tentler
    Division of Medical Oncology, University of Colorado Denver Anschutz Medical Campus, Aurora, Colorado 80045, USA
    Mol Cancer Ther 9:3351-62. 2010
    ..The aim of this study was to develop and characterize predictive biomarkers of response to the MEK1/2 inhibitor AZD6244 in CRC in order to maximize the clinical utility of this agent...
  96. ncbi MAP kinase binds to the NH2-terminal activation domain of c-Myc
    S Gupta
    Department of Biochemistry and Molecular Biology, University of Massachusetts Medical School, Worcester 01605
    FEBS Lett 353:281-5. 1994
    ..However, the c-Myc/MAP kinase complex is disrupted by ATP. Together, these observations indicate that substrate binding interactions contribute to the specificity of phosphorylation by MAP kinases...
  97. ncbi MicroRNA-34a inhibits cell proliferation by repressing mitogen-activated protein kinase kinase 1 during megakaryocytic differentiation of K562 cells
    Atsuhiko Ichimura
    Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Sciences, Kyoto University, 46 29 Yoshida Shimoadachi cho Sakyo ku, Kyoto 606 8501, Japan
    Mol Pharmacol 77:1016-24. 2010
    ..Reporter gene assays identified mitogen-activated protein kinase kinase 1 (MEK1) as a direct target of miR-34a and c-fos as a direct target of miR-221/222...
  98. ncbi Cerebral ischemia induces microvascular pro-inflammatory cytokine expression via the MEK/ERK pathway
    Aida Maddahi
    Department of Internal Medicine, Institute of Clinical Sciences, Lund University, Sweden
    J Neuroinflammation 7:14. 2010
    ..In this study, we hypothesised that inhibition of the cerebrovascular inflammatory reaction with a specific MEK1/2 inhibitor (U0126) to block transcription or a combined receptor blockade would reduce infarct size and improve ..
  99. ncbi Distinct effects of knocking down MEK1 and MEK2 on replication of herpes simplex virus type 2
    Hao Zhang
    Department of Microbiology, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, PR China
    Virus Res 150:22-7. 2010
    ..b>MEK1 and MEK2 are two isoforms of the kinase operating immediately upstream of ERK, and connecting Raf and ERK by ..
  100. ncbi Role of the nuclear receptors HNF4 alpha, PPAR alpha, and LXRs in the TNF alpha-mediated inhibition of human apolipoprotein A-I gene expression in HepG2 cells
    Denis A Mogilenko
    Department of Biochemistry, Institute of Experimental Medicine, Russian Academy of Medical Sciences, 197376 St Petersburg, Russia
    Biochemistry 48:11950-60. 2009
    ..rate of secretion of apoA-I protein by HepG2 cells, and this effect depends on JNK and p38, but not on NFkappaB and MEK1/2 signaling pathways...
  101. ncbi Meiotic cells monitor the status of the interhomolog recombination complex
    L Xu
    Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA
    Genes Dev 11:106-18. 1997
    ..We report here the effects of mutations in two other (meiosis-specific) genes, RED1 and MEK1/MRE4, that encode a chromosome structure component and a protein kinase, respectively...

Research Grants63

  1. Role of bacterial virulence proteins in plant cell death
    Gregory Martin; Fiscal Year: 2007
    ..Possible host targets of AvrPtoB anti-PCD activity, including MEK1, a MAPKK, have been identified...
  2. Role of bacterial virulence proteins in plant cell death
    Gregory Martin; Fiscal Year: 2009
    ..Possible host targets of AvrPtoB anti-PCD activity, including MEK1, a MAPKK, have been identified...
  3. INSULIN-REGULATED MAP KINASE PATHWAYS
    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...
  4. INSULIN-REGULATED MAP KINASE PATHWAYS
    Melanie Cobb; Fiscal Year: 2000
    ..The module consists of Raf isoforms which activate the MAPERK kinases (MEK), MEK1 and MEK2, which in turn activate ERK1 and ERK2...
  5. REGULATION OF APOPTOSIS BY CELLULAR RAS ISOFORMS
    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 ..
  6. ANALYSIS OF MEIOTIC CHROMOSOME SYNAPSIS IN YEAST
    Nancy M Hollingsworth; Fiscal Year: 2010
    ..This suppression is mediated by Mek1, a meiosis-specific serine/threonine kinase...
  7. ANALYSIS OF MEIOTIC CHROMOSOME SYNAPSIS IN YEAST
    NANCY HOLLINGSWORTH; Fiscal Year: 2009
    ..This suppression is mediated by Mek1, a meiosis-specific serine/threonine kinase...
  8. ANALYSIS OF MEIOTIC CHROMOSOME SYNAPSIS IN YEAST
    NANCY HOLLINGSWORTH; Fiscal Year: 1999
    ..copy suppression and synthetic spore lethality, will be performed using specially selected alleles of HOP1, RED1, MEK1 and HCS1-7...
  9. ANALYSIS OF MEIOTIC CHROMOSOME SYNAPSIS IN YEAST
    NANCY HOLLINGSWORTH; Fiscal Year: 2003
    ..Three key meiosis-specific components of yeast AEs are HOP1, RED1 and MEK1. Genetic experiments suggest that a balance between Hop1p/Red1p complexes and Red1p homo-oligomers is important for ..
  10. SIGNALING PATHWAYS REGULATING EPITHELIAL CELL SURVIVAL
    Paul Dent; Fiscal Year: 2010
    ..We also have published data demonstrating that geldanamycins (17AAG, 17DMAG) + MEK1/2 inhibitors synergize to kill liver and pancreatic tumor cells via CD95 activation...
  11. Linkage of Lung Inflammation to 8-oxoguanine and OGG1
    ISTVAN STEVEN BOLDOGH; Fiscal Year: 2010
    ..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...
  12. 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...
  13. Developmental Retinal Neovascularization
    Lois Smith; Fiscal Year: 2003
    ..We will define in EC and in the new mouse model the selectivity of MEK1 inhibition for blocking vessel proliferation over survival...
  14. Developmental Retinal Neovascularization
    Lois Smith; Fiscal Year: 2006
    ..We will define in EC and in the new mouse model the selectivity of MEK1 inhibition for blocking vessel proliferation over survival...
  15. PSYCHOPHYSIOLOGY OF IRRITABLE BOWEL SYNDROME
    William Whitehead; Fiscal Year: 2009
    ..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. ..
  16. PSYCHOPHYSIOLOGY OF IRRITABLE BOWEL SYNDROME
    William E Whitehead; Fiscal Year: 2010
    ..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. PSYCHOPHYSIOLOGY OF IRRITABLE BOWEL SYNDROME
    William Whitehead; Fiscal Year: 2009
    ..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. ..
  18. Regulation of type IV collagenase expression
    Douglas Boyd; Fiscal Year: 2006
    ..Similarly, the MEK1 inhibitor PD098059 represses MMP-9 expression and in Specific Aim 3 we will determine if the transcriptional ..
  19. Regulation of type IV collagenase expression
    Douglas Boyd; Fiscal Year: 2003
    ..Similarly, the MEK1 inhibitor PD098059 represses MMP-9 expression and in Specific Aim 3 we will determine if the transcriptional ..
  20. 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 ..
  21. MDA-7/IL-24 and free radicals in renal cancer therapy
    Paul Dent; Fiscal Year: 2007
    ..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...
  22. Oxidative Stress in Cr(VI)-induced Carcinogenesis
    Xianglin Shi; Fiscal Year: 2010
    ..We will use a dominant negative mutant MEK1/2, a dominant negative mutant ERK2, or a dominant negative mutant c-jun (TAM67), respectively, to investigate the ..
  23. Oxidative Stress in Cr(VI)-induced Carcinogenesis
    Xianglin Shi; Fiscal Year: 2007
    ..We will use a dominant negative mutant MEK1/2, a dominant negative mutant ERK2, or a dominant negative mutant c-jun (TAM67), respectively, to investigate the ..
  24. 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...
  25. ANTHRAX TOXIN, DENDRITIC CELLS AND ADAPTIVE IMMUNITY
    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...
  26. 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...
  27. Tyrosine Phosphorylation and Growth Hormone Signalling
    STUART FRANK; Fiscal Year: 2004
    ..phosphorylation of Gab 1, an adaptor protein important in growth factor-induced MAPK signaling; 4) GH, via a MEK1/MAPK-dependent pathway, inhibits activation of ErbB-2, an epidermal growth factor (EGF) receptor family member, and ..