map kinase kinase kinase 1

Summary

Summary: A 195-kDa MAP kinase kinase kinase with broad specificity for MAP KINASE KINASES. It is found localized in the CYTOSKELETON and can activate a variety of MAP kinase-dependent pathways.

Top Publications

  1. pmc Genome-wide association study identifies novel breast cancer susceptibility loci
    Douglas F Easton
    CR UK Genetic Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK
    Nature 447:1087-93. 2007
  2. pmc Replication of five GWAS-identified loci and breast cancer risk among Hispanic and non-Hispanic white women living in the Southwestern United States
    Martha L Slattery
    University of Utah, Salt Lake City, UT, 84108, USA
    Breast Cancer Res Treat 129:531-9. 2011
  3. ncbi The MAPKKK Mekk1 regulates the expression of Turandot stress genes in response to septic injury in Drosophila
    Sylvain Brun
    Centre de Genetique Moleculaire, CNRS, 91198 Gif sur Yvette, France
    Genes Cells 11:397-407. 2006
  4. ncbi Mitogen-activated protein kinase pathways
    M J Robinson
    University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235 904, 1 USA
    Curr Opin Cell Biol 9:180-6. 1997
  5. ncbi Induction of cyclooxygenase-2 by the activated MEKK1 --> SEK1/MKK4 --> p38 mitogen-activated protein kinase pathway
    Z Guan
    Department of Molecular Biology and Pharmacology and Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 273:12901-8. 1998
  6. pmc Hormone-dependent effects of FGFR2 and MAP3K1 in breast cancer susceptibility in a population-based sample of post-menopausal African-American and European-American women
    Timothy R Rebbeck
    Abramson Cancer Center, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Carcinogenesis 30:269-74. 2009
  7. pmc Mutations in MAP3K1 cause 46,XY disorders of sex development and implicate a common signal transduction pathway in human testis determination
    Alexander Pearlman
    New York University School of Medicine, New York, 10016, USA
    Am J Hum Genet 87:898-904. 2010
  8. ncbi Inheritance of stress-induced, ATF-2-dependent epigenetic change
    Ki Hyeon Seong
    Laboratory of Molecular Genetics, RIKEN Tsukuba Institute, 3 1 1 Koyadai, Tsukuba, Ibaraki 305 0074, Japan
    Cell 145:1049-61. 2011
  9. ncbi Stimulation of p300-mediated transcription by the kinase MEKK1
    R H See
    Department of Pathology, Harvard Medical School and Department of Radiation Biology, Harvard School of Public Health, Boston, Massachusetts 02115
    J Biol Chem 276:16310-7. 2001
  10. ncbi RhoA binds to the amino terminus of MEKK1 and regulates its kinase activity
    Ewen D Gallagher
    Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390 9041, USA
    J Biol Chem 279:1872-7. 2004

Research Grants

  1. MOLECULAR MEDIATORS OF DIABETIC RENAL HYPERTROPHY
    John Kyriakis; Fiscal Year: 2002
  2. CELL GROWTH REGULATION VIA THE MEKK/SAPK CASCADE
    Dennis Templeton; Fiscal Year: 2003
  3. NIH--EGF/NEU RECEPTOR SIGNAL TRANSDUCTION
    Gary Johnson; Fiscal Year: 2001
  4. MEKK2/3-MEK5 Interaction/Activation/ERK5 Pathway(RMI)
    BRUCE CUEVAS; Fiscal Year: 2005
  5. Nutritional Regulation of Fetal Liver Development
    PHILIP GRUPPUSO; Fiscal Year: 2008
  6. DIET AND SOMATIC MUTATIONS IN COLON CANCER
    MARTHA OR MARTY SLATTERY; Fiscal Year: 2007
  7. Signaling Mechanisms of TCDD-induced AHR Activation
    Ying Xia; Fiscal Year: 2007
  8. Role of Km23 in Ovarian Cancer
    KATHLEEN MULDER; Fiscal Year: 2007
  9. Cyclic GMP Phosphodiesterase in Signaling
    Hsien Yu Wang; Fiscal Year: 2007
  10. Prevention of neointimal thickening by Mst1
    Junichi Sadoshima; Fiscal Year: 2006

Detail Information

Publications175 found, 100 shown here

  1. pmc Genome-wide association study identifies novel breast cancer susceptibility loci
    Douglas F Easton
    CR UK Genetic Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK
    Nature 447:1087-93. 2007
    ..05 level compared with an estimated 1,343 that would be expected by chance, indicating that many additional common susceptibility alleles may be identifiable by this approach...
  2. pmc Replication of five GWAS-identified loci and breast cancer risk among Hispanic and non-Hispanic white women living in the Southwestern United States
    Martha L Slattery
    University of Utah, Salt Lake City, UT, 84108, USA
    Breast Cancer Res Treat 129:531-9. 2011
    ..Our data replicated some of the previously reported GWAS findings. Differences in associations were detected for NHW and Hispanic women by menopausal status and by ER/PR status of tumors...
  3. ncbi The MAPKKK Mekk1 regulates the expression of Turandot stress genes in response to septic injury in Drosophila
    Sylvain Brun
    Centre de Genetique Moleculaire, CNRS, 91198 Gif sur Yvette, France
    Genes Cells 11:397-407. 2006
    ..These results point to a role of Mekk1 in the protection against tissue damage and/or protein degradation and indicate complex interactions between stress and immune pathways in Drosophila...
  4. ncbi Mitogen-activated protein kinase pathways
    M J Robinson
    University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235 904, 1 USA
    Curr Opin Cell Biol 9:180-6. 1997
    ....
  5. ncbi Induction of cyclooxygenase-2 by the activated MEKK1 --> SEK1/MKK4 --> p38 mitogen-activated protein kinase pathway
    Z Guan
    Department of Molecular Biology and Pharmacology and Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 273:12901-8. 1998
    ..Together, this data suggests a potential role for the MEKK1 --> SEK1/MKK4 --> p38 MAPK -->--> Cox-2 cascade linking members of the MAPK pathway with prostaglandin biosynthesis...
  6. pmc Hormone-dependent effects of FGFR2 and MAP3K1 in breast cancer susceptibility in a population-based sample of post-menopausal African-American and European-American women
    Timothy R Rebbeck
    Abramson Cancer Center, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Carcinogenesis 30:269-74. 2009
    ..We further report that these genes confer their effects in HER2- tumors, interact with one another to confer breast cancer susceptibility in AA women and interact with hormone exposures in AA and EA women...
  7. pmc Mutations in MAP3K1 cause 46,XY disorders of sex development and implicate a common signal transduction pathway in human testis determination
    Alexander Pearlman
    New York University School of Medicine, New York, 10016, USA
    Am J Hum Genet 87:898-904. 2010
    ..Thus, mutations in MAP3K1 that result in 46,XY DSD with partial or complete gonadal dysgenesis implicate this pathway in normal human sex determination...
  8. ncbi Inheritance of stress-induced, ATF-2-dependent epigenetic change
    Ki Hyeon Seong
    Laboratory of Molecular Genetics, RIKEN Tsukuba Institute, 3 1 1 Koyadai, Tsukuba, Ibaraki 305 0074, Japan
    Cell 145:1049-61. 2011
    ..The results suggest a mechanism by which the effects of stress are inherited epigenetically via the regulation of a tight chromatin structure...
  9. ncbi Stimulation of p300-mediated transcription by the kinase MEKK1
    R H See
    Department of Pathology, Harvard Medical School and Department of Radiation Biology, Harvard School of Public Health, Boston, Massachusetts 02115
    J Biol Chem 276:16310-7. 2001
    ..Taken together, these results identify MEKK1 as a kinase that is likely to be involved in the regulation of the transactivation potential of p300 and support a role of p300 in MEKK1-induced apoptosis...
  10. ncbi RhoA binds to the amino terminus of MEKK1 and regulates its kinase activity
    Ewen D Gallagher
    Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390 9041, USA
    J Biol Chem 279:1872-7. 2004
    ..In summary, we have characterized a novel point at which Rho GTPases impinge upon the regulation and function of MEKK1...
  11. pmc A role for MEK kinase 1 in TGF-beta/activin-induced epithelium movement and embryonic eyelid closure
    Lin Zhang
    Department of Environmental Health, University of Cincinnati Medical Center, Cincinnati, OH 45267, USA
    EMBO J 22:4443-54. 2003
    ..This study also suggests that the signaling mechanisms that control eyelid closure in mammals and dorsal closure in Drosophila are evolutionarily conserved...
  12. ncbi Genetic interaction and phenotypic analysis of the Arabidopsis MAP kinase pathway mutations mekk1 and mpk4 suggests signaling pathway complexity
    Shih Heng Su
    Genome Center of Wisconsin and Department of Horticulture, University of Wisconsin, Madison, WI 53706, USA
    FEBS Lett 581:3171-7. 2007
    ..Our results suggest that MEKK1 and MPK4 functions are not limited to a single, linear signaling pathway. Instead there appears to be more complexity to the signaling pathways in which these two proteins function...
  13. ncbi Ubiquitylation of MEKK1 inhibits its phosphorylation of MKK1 and MKK4 and activation of the ERK1/2 and JNK pathways
    James A Witowsky
    Department of Pharmacology, University of Colorado Health Sciences Center and University of Colorado Cancer Center, Denver, Colorado 80262, USA
    J Biol Chem 278:1403-6. 2003
    ..MEKK1 ubiquitylation represents a mechanism for inhibiting the ability of a protein kinase to phosphorylate substrates and regulate downstream signaling pathways...
  14. pmc MEK kinases are regulated by EGF and selectively interact with Rac/Cdc42
    G R Fanger
    Division of Basic Sciences, National Jewish Medical and Research Center, Denver, CO 80206, USA
    EMBO J 16:4961-72. 1997
    ..Differential MEKK subcellular distribution and interaction with small GTP-binding proteins provides a mechanism to regulate MAP kinase responses in localized regions of the cell and to different upstream stimuli...
  15. pmc Direct activation of mitogen-activated protein kinase kinase kinase MEKK1 by the Ste20p homologue GCK and the adapter protein TRAF2
    Deborah N Chadee
    Diabetes Research Laboratory, Medical Services, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
    Mol Cell Biol 22:737-49. 2002
    ..These results represent the first activation of MEKK1 in vitro using purified proteins and suggest a mechanism for MEKK1 activation involving induced oligomerization and consequent autophosphorylation mediated by upstream proteins...
  16. pmc Clinical correlates of low-risk variants in FGFR2, TNRC9, MAP3K1, LSP1 and 8q24 in a Dutch cohort of incident breast cancer cases
    Petra E A Huijts
    Department of Clinical Genetics, K5 R, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands
    Breast Cancer Res 9:R78. 2007
    ..Seven SNPs in five genomic loci were recently found to confer a mildly increased risk of breast cancer...
  17. pmc MEKK1 activates both IkappaB kinase alpha and IkappaB kinase beta
    F S Lee
    Department of Molecular and Cellular Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA
    Proc Natl Acad Sci U S A 95:9319-24. 1998
    ..We conclude that IKK-alpha and IKK-beta can mediate the NF-kappaB-inducing activity of MEKK1...
  18. pmc MEKK1 mediates the ubiquitination and degradation of c-Jun in response to osmotic stress
    Yan Xia
    Department of Neuro Oncology, Unit 1002, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
    Mol Cell Biol 27:510-7. 2007
    ..Furthermore, apoptosis induced by osmotic stress was suppressed by overexpression of c-Jun, indicating that the downregulation of c-Jun promotes apoptosis...
  19. ncbi MEKK1 binds HECT E3 ligase Itch by its amino-terminal RING motif to regulate Th2 cytokine gene expression
    Thomas Enzler
    Stanford University School of Medicine, Stanford, CA 94305, USA
    J Immunol 183:3831-8. 2009
    ..MEKK1 phosphorylation on Thr(1381) is observed during Th2 differentiation, but not under Th1 differentiation. Both Itch and the MEKK1 kinase domain are important for Il4 and Il6 cytokine gene expression under Th2 conditions...
  20. pmc Oxidative stress inhibits MEKK1 by site-specific glutathionylation in the ATP-binding domain
    Janet V Cross
    Department of Pathology, University of Virginia Medical School, PO Box 800214, Charlottesville, VA 22908 0214, U S A
    Biochem J 381:675-83. 2004
    ..Our results support a model whereby the redox environment within the cell selectively regulates stress signalling through MEKK1 versus ASK1, and may thereby participate in the induction of apoptosis by oxidative stress...
  21. ncbi Kinase MEKK1 is required for CD40-dependent activation of the kinases Jnk and p38, germinal center formation, B cell proliferation and antibody production
    Ewen Gallagher
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California San Diego, La Jolla, California 92093 0723, USA
    Nat Immunol 8:57-63. 2007
    ..Our data emphasize that MEKK1 is an essential component of signaling cascades needed for thymus-dependent antigen-induced B cell proliferation and antibody production...
  22. pmc MEKK1 is required for flg22-induced MPK4 activation in Arabidopsis plants
    Maria Cristina Suarez-Rodriguez
    Department of Horticulture and Genome Center of Wisconsin, University of Wisconsin, Madison, Wisconsin 53706, USA
    Plant Physiol 143:661-9. 2007
    ..Our results indicate that MEKK1 acts upstream of MPK4 as a negative regulator of pathogen response pathways, a function that may not require MEKK1's full kinase activity...
  23. ncbi The role of c-Jun N-terminal kinase (JNK) in apoptosis induced by ultraviolet C and gamma radiation. Duration of JNK activation may determine cell death and proliferation
    Y R Chen
    Department of Microbiology and Immunology, Baylor College of Medicine, Houston, Texas 77030, USA
    J Biol Chem 271:31929-36. 1996
    ..Our data revealed the requirement of the JNK pathway in radiation-induced apoptosis and implicated the importance of the duration of JNK activation in determining the cell fates...
  24. ncbi Dominant-negative c-Jun promotes neuronal survival by reducing BIM expression and inhibiting mitochondrial cytochrome c release
    J Whitfield
    Eisai London Research Laboratories, Bernard Katz Building, University College London, Gower Street, WC1E 6BT, London, United Kingdom
    Neuron 29:629-43. 2001
    ....
  25. ncbi Binding of JNK/SAPK to MEKK1 is regulated by phosphorylation
    Ewen D Gallagher
    University of Texas Southwestern Medical Center, Department of Pharmacology, Dallas, Texas 75390 9041, USA
    J Biol Chem 277:45785-92. 2002
    ..Phosphorylation of this site inhibits binding of JNK/SAPK to MEKK1. Thus, we propose a mechanism by which the MEKK1-dependent JNK/SAPK pathway is negatively regulated by PAK through phosphorylation of serine 67...
  26. ncbi Inhibitors of mitogen-activated protein kinases differentially regulate eosinophil-activating cytokine release from human airway smooth muscle
    M P Hallsworth
    Department of Respiratory Medicine and Allergy, The Guy's, King's and St. Thomas' School of Medicine, King's College London, Thomas Guy House, Guy's Hospital Campus, London, United Kingdom
    Am J Respir Crit Care Med 164:688-97. 2001
    ....
  27. ncbi Reassessing the MAP3K and MAP4K relationships
    Antony Champion
    Institute of Biology, Leiden University, Clusius Laboratory, Wassenaarseweg 64, 2333 AL Leiden, The Netherlands
    Trends Plant Sci 9:123-9. 2004
  28. ncbi Coregulation of neurite outgrowth and cell survival by amphoterin and S100 proteins through receptor for advanced glycation end products (RAGE) activation
    H J Huttunen
    Programme of Molecular Neurobiology, Institute of Biotechnology, and the Department of Biosciences, University of Helsinki, Helsinki FIN 00014, Finland
    J Biol Chem 275:40096-105. 2000
    ..We suggest that RAGE is a signal-transducing receptor for both trophic and toxic effects of S100B...
  29. ncbi Interfering with cellular signaling pathways enhances sensitization to combined sodium butyrate and GCV treatment in EBV-positive tumor cells
    Yuwen He
    Center of Microbiology, Biochemistry, and Pharmacology, School of Pharmaceutical Science, Sun Yat Sen University, 510080 Guangzhou, China
    Virus Res 135:175-80. 2008
    ..These results suggest that interfering with either the Akt or MEKK1 signaling pathway may be a useful therapeutic strategy to increase the sensitivity of EBV-positive tumor cells to the combination of NaB and GCV...
  30. pmc Induction of c-fos expression through JNK-mediated TCF/Elk-1 phosphorylation
    M Cavigelli
    Department of Pharmacology, School of Medicine, University of California at San Diego, La Jolla 92093 0636, USA
    EMBO J 14:5957-64. 1995
    ....
  31. pmc MEK kinase 1, a substrate for DEVD-directed caspases, is involved in genotoxin-induced apoptosis
    C Widmann
    Division of Basic Sciences, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206, USA
    Mol Cell Biol 18:2416-29. 1998
    ..MEKK1 and caspases are predicted to be part of an amplification loop to increase caspase activity during apoptosis...
  32. pmc A Raf-1 mutant that dissociates MEK/extracellular signal-regulated kinase activation from malignant transformation and differentiation but not proliferation
    Amardeep S Dhillon
    The Beatson Institute for Cancer Research, CR UK Beatson Laboratories, Garscube Estate, Bearsden, Glasgow G61 1BD, Scotland, UK
    Mol Cell Biol 23:1983-93. 2003
    ..The results further suggest that RafS259 mutants inhibit signaling pathways required to promote these biological processes...
  33. pmc MEK kinase activity is not necessary for Raf-1 function
    M Huser
    Department of Biochemistry, MRC Toxicology Unit and Division of Biomedical Services, University of Leicester, University Road, Leicester LE1 7RH, UK
    EMBO J 20:1940-51. 2001
    ..These results strongly argue that MEK kinase activity of Raf-1 is not essential for normal mouse development and that Raf-1 plays a key role in preventing apoptosis...
  34. ncbi c-Jun N-terminal kinase (JNK) positively regulates NFATc2 transactivation through phosphorylation within the N-terminal regulatory domain
    Inmaculada Ortega-Perez
    Centro Nacional de Investigaciones Cardiovasculares CNIC, Ronda de Poniente 5, Tres Cantos, Madrid 28760, Spain
    J Biol Chem 280:20867-78. 2005
    ..Our results indicate that, unlike other NFAT members, the transcriptional activity of NFATc2 is up-regulated by JNK. JNK-mediated phosphorylation of NFATs thus appears to play a differential physiological role among NFAT family members...
  35. pmc MEKK1 transduces activin signals in keratinocytes to induce actin stress fiber formation and migration
    Lin Zhang
    Department of Environmental Health, University of Cincinnati, 123 E Shields St, Cincinnati, OH 45267 0056, USA
    Mol Cell Biol 25:60-5. 2005
    ..Together, these pathways lead to the control of actin cytoskeleton reorganization and epithelial cell migration, contributing to the physiologic and pathological effects of activins on epithelial morphogenesis...
  36. ncbi MEK kinase 1 activity is required for definitive erythropoiesis in the mouse fetal liver
    Barbara Bonnesen
    Institute of Molecular Biology and Physiology, Department of Immunology, University of Copenhagen, Denmark
    Blood 106:3396-404. 2005
    ....
  37. ncbi Role of MEKK1 in cell survival and activation of JNK and ERK pathways defined by targeted gene disruption
    T Yujiri
    Program in Molecular Signal Transduction, Division of Basic Sciences, National Jewish Medical and Research Center, Denver, CO 80206, USA
    Science 282:1911-4. 1998
    ..When activated by specific stresses that alter cell shape and the cytoskeleton, MEKK1 signals to protect cells from apoptosis...
  38. ncbi Apoptosis stimulated by the 91-kDa caspase cleavage MEKK1 fragment requires translocation to soluble cellular compartments
    Thomas K Schlesinger
    Institute of Cellular Biology and Morphology, University of Lausanne, 1005 Lausanne, Switzerland
    J Biol Chem 277:10283-91. 2002
    ....
  39. pmc MEKK1 is essential for DT40 cell apoptosis in response to microtubule disruption
    R Kwan
    Molecular Biology Institute, University of California Los Angeles, Los Angeles, California 90095-1781, USA
    Mol Cell Biol 21:7183-90. 2001
    ....
  40. ncbi The PHD domain of MEKK1 acts as an E3 ubiquitin ligase and mediates ubiquitination and degradation of ERK1/2
    Zhimin Lu
    Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
    Mol Cell 9:945-56. 2002
    ..Therefore, MEKK1 functions not only as an upstream activator of the ERK and JNK through its kinase domain, but also as an E3 ligase through its PHD domain, providing a negative regulatory mechanism for decreasing ERK1/2 activity...
  41. ncbi Activation of stress-activated protein kinase by MEKK1 phosphorylation of its activator SEK1
    M Yan
    Institute of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106
    Nature 372:798-800. 1994
    ..We find that MEKK regulates a new signalling cascade by phosphorylating an SAPK activator, SEK1 which in turn phosphorylates and activates SAPK...
  42. pmc MEK kinase 1 gene disruption alters cell migration and c-Jun NH2-terminal kinase regulation but does not cause a measurable defect in NF-kappa B activation
    T Yujiri
    Third Department of Internal Medicine, Yamaguchi University School of Medicine, Yamaguchi, Japan
    Proc Natl Acad Sci U S A 97:7272-7. 2000
    ..Thus, MEKK1 senses microtubule integrity, contributes to the regulation of fibroblast and epithelial cell migration, and is required for activation of JNK but not NF-kappaB in response to selected stress stimuli...
  43. ncbi Analysis of the role of ubiquitin-interacting motifs in ubiquitin binding and ubiquitylation
    Stephanie L H Miller
    Laboratory of Signal Transduction, NIEHS, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 279:33528-37. 2004
    ..Our results suggest a new model for the ubiquitylation of UIM-containing proteins...
  44. ncbi C-TAK1 regulates Ras signaling by phosphorylating the MAPK scaffold, KSR1
    J Muller
    Regulation of Cell Growth Laboratory, Center for Cancer Research, NCI Frederick, Frederick, MD 21702, USA
    Mol Cell 8:983-93. 2001
    ....
  45. ncbi Role of receptor-interacting protein in tumor necrosis factor-alpha -dependent MEKK1 activation
    J W Kim
    National Creative Research Initiative Center for Cell Death, Graduate School of Biotechnology, Korea University, Seoul 156 701, Korea
    J Biol Chem 276:27064-70. 2001
    ..Taken together, our results suggest that RIP phosphorylates and activates MEKK1 and that RIP is involved in TNF-alpha-induced MEKK1 activation...
  46. ncbi Identification of two essential phosphorylated threonine residues in the catalytic domain of Mekk1. Indirect activation by Pak3 and protein kinase C
    Y L Siow
    Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
    J Biol Chem 272:7586-94. 1997
    ..Although Pak3 and PKC can activate Mekk1 in vivo, this interaction is indirect and independent, since there was no direct phosphorylation of Mekk1 by Pak3 or PKC or of Pak3 by PKC, respectively...
  47. ncbi Activation of the IkappaB alpha kinase complex by MEKK1, a kinase of the JNK pathway
    F S Lee
    Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA
    Cell 88:213-22. 1997
    ..Since the IkappaB alpha kinase complex can be independently activated by ubiquitination or MEKK1-dependent phosphorylation, it may be an integrator of multiple signal transduction pathways leading to the activation of NF-kappaB...
  48. pmc MEK kinase 1 is critically required for c-Jun N-terminal kinase activation by proinflammatory stimuli and growth factor-induced cell migration
    Y Xia
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 97:5243-8. 2000
    ..MEKK1 is also essential for induction of embryonic stem cell migration by serum factors, but is not required for activation of other MAPKs or the IkappaB kinase signaling cascade...
  49. ncbi Tumor necrosis factor-related apoptosis-inducing ligand receptors signal NF-kappaB and JNK activation and apoptosis through distinct pathways
    W H Hu
    National Jewish Medical and Research Center, Division of Basic Immunology, Department of Immunology, Denver, Colorado 80206, USA
    J Biol Chem 274:30603-10. 1999
    ..These findings suggest that TRAIL receptors induce apoptosis, NF-kappaB and JNK activation through distinct signaling pathways, and activation of NF-kappaB is not sufficient for protecting cells from TRAIL-induced apoptosis...
  50. pmc Essential cytoplasmic translocation of a cytokine receptor-assembled signaling complex
    Atsushi Matsuzawa
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0723, USA
    Science 321:663-8. 2008
    ..This two-stage signaling mechanism may apply to other innate immune receptors, accounting for spatial and temporal separation of MAPK and IKK signaling...
  51. ncbi MEK kinase is involved in tumor necrosis factor alpha-induced NF-kappaB activation and degradation of IkappaB-alpha
    M Hirano
    Department of Molecular Biology, Yokohama City University School of Medicine, 3 9 Fuku ura, Kanazawa Ku, Yokohama 236, Japan
    J Biol Chem 271:13234-8. 1996
    ..These results suggest that MEK kinase is a signal mediator involved in TNFalpha-induced NF-kappaB activation and that the activation of NF-kappaB by MEK kinase is regulated through the degradation of IkappaB-alpha...
  52. pmc Cloning of rat MEK kinase 1 cDNA reveals an endogenous membrane-associated 195-kDa protein with a large regulatory domain
    S Xu
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, 75235 9041, USA
    Proc Natl Acad Sci U S A 93:5291-5. 1996
    ....
  53. ncbi Inhibition of the Raf/MEK/ERK pathway up-regulates expression of the coxsackievirus and adenovirus receptor in cancer cells
    Mario Anders
    Cancer Research Institute, University of California, San Francisco 94143, USA
    Cancer Res 63:2088-95. 2003
    ....
  54. ncbi A dominant negative Egr inhibitor blocks nerve growth factor-induced neurite outgrowth by suppressing c-Jun activation: role of an Egr/c-Jun complex
    Yechiel Levkovitz
    Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    J Neurosci 22:3845-54. 2002
    ..Accordingly, our studies indicate that Egr and ZnEgr proteins regulate c-Jun activation via a novel mechanism, protein-protein interaction with c-Jun, rather than via their classical mode of action, binding to the ERE...
  55. ncbi Integration of multiple downstream signals determines the net effect of insulin on MAP kinase vs. PI 3'-kinase activation: potential role of insulin-stimulated H(2)O(2)
    Kalyankar Mahadev
    Department of Medicine, Jefferson Medical College of Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107 6799, USA
    Cell Signal 16:323-31. 2004
    ....
  56. ncbi Inhibition of mitogen-activated protein kinase signaling by chloroquine
    Stephen M Weber
    Department of Microbiology and Evans Memorial Department of Clinical Research and Department of Medicine, Boston University School of Medicine, 650 Albany Street, Boston, MA 02118, USA
    J Immunol 168:5303-9. 2002
    ..Taken together, these data argue that therapeutic concentrations of CQ interfere with ERK activation by a novel mechanism, an effect that could be responsible, at least in part, for the potent anti-inflammatory effects of this drug...
  57. ncbi Multiple signal pathways are involved in the mitogenic effect of 5(S)-HETE in human pancreatic cancer
    Xian Zhong Ding
    Department of Surgery, Northwestern University Medical School, Chicago, IL 60611, USA
    Oncology 65:285-94. 2003
    ....
  58. ncbi Raf-independent and MEKK1-dependent activation of NF-kappaB by hydrogen peroxide in 70Z/3 pre-B lymphocyte tumor cells
    Michael Lee
    Korea Institute of Toxicology, Korea Research Institute of Chemical Technology, P O Box 107, Yusong, Daejeon 305 600, Republic of Korea
    J Cell Biochem 88:545-56. 2003
    ..Therefore, our data suggest that H(2)O(2) regulates the activity of NF-kappaB by MEK1 activation through MEKK1-dependent but Ras/Raf-independent mechanism...
  59. ncbi Role of the amino-terminal domains of MEKKs in the activation of NF kappa B and MAPK pathways and in the regulation of cell proliferation and apoptosis
    Christelle Bonvin
    Institute of Cellular Biology and Morphology, Lausanne University, Lausanne, Switzerland
    Cell Signal 14:123-31. 2002
    ..Our data show that the N-terminal domain of the MEKKs determines the specificity and the strength of activation of various intracellular signaling pathways and cellular responses...
  60. ncbi Raf-1 activation suppresses neuroendocrine marker and hormone levels in human gastrointestinal carcinoid cells
    Rebecca S Sippel
    Dept of Surgery, Univ of Wisconsin Medical School, University of Wisconsin Comprehensive Cancer Center, Madison 53792, USA
    Am J Physiol Gastrointest Liver Physiol 285:G245-54. 2003
    ..These results show that raf-1 induction suppresses neuroendocrine marker and hormone production in human gastrointestinal carcinoid cells via a pathway dependent on MEK activation...
  61. ncbi Relaxin activates the MAP kinase pathway in human endometrial stromal cells
    Qiang Zhang
    Connetics Corporation, 3400 West Bayshore Rd, Palo Alto, California 94303, USA
    J Cell Biochem 85:536-44. 2002
    ..Finally, activation of the MAP kinase pathway was shown to be essential for optimal stimulation of expression of the gene for vascular endothelial growth factor...
  62. ncbi Distinct molecular pathways mediate progesterone-induced growth inhibition and focal adhesion
    Valerie C L Lin
    Department of Clinical Research, Singapore General Hospital, School of Biological Sciences, School, Singapore 637616
    Endocrinology 144:5650-7. 2003
    ....
  63. ncbi MEK inhibition enhances bleomycin A5-induced apoptosis in an oral cancer cell line: signaling mechanisms and therapeutic opportunities
    Li Chiu Yang
    Department of Dentistry, Chung Shan Medical University Hospital, and School of Dentistry, Chung Shan Medical University, Taichung, Taiwan
    J Oral Pathol Med 33:37-45. 2004
    ....
  64. ncbi Identification of MEK- and phosphoinositide 3-kinase-dependent signalling as essential events during Chlamydia pneumoniae invasion of HEp2 cells
    Brian K Coombes
    Father Sean O Sullivan Research Centre, St Joseph s Hospital, Hamilton, Ontario, Canada
    Cell Microbiol 4:447-60. 2002
    ..pneumoniae invasion. These results suggest that activation of specific cell signalling pathways is an essential strategy used by C. pneumoniae to invade epithelial cells...
  65. pmc T6BP, a TRAF6-interacting protein involved in IL-1 signaling
    L Ling
    Tularik Inc, South San Francisco, CA 94080, USA
    Proc Natl Acad Sci U S A 97:9567-72. 2000
    ..T6BP does not seem to play a direct role in activation of IkappaB kinases or Jun N-terminal kinase...
  66. ncbi Identification of a dual specificity kinase that activates the Jun kinases and p38-Mpk2
    A Lin
    Department of Pharmacology, University of California San Diego School of Medicine, La Jolla 92093 0636, USA
    Science 268:286-90. 1995
    ..JNKK also activated another MAPK, p38 (Mpk2; the mammalian homolog of HOG1 from yeast), whose activity is regulated similarly to that of the JNKs...
  67. ncbi Growth factor-dependent activation of the MAPK pathway in human pancreatic cancer: MEK/ERK and p38 MAP kinase interaction in uPA synthesis
    Kyung Hee Lee
    Department of Hemato Oncology, College of Medicine, Yeungnam University, Daegu, Korea
    Clin Exp Metastasis 20:499-505. 2003
    ..These results suggest that ERK activation by HGF might play important roles in the metastasis of pancreatic cancer and the p38 MAPK pathway also involved in the HGF-mediated uPA secretion and metastasis by regulation of ERK pathway...
  68. ncbi Constitutive mitogen-activated protein kinase activation in melanoma is mediated by both BRAF mutations and autocrine growth factor stimulation
    Kapaettu Satyamoorthy
    Wistar Institute, Philadelphia, Pennsylvania 19104, USA
    Cancer Res 63:756-9. 2003
    ..These data suggest that melanoma growth, invasion, and metastasis are attributable to constitutively activated ERK apparently mediated by excessive growth factors through autocrine mechanisms and BRAF kinase activation...
  69. ncbi 1alpha,25-dihydroxyvitamin D3 stimulates activator protein 1 DNA-binding activity by a phosphatidylinositol 3-kinase/Ras/MEK/extracellular signal regulated kinase 1/2 and c-Jun N-terminal kinase 1-dependent increase in c-Fos, Fra1, and c-Jun expression in
    Claus Johansen
    Department of Dermatology, Marselisborg Hospital, University of Aarhus, Denmark
    J Invest Dermatol 120:561-70. 2003
    ....
  70. ncbi Defective stress kinase and Bak activation in response to ionizing radiation but not cisplatin in a non-small cell lung carcinoma cell line
    Kristina Viktorsson
    Cancer Center Karolinska, Department of Oncology Pathology, Karolinska Institute, S 171 76 Stockholm, Sweden
    Exp Cell Res 289:256-64. 2003
    ..Together, the results delineate a mechanism of IR resistance in NSCLC cells and indicate that IR and cisplatin induce Bak modulation and apoptosis via different pathways...
  71. ncbi Mitogenic effects of gastrin-releasing peptide in head and neck squamous cancer cells are mediated by activation of the epidermal growth factor receptor
    Vivian Wai Yan Lui
    Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
    Oncogene 22:6183-93. 2003
    ..These results imply that the mitogenic effects of GRP in HNSCC are mediated by extracellular release of TGF-alpha and require the activation of an EGFR-dependent MEK/MAPK-dependent pathway...
  72. ncbi SUMO-1 modification of the C-terminal KVEKVD of Axin is required for JNK activation but has no effect on Wnt signaling
    Hong Liang Rui
    Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China
    J Biol Chem 277:42981-6. 2002
    ..Taken together, we demonstrate that sumoylation plays a role for Axin to function in the JNK pathway...
  73. ncbi SHP2 regulates IL-2 induced MAPK activation, but not Stat3 or Stat5 tyrosine phosphorylation, in cutaneous T cell lymphoma cells
    Johannes Lundin Brockdorff
    Institute of Medical Microbiology and Immunology, University of Copenhagen, Blegdamsvej 3C, 2200 Copenhagen N, Denmark
    Cytokine 20:141-7. 2002
    ..Furthermore, the results indicate that SHP2 may not be involved in the activation of Stat3 or Stat5 in CTCL cells...
  74. ncbi AKRL1 and AKRL2 activate the JNK pathway
    Takeshi Harada
    Department of Biophysics, Graduate School of Science, Graduate School of Biostudies, Kyoto University, Sakyo ku, Kyoto 606 8502, Japan
    Genes Cells 8:493-500. 2003
    ..Although several upstream components of the JNK pathway, including members of the MAPKKK family have been described, the components lying between the receptors or sensors and JNK have not been fully characterized...
  75. pmc Cell stress and MEKK1-mediated c-Jun activation modulate NFkappaB activity and cell viability
    Isabel Sanchez-Perez
    Instituto de Investigaciones Biomédicas Consejo Superior de Investigaciones Cientificas Universidad Autónoma de Madrid, Spain
    Mol Biol Cell 13:2933-45. 2002
    ..Negative regulation of NFkappaB-dependent transcription by c-jun contributes to cisplatin-induced cell death, which suggests that inhibition of NFkappaB may potentiate the antineoplastic effect of conventional chemotherapeutic agents...
  76. ncbi Akt (protein kinase B) negatively regulates SEK1 by means of protein phosphorylation
    Hee Sae Park
    National Creative Research Initiative Center for Cell Death, Graduate School of Biotechnology, Korea University, Seoul 136 701, Korea
    J Biol Chem 277:2573-8. 2002
    ..Finally, activated Akt inhibited SEK1-mediated apoptosis, and this effect of Akt was prevented by overexpression of SEK(S78A). Taken together, these results suggest that Akt suppresses stress-activated signaling by targeting SEK1...
  77. ncbi Expression of Galpha 13 (Q226L) induces P19 stem cells to primitive endoderm via MEKK1, 2, or 4
    Hsien Yu Wang
    Department of Physiology and Biophysics, University Medical Center, State University of New York, Stony Brook, New York 11794 8661, USA
    J Biol Chem 277:3530-6. 2002
    ....
  78. ncbi A novel Jun N-terminal kinase (JNK)-binding protein that enhances the activation of JNK by MEK kinase 1 and TGF-beta-activated kinase 1
    S Koyano
    Department of Biosciences, School of Science, Kitasato University, 1 15 1 Kitasato, Kanagawa, Japan
    FEBS Lett 457:385-8. 1999
    ..In contrast, JNKBP1 had no or very little effect on the ERK signaling pathway. These results suggest that JNKBP1 functions to facilitate the specific and efficient activation of the JNK signaling pathways...
  79. ncbi Inhibition of extracellular signal-regulated kinase 1/2 phosphorylation and induction of apoptosis by sulindac metabolites
    P L Rice
    Department of Medicine, University of Colorado Health Science Center, Denver 80262, USA
    Cancer Res 61:1541-7. 2001
    ..Inhibition of ERK1/2 activity may, therefore, be a useful biochemical target for the development of chemopreventive and chemotherapeutic drugs for human colon cancer...
  80. ncbi CD40-mediated signaling in monocytic cells: up-regulation of tumor necrosis factor receptor-associated factor mRNAs and activation of mitogen-activated protein kinase signaling pathways
    L L Pearson
    Department of Biology, R6-5, Boehringer Ingelheim Pharmaceuticals, Inc, 900 Ridgebury Road/PO Box 368, Ridgefield, CT 06877, USA
    Int Immunol 13:273-83. 2001
    ..Collectively, these results suggest distinct differences between B cells and monocytic cells in CD40-dependent activation of MAPK pathways...
  81. ncbi Involvement of Asp-Glu-Val-Asp-directed, caspase-mediated mitogen-activated protein kinase kinase 1 Cleavage, c-Jun N-terminal kinase activation, and subsequent Bcl-2 phosphorylation for paclitaxel-induced apoptosis in HL-60 cells
    S G Shiah
    Laboratory of Molecular and Cellular Toxicology, Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan
    Mol Pharmacol 59:254-62. 2001
    ....
  82. ncbi The inhibitory action of sodium arsenite on lipopolysaccharide-induced nitric oxide production in RAW 267.4 macrophage cells: a role of Raf-1 in lipopolysaccharide signaling
    D Chakravortty
    Department of Microbiology and Immunology and Division of Bacterial Toxin, Research Center for Infectious Disease, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan
    J Immunol 166:2011-7. 2001
    ....
  83. pmc MEKK2 gene disruption causes loss of cytokine production in response to IgE and c-Kit ligand stimulation of ES cell-derived mast cells
    T P Garrington
    Department of Pharmacology and University of Colorado Cancer Center, University of Colorado Health Sciences Center, Denver, CO 80206, USA
    EMBO J 19:5387-95. 2000
    ..MEKK2 is the first MAP3K shown to be required for mast cell tyrosine kinase receptor signaling controlling cytokine gene expression...
  84. pmc JNKK1 organizes a MAP kinase module through specific and sequential interactions with upstream and downstream components mediated by its amino-terminal extension
    Y Xia
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California San Diego, La Jolla, California 92093 0636 USA
    Genes Dev 12:3369-81. 1998
    ..These results underscore a role for the amino-terminal extension of MAPKKs in determination of response specificity...
  85. ncbi NESK, a member of the germinal center kinase family that activates the c-Jun N-terminal kinase pathway and is expressed during the late stages of embryogenesis
    K Nakano
    Department of Life Science, Faculty of Bioscience and Biotechnology, Tokyo Institute of Technology, Nagatsuta, Midori ku, Yokohama 226 8501, Japan
    J Biol Chem 275:20533-9. 2000
    ..These results suggest that NESK, a novel activator of the JNK pathway, functions in coupling TRAF2 to the MEKK1 --> MKK4 --> JNK kinase cascade during the late stages of mammalian embryogenesis...
  86. pmc Synergistic interaction of MEK kinase 2, c-Jun N-terminal kinase (JNK) kinase 2, and JNK1 results in efficient and specific JNK1 activation
    J Cheng
    Department of Immunology, The University of Texas, M D Anderson Cancer Center, Houston, Texas 77030, USA
    Mol Cell Biol 20:2334-42. 2000
    ..Thus, formation of a signaling complex through synergistic interaction of a MAPKKK, a MAPKK, and a MAPK molecule like MEKK2-JNKK2-JNK1 is likely to be responsible for the efficient, specific flow of information via MAPK cascades...
  87. ncbi Feedback inhibition of G protein-coupled receptor kinase 2 (GRK2) activity by extracellular signal-regulated kinases
    J A Pitcher
    Howard Hughes Medical Institute, Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 274:34531-4. 1999
    ....
  88. pmc JSAP1, a novel jun N-terminal protein kinase (JNK)-binding protein that functions as a Scaffold factor in the JNK signaling pathway
    M Ito
    Department of Biosciences, School of Science, Kitasato University, Kanagawa 228, Japan
    Mol Cell Biol 19:7539-48. 1999
    ..These results suggest that JSAP1 functions as a scaffold protein in the JNK3 cascade. We also discuss a scaffolding role for JSAP1 in the JNK1 and JNK2 cascades...
  89. pmc TANK potentiates tumor necrosis factor receptor-associated factor-mediated c-Jun N-terminal kinase/stress-activated protein kinase activation through the germinal center kinase pathway
    A I Chin
    Molecular Biology Institute, Jonsson Comprehensive Cancer Center, University of California Los Angeles, 90095, USA
    Mol Cell Biol 19:6665-72. 1999
    ..In addition, CD40 activated endogenous GCKR in primary B cells, implicating GCK family proteins in CD40-mediated B-cell functions...
  90. ncbi Regulation of Gene33 expression by insulin requires MEK-ERK activation
    Adam B Keeton
    Department of Pathology, Division of Molecular and Cellular Pathology, Volker Hall, G019, 1670 University Blvd, University of Alabama at Birmingham, Birmingham, AL 35294 0019, USA
    Biochim Biophys Acta 1679:248-55. 2004
    ..This work suggests that the MEK-ERK, but not the phosphatidylinositol 3-kinase (PI3-K), pathway plays a direct role in insulin regulation of Gene33 transcription and protein expression...
  91. ncbi Activation of SAPK/JNK by TNF receptor 1 through a noncytotoxic TRAF2-dependent pathway
    G Natoli
    Fondazione Andrea Cesalpino and Istituto di I Clinica Medica, Policlinico Umberto I, Viale del Policlinico 155, 00161 Rome, Italy
    Science 275:200-3. 1997
    ..Therefore, SAPK activation occurs through a pathway that is not required for TNF-R1-induced apoptosis...
  92. ncbi Docosahexaenoic acid modulates phorbol ester-induced activation of extracellular signal-regulated kinases 1 and 2 in NIH/3T3 cells
    A Denys
    UPRES Lipides and Nutrition, , , Dijon, France
    Lipids 36:813-8. 2001
    ..In this study, we show for the first time that DHA inhibits MAP kinase ERK1/ERK2) activation and proliferation of NIH/3T3 cells via its inhibitory action on PKC alpha and epsilon isoforms...
  93. ncbi Agonist-specific cross talk between ERKs and p38(mapk) regulates PGI(2) synthesis in endothelium
    R A Houliston
    Department of Veterinary Basic Sciences, The Royal Veterinary College, University of London, London NW1 0TU, United Kingdom
    Am J Physiol Cell Physiol 281:C1266-76. 2001
    ....
  94. ncbi Differential sensitivity to apoptosis between the human small and large intestinal mucosae: linkage with segment-specific regulation of BCL-2 homologs and involvement of signaling pathways
    R Gauthier
    , , , QC, Canada
    J Cell Biochem 82:339-55. 2001
    ..Therefore, these indicate that cell survival is subject to segment-specific control mechanisms along the proximal-distal axis of the intestine...
  95. ncbi Estrogens do not modify MAP kinase-dependent nuclear signaling during stimulation of early G(1) progression in human breast cancer cells
    S Caristi
    Dipartimento di Patologia Generale, , 80138 Napoli, Italy
    Cancer Res 61:6360-6. 2001
    ..Furthermore, hormonal regulation of G(1) gene transcription can occur even without additional activation of the Mek-Erk1/2 pathway by estrogen receptors...
  96. ncbi Human HPK1, a novel human hematopoietic progenitor kinase that activates the JNK/SAPK kinase cascade
    M C Hu
    Department of Experimental Hematology, Amgen, Inc, Thousand Oaks, California 91320, USA
    Genes Dev 10:2251-64. 1996
    ..activation is Rac1/Cdc42-independent. These results indicate that HPK1 is a novel functional activator of the JNK/SAPK signaling pathway...
  97. ncbi Potentiation of signal transduction mitogenesis and cellular proliferation upon binding of receptor-recognized forms of alpha2-macroglobulin to 1-LN prostate cancer cells
    U K Misra
    Department of Pathology, Box 3712, Duke University Medical Center, Durham, NC 27710, USA
    Cell Signal 16:487-96. 2004
    ..We conclude that the growth regulatory effects of ligating the alpha2M* signalling receptor on 1-LN cells are exerted via the onset and crosstalk between the Ras-dependent MAPK and PI 3-kinase/Akt signalling cascades...
  98. ncbi Down-regulation of MEK/ERK signaling by E-cadherin-dependent PI3K/Akt pathway in differentiating intestinal epithelial cells
    Patrick Laprise
    CIHR Group on Functional Development and Physiopathology of the Digestive Tract, Département d Anatomie et Biologie Cellulaire, Faculte de Medecine, Universite de Sherbrooke, Quebec, Canada
    J Cell Physiol 199:32-9. 2004
    ..This mechanism may account for the role of E-cadherin in proliferation/differentiation transition along the crypt-villus axis of the human intestinal epithelium...
  99. ncbi Axin utilizes distinct regions for competitive MEKK1 and MEKK4 binding and JNK activation
    Wen Luo
    Department of Biology, Xiamen University, Xiamen, Fujian 361005, China
    J Biol Chem 278:37451-8. 2003
    ..Our findings will provide new insights into how scaffold proteins mediate ultimate activation of different mitogen-activated protein kinase kinase kinases...
  100. ncbi Phosphorylation of raf-1 by kinase suppressor of ras is inhibited by "MEK-specific" inhibitors PD 098059 and U0126 in differentiating HL60 cells
    X Wang
    Department of Pathology and Laboratory Medicine, UMD-New Jersey Medical School, Newark, New Jersey 07103, USA
    Exp Cell Res 268:294-300. 2001
    ..This suggests great caution in the interpretation of experiments that utilize these pharmacological inhibitors of kinase activity as evidence for a role for the MEK--ERK module in ras or raf-1 signaling...
  101. ncbi Expression of human cystatin A by keratinocytes is positively regulated via the Ras/MEKK1/MKK7/JNK signal transduction pathway but negatively regulated via the Ras/Raf-1/MEK1/ERK pathway
    H Takahashi
    Department of Dermatology, Asahikawa Medical College, Asahikawa, Hokkaido 078 8510, Japan
    J Biol Chem 276:36632-8. 2001
    ..These results indicate that the expression of cystatin A is regulated via mitogen-activated protein kinase pathways positively by Ras/MEKK1/MKK7/JNK and negatively by Ras/Raf/MEK1/ERK...

Research Grants37

  1. MOLECULAR MEDIATORS OF DIABETIC RENAL HYPERTROPHY
    John Kyriakis; Fiscal Year: 2002
    ..These studies, they hope, will expand our knowledge of signal transduction in the diabetic kidney and contribute to the development of novel treatments for diabetic nephropathy using signaling components as targets. ..
  2. CELL GROWTH REGULATION VIA THE MEKK/SAPK CASCADE
    Dennis Templeton; Fiscal Year: 2003
    ..We propose to characterize the mechanism by which stress signals interact with the cyclin B/cdc2 kinase. ..
  3. NIH--EGF/NEU RECEPTOR SIGNAL TRANSDUCTION
    Gary Johnson; Fiscal Year: 2001
    ..4) Define the role of Cbl in ErbB1 signaling and the mediation of survival. ..
  4. MEKK2/3-MEK5 Interaction/Activation/ERK5 Pathway(RMI)
    BRUCE CUEVAS; Fiscal Year: 2005
    ....
  5. Nutritional Regulation of Fetal Liver Development
    PHILIP GRUPPUSO; Fiscal Year: 2008
    ..Furthermore, we anticipate that our findings will relate to diverse areas of liver biology, including the hepatic response to liver injury, hepatic carcinogenesis, and liver stem cell biology. [unreadable] [unreadable]..
  6. DIET AND SOMATIC MUTATIONS IN COLON CANCER
    MARTHA OR MARTY SLATTERY; Fiscal Year: 2007
    ..e. p53, K-ras, and microsatellite instability). Differences in colon and rectal tumors will be compared. Additionally data from rectal tumors will be combined with that from colon tumors to define disease pathways. ..
  7. Signaling Mechanisms of TCDD-induced AHR Activation
    Ying Xia; Fiscal Year: 2007
    ..abstract_text> ..
  8. Role of Km23 in Ovarian Cancer
    KATHLEEN MULDER; Fiscal Year: 2007
    ..We hypothesize that the latter two types of studies will assist in the development of screens by which to identify novel agents for the treatment of ovarian cancer [unreadable] [unreadable] [unreadable]..
  9. Cyclic GMP Phosphodiesterase in Signaling
    Hsien Yu Wang; Fiscal Year: 2007
    ..These studies are highly relevant to signaling as well as to elucidation of basis for human diseases in which alterations in signaling pathways translate into aberrant biology. ..
  10. Prevention of neointimal thickening by Mst1
    Junichi Sadoshima; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable]..
  11. 'Death' and 'MAPK' pathways with myocardial ischemia
    Junichi Sadoshima; Fiscal Year: 2001
    ..Our study will contribute to the understanding of the mechanism of cardiac myocyte apoptosis by hR and may provide clues to prevent myocyte loss and reduced cardiac function after myocardial I/R. ..
  12. Prostate Cancer Metastasis Suppressor: Role of RKIP
    Evan Keller; Fiscal Year: 2008
    ..when completed, we hope this work will lead to a better understanding of the mechanisms through which RKIP suppresses metastasis and hopefully identify specific targets to inhibit metastasis. [unreadable] [unreadable]..
  13. Modifiers of Cancer Risk in BRCA 1/2 Mutation Carriers
    Timothy Rebbeck; Fiscal Year: 2008
    ..Our substantial multidisciplinary experience will therefore allow us to readily translate basic science and epidemiological data to clinically relevant information. ..
  14. Genetics of Longevity and Age-Sensitive Traits in Mice
    Richard Miller; Fiscal Year: 2008
    ..abstract_text> ..
  15. Rheb GTPase as chemotherapeutic target for brain tumors
    LAWRENCE QUILLIAM; Fiscal Year: 2009
    ..They will address the molecular basis of non-Ras action of FTIs and demonstrate the value of targeting Rheb in cancer therapy. ..
  16. Surgical Studies of GI Peptides - Mechanisms of Action
    MARK HELLMICH; Fiscal Year: 2009
    ..Aim 2: To define the role of MAPKs in CCK-BRwt- and CCK-BRi4sv-mediated intracellular signal transduction. Aim 3: To determine the effects of CCK-BRi4sv and CCK-BRwt expression on gene expression. ..
  17. PDEF and survivin: cancer prognosis, initiation, progression and metastasis
    Fengzhi Li; Fiscal Year: 2010
    ..These studies may provide novel approaches for cancer prognosis and personalized medicine, by considering survivin and PDEF as interconnected biomarkers and targets. ..
  18. Ethnic difference in prostate cancer
    Timothy R Rebbeck; Fiscal Year: 2010
    ....
  19. A PROSPECTIVE STUDY OF ALASKA NATIVES & AMERICAN INDIANS
    MARTHA OR MARTY SLATTERY; Fiscal Year: 2006
    ..The AIAN cohort will serve as a resource to enhance research and training activities of AIAN students interested in health research, health education, and general public health. ..
  20. Prophytactic surgery in carriers of BRCA 1/2 mutations
    Timothy R Rebbeck; Fiscal Year: 2010
    ..These studies will motivate future studies of BRCA1/2-associated breast tumor biology, prevention, and treatment. ..
  21. MECHANISMS OF TGF BETA SIGNALING
    KATHLEEN MULDER; Fiscal Year: 2001
    ....
  22. ETIOLOGIC HETEROGENEITY IN LATE ONSET BREAST CANCER
    Timothy Rebbeck; Fiscal Year: 2001
    ..The results of these analyses will be used to attempt to elucidate the complex, multifactorial aetiology of late onset breast cancer. ..
  23. ETHANOL MEDIATED OSTEOPOROSIS AND INTERLEUKIN 6
    Evan Keller; Fiscal Year: 2002
    ....
  24. AGING, GENE EXPRESSION AND OXIDATIVE STRESS
    Evan Keller; Fiscal Year: 2002
    ....
  25. MITOGEN ACTIVATED PROTEIN KINASES AND BREAST CANCER
    KALADHAR REDDY; Fiscal Year: 2003
    ..The long term goal is the identification of molecular events underlying tumor progression that are potential targets for the development of rational therapeutic agents. ..
  26. GENETICS OF AGE SENSITIVE TRAITS IN MICE
    Richard Miller; Fiscal Year: 2003
    ..At best, the program may permit the localization of loci that influence multiple age-sensitive domains and are thus plausible candidates for genes that regulate the rate of aging per se. ..
  27. FOUR-CORNERS BREAST AND ENDOMETRIAL CANCER STUDY
    MARTHA OR MARTY SLATTERY; Fiscal Year: 2003
    ..C-peptide, glycosylated hemoglobin, IGF-1, and IGFBP3 will be evaluated with respect to breast and endometrial cancer in a subset of women. ..
  28. C/EBPB And Mitotic Clonal Expansion During Adipogenesis
    Qi Qun Tang; Fiscal Year: 2004
    ..identify the kinase(s) that catalyzes this/these phosphorylation/s and to determine how the kinase(s) is regulated. -determine the role of C/EBP-beta in mitotic clonal expansion and how phosphorylation of C/EBP-beta affects this role...
  29. WILD DERIVED MOUSE STOCKS--NEW MODELS FOR AGING RESEARCH
    Richard Miller; Fiscal Year: 2004
    ....
  30. Prevention of cardiac cell death by Mst1 inhibitor
    Junichi Sadoshima; Fiscal Year: 2005
    ..abstract_text> ..
  31. Studies of a Novel CCK-B/Gastrin Receptor Splice Variant
    MARK HELLMICH; Fiscal Year: 2005
    ..Furthermore, these studies may, in the future, provide the basis for the development of innovative therapeutic strategies for the treatment of peptide hormone-sensitive cancers. ..
  32. VEGF and bone remodeling in skeletal metastases
    Evan Keller; Fiscal Year: 2005
    ..In this aim, we will test which VEGF isoform contributes to CaP cells' osteoblastic activity. We will also evaluate if VEGF induces this activity through MAPK. ..
  33. DEVELOPMENT OF MATURE ZEBRAFISH AS AN ANIMAL MODEL
    Evan Keller; Fiscal Year: 2006
    ....
  34. Hepatocyte Proliferation During Development: Role of p38
    PHILIP GRUPPUSO; Fiscal Year: 2006
    ..We anticipate that these studies will provide novel insights into the regulation of hepatocyte proliferation during normal development and in the mature rat. ..
  35. Growth Factors and Colon Cancer
    MARTHA OR MARTY SLATTERY; Fiscal Year: 2006
    ..This study builds on a unique existing resource to study genetic and environmental associations with colorectal cancer. It will provide insight into colon cancer etiology and therefore avenues to disease prevention. ..
  36. Anti-aging and Stress Resistance by Sir2
    Junichi Sadoshima; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable]..
  37. Survivin expression and cancer cell drug resistance
    Fengzhi Li; Fiscal Year: 2008
    ..unreadable] [unreadable]..