MKK4

Summary

Gene Symbol: MKK4
Description: mitogen-activated protein kinase kinase 4
Alias: JNKK, JNKK1, MAPKK4, MEK4, MKK4, PRKMK4, SAPKK-1, SAPKK1, SEK1, SERK1, SKK1, dual specificity mitogen-activated protein kinase kinase 4, JNK-activated kinase 1, JNK-activating kinase 1, MAP kinase kinase 4, MAPK/ERK kinase 4, MAPKK 4, MEK 4, SAPK/ERK kinase 1, c-Jun N-terminal kinase kinase 1, stress-activated protein kinase kinase 1
Species: human

Top Publications

  1. ncbi Actin-binding protein-280 binds the stress-activated protein kinase (SAPK) activator SEK-1 and is required for tumor necrosis factor-alpha activation of SAPK in melanoma cells
    A Marti
    Diabetes Unit and Medical Services, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 021291, USA
    J Biol Chem 272:2620-8. 1997
  2. ncbi Activation of JNK3 alpha 1 requires both MKK4 and MKK7: kinetic characterization of in vitro phosphorylated JNK3 alpha 1
    J Lisnock
    Department of Molecular Design and Diversity, Merck Research Laboratories, P O Box 2000, Rahway, New Jersey 07065, USA
    Biochemistry 39:3141-8. 2000
  3. ncbi Tobacco smoke control of mucin production in lung cells requires oxygen radicals AP-1 and JNK
    Erin Gensch
    Department of Anatomy, Cardiovascular Research Institute and Biomedical Sciences Graduate Program, University of California, San Francisco, California 94143, USA
    J Biol Chem 279:39085-93. 2004
  4. ncbi Activation of DNA methyltransferase 1 by EBV LMP1 Involves c-Jun NH(2)-terminal kinase signaling
    Chia Lung Tsai
    Graduate Institute of Basic Medical Sciences and Pathology Core, Chang Gung Molecular Medicine Research Center, Chang Gung University, Taiwan, Republic of China
    Cancer Res 66:11668-76. 2006
  5. pmc The role of JNK and p38 MAPK activities in UVA-induced signaling pathways leading to AP-1 activation and c-Fos expression
    Amy L Silvers
    Department of Radiation Oncology, Arizona Cancer Center, The University of Arizona, Tucson, AZ, USA
    Neoplasia 5:319-29. 2003
  6. pmc Activation of MEK-1 and SEK-1 by Tpl-2 proto-oncoprotein, a novel MAP kinase kinase kinase
    A Salmeron
    Division of Cellular Immunology, National Institute of Medical Research, London, UK
    EMBO J 15:817-26. 1996
  7. ncbi Characterization of signaling pathways activated by the interleukin 1 (IL-1) receptor homologue T1/ST2. A role for Jun N-terminal kinase in IL-4 induction
    Elizabeth K Brint
    Cytokine Research Group, Department of Biochemistry, Trinity College, Dublin 2, Ireland
    J Biol Chem 277:49205-11. 2002
  8. ncbi TAB1beta (transforming growth factor-beta-activated protein kinase 1-binding protein 1beta ), a novel splicing variant of TAB1 that interacts with p38alpha but not TAK1
    Baoxue Ge
    Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 278:2286-93. 2003
  9. ncbi Phosphorylation and inactivation of myeloid cell leukemia 1 by JNK in response to oxidative stress
    Seiji Inoshita
    Laboratory of Cell Signaling, Department of Hard Tissue Engineering, Division of Bio Matrix, Graduate School, Tokyo Medical and Dental University, 1 5 45 Yushima, Bunkyo ku, Japan
    J Biol Chem 277:43730-4. 2002
  10. ncbi Tumor necrosis factor signaling to stress-activated protein kinase (SAPK)/Jun NH2-terminal kinase (JNK) and p38. Germinal center kinase couples TRAF2 to mitogen-activated protein kinase/ERK kinase kinase 1 and SAPK while receptor interacting protein assoc
    T Yuasa
    Diabetes Research Laboratory, Medical Services, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
    J Biol Chem 273:22681-92. 1998

Research Grants

  1. Jonathan M Kurie; Fiscal Year: 2016
  2. KALEN RAY DIONNE; Fiscal Year: 2014
  3. c-Jun N-terminal kinase and joint destruction in RA
    Gary S Firestein; Fiscal Year: 2012
  4. Bioflavonoid Effects on EGF Signaling and Cell Cycle Pathways in Prostate Cancer
    BARRY MATTHEW MARKAVERICH; Fiscal Year: 2013
  5. REGULATION OF A C JUN KINASE BY A NOVEL TUMOR PROMOTER
    ELIZABETH WATTENBERG; Fiscal Year: 2001
  6. Jun Chen; Fiscal Year: 2015
  7. p38 MAPK as a therapeutic target in Myelodysplastic syndrome
    Amit Verma; Fiscal Year: 2009
  8. Molecular Inhibitors of Prostate Cancer Metastasis
    REBECCA LEIGH FARMER; Fiscal Year: 2011
  9. Prostate Cancer Metastatic Colonization: Role of MKK4
    Carrie W Rinker-Schaeffer; Fiscal Year: 2013
  10. Interaction of anti-angiogenic and cytotoxic therapies in colorectal cancer
    PETER J O'DWYER; Fiscal Year: 2013

Detail Information

Publications270 found, 100 shown here

  1. ncbi Actin-binding protein-280 binds the stress-activated protein kinase (SAPK) activator SEK-1 and is required for tumor necrosis factor-alpha activation of SAPK in melanoma cells
    A Marti
    Diabetes Unit and Medical Services, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 021291, USA
    J Biol Chem 272:2620-8. 1997
    ..ABP-280 participates in TNF-alpha signal transduction to SAPKs, in part through the binding of SEK-1...
  2. ncbi Activation of JNK3 alpha 1 requires both MKK4 and MKK7: kinetic characterization of in vitro phosphorylated JNK3 alpha 1
    J Lisnock
    Department of Molecular Design and Diversity, Merck Research Laboratories, P O Box 2000, Rahway, New Jersey 07065, USA
    Biochemistry 39:3141-8. 2000
    ..In this study we investigated the in vitro activation of JNK3 alpha 1 by MAP kinase kinase 4 (MKK4), MAP kinase kinase 7 (MKK7), and the combination of MKK4 + MKK7...
  3. ncbi Tobacco smoke control of mucin production in lung cells requires oxygen radicals AP-1 and JNK
    Erin Gensch
    Department of Anatomy, Cardiovascular Research Institute and Biomedical Sciences Graduate Program, University of California, San Francisco, California 94143, USA
    J Biol Chem 279:39085-93. 2004
    ..Taken together with our earlier results, these data indicate that the induction of mucin by smoke is the combined effect of mutually independent, reactive oxygen species activation of both EGFR and JNK...
  4. ncbi Activation of DNA methyltransferase 1 by EBV LMP1 Involves c-Jun NH(2)-terminal kinase signaling
    Chia Lung Tsai
    Graduate Institute of Basic Medical Sciences and Pathology Core, Chang Gung Molecular Medicine Research Center, Chang Gung University, Taiwan, Republic of China
    Cancer Res 66:11668-76. 2006
    ..38%), suggesting that overexpression of these proteins is observed in NPC tumor. Overall, these results support a mechanistic link between JNK-AP-1 signaling and DNA methylation induced by the EBV oncogene product LMP1...
  5. pmc The role of JNK and p38 MAPK activities in UVA-induced signaling pathways leading to AP-1 activation and c-Fos expression
    Amy L Silvers
    Department of Radiation Oncology, Arizona Cancer Center, The University of Arizona, Tucson, AZ, USA
    Neoplasia 5:319-29. 2003
    ..Targeted inhibition of these MAPKs with their selective pharmacologic inhibitors may be effective chemopreventive strategies for UVA-induced nonmelanoma skin cancer...
  6. pmc Activation of MEK-1 and SEK-1 by Tpl-2 proto-oncoprotein, a novel MAP kinase kinase kinase
    A Salmeron
    Division of Cellular Immunology, National Institute of Medical Research, London, UK
    EMBO J 15:817-26. 1996
    ..Tpl-2, therefore, is a MAP kinase kinase kinase which can activate two MAP kinase pathways. After Raf and Mos, Tpl-2 is the third serine/threonine oncoprotein kinase that has been shown to function as a direct activator of MEK-1...
  7. ncbi Characterization of signaling pathways activated by the interleukin 1 (IL-1) receptor homologue T1/ST2. A role for Jun N-terminal kinase in IL-4 induction
    Elizabeth K Brint
    Cytokine Research Group, Department of Biochemistry, Trinity College, Dublin 2, Ireland
    J Biol Chem 277:49205-11. 2002
    ....
  8. ncbi TAB1beta (transforming growth factor-beta-activated protein kinase 1-binding protein 1beta ), a novel splicing variant of TAB1 that interacts with p38alpha but not TAK1
    Baoxue Ge
    Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA
    J Biol Chem 278:2286-93. 2003
    ....
  9. ncbi Phosphorylation and inactivation of myeloid cell leukemia 1 by JNK in response to oxidative stress
    Seiji Inoshita
    Laboratory of Cell Signaling, Department of Hard Tissue Engineering, Division of Bio Matrix, Graduate School, Tokyo Medical and Dental University, 1 5 45 Yushima, Bunkyo ku, Japan
    J Biol Chem 277:43730-4. 2002
    ..JNK-dependent phosphorylation and thus inactivation of Mcl-1 may be one of the mechanisms through which oxidative stress induces cellular damage...
  10. ncbi Tumor necrosis factor signaling to stress-activated protein kinase (SAPK)/Jun NH2-terminal kinase (JNK) and p38. Germinal center kinase couples TRAF2 to mitogen-activated protein kinase/ERK kinase kinase 1 and SAPK while receptor interacting protein assoc
    T Yuasa
    Diabetes Research Laboratory, Medical Services, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
    J Biol Chem 273:22681-92. 1998
    ..Thus, TRAF2 initiates SAPK and p38 activation by binding two proximal protein kinases: GCK and RIP. GCK and RIP, in turn, signal by binding MAPKKKs upstream of the SAPKs and p38s...
  11. ncbi Ser/Thr protein phosphatase 5 inactivates hypoxia-induced activation of an apoptosis signal-regulating kinase 1/MKK-4/JNK signaling cascade
    Guofei Zhou
    Department of Biochemistry and Molecular Biology, College of Medicine, University of South Alabama, Mobile, Alabama 36688, USA
    J Biol Chem 279:46595-605. 2004
    ..domain of ASK-1, and studies with siRNA targeting PP5 indicate that PP5 acts to suppress the phosphorylation of MKK4 (Thr-261), JNK (Thr-183/Tyr-185), and c-Jun (Ser-63) without affecting the activating phosphorylation of p38 MAPK (..
  12. ncbi Independent human MAP-kinase signal transduction pathways defined by MEK and MKK isoforms
    B Derijard
    Department of Biochemistry and Molecular Biology, University of Massachusetts Medical School, Worcester 01605
    Science 267:682-5. 1995
    ..Two human MAP kinase kinases (MKK3 and MKK4) were cloned that phosphorylate and activate p38 MAP kinase...
  13. ncbi Human mitogen-activated protein kinase kinase 4 as a candidate tumor suppressor
    D H Teng
    Myriad Genetics, Inc, Salt Lake City, Utah 84108, USA
    Cancer Res 57:4177-82. 1997
    ..A mammalian member of this kinase family, MKK4/JNKK1/SEK1, has been reported to link upstream MEKK1 to downstream stress-activated protein kinase/JNK1 and p38 mitogen-..
  14. ncbi Alterations in pancreatic, biliary, and breast carcinomas support MKK4 as a genetically targeted tumor suppressor gene
    G H Su
    Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205 2196, USA
    Cancer Res 58:2339-42. 1998
    Mitogen-activated protein kinase (MAPK) kinase 4 (MKK4) is a component of a stress and cytokine-induced signal transduction pathway involving MAPK proteins...
  15. 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
    ..In similar cotransfection studies, JSAP1 also interacted with SEK1 MAPKK and MEKK1 MAPKKK, which are involved in the JNK cascades...
  16. pmc Synergistic activation of stress-activated protein kinase 1/c-Jun N-terminal kinase (SAPK1/JNK) isoforms by mitogen-activated protein kinase kinase 4 (MKK4) and MKK7
    Y Fleming
    MRC Protein Phosphorylation Unit, Department of Biochemistry, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    Biochem J 352:145-54. 2000
    ..Here we report that MKK4 shows a striking preference for the tyrosine residue (Tyr-185), and MKK7 a striking preference for the threonine ..
  17. ncbi Mitogen-activated protein kinase kinase 4 metastasis suppressor gene expression is inversely related to histological pattern in advancing human prostatic cancers
    H L Kim
    Department of Surgery, The University of Chicago, Illinois 60637, USA
    Cancer Res 61:2833-7. 2001
    ..A. Yoshida et al., Cancer Res., 59: 5483-5487) that mitogen-activated protein kinase kinase 4 (MKK4) can suppress AT6.1 rat prostate cancer metastases in vivo...
  18. 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
    ..Here we report that SEK1 is a target of Akt in intact cells...
  19. doi Cardiac-specific deletion of mkk4 reveals its role in pathological hypertrophic remodeling but not in physiological cardiac growth
    Wei Liu
    Faculty of Medical and Human Sciences, University of Manchester, Manchester, United Kingdom
    Circ Res 104:905-14. 2009
    ..pathological cardiac hypertrophy and heart failure; however, the regulatory mechanism whereby the upstream kinase MKK4 activates these signaling cascades in the heart is unknown...
  20. pmc MEK4 function, genistein treatment, and invasion of human prostate cancer cells
    Li Xu
    Department of Medicine, Robert H Lurie Cancer Center and Center for Drug Discovery and Chemical Biology of Northwestern University, Chicago, IL60610, USA
    J Natl Cancer Inst 101:1141-55. 2009
    ..We investigated the target for genistein in prostate cancer cells...
  21. doi Functional and clinicopathological analysis of loss of MKK4 expression in endometrial cancer
    Masako Ishikawa
    Department of Obstetrics and Gynecology, Shimane University School of Medicine, Izumo, Japan
    Oncology 79:238-46. 2010
    In the current study, we investigated the mechanism relating downregulation of mitogen-activated protein kinase kinase-4 (MKK4) expression to the development of endometrial cancer.
  22. doi MKK4 acts as a potential tumor suppressor in ovarian cancer
    Shamima Yeasmin
    Department of Obstetrics and Gynecology, Shimane University School of Medicine, Enyacho 89 1, Izumo, Shimane, 6938501, Japan
    Tumour Biol 32:661-70. 2011
    Our previous studies indicate that loss of MKK4 expression is associated with the progression of ovarian cancer. However, direct evidence that MKK4 inhibits the malignant phenotype of ovarian cancer cells is limited...
  23. ncbi MEKK1 binds raf-1 and the ERK2 cascade components
    M Karandikar
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9041, USA
    J Biol Chem 275:40120-7. 2000
    ..In this study we demonstrate that endogenous MEKK1 binds to endogenous ERK2, MEK1, and another MEKK level kinase, Raf-1, suggesting that it can assemble all three proteins of the ERK2 MAP kinase module...
  24. ncbi Regulation of the interleukin-1-induced signaling pathways by a novel member of the protein phosphatase 2C family (PP2Cepsilon)
    Ming Guang Li
    Department of Biochemistry, Institute of Development, Aging, and Cancer, Tohoku University, 4 1 Seiryomachi, Aoba ku, Sendai 980 8575, Japan
    J Biol Chem 278:12013-21. 2003
    ..of PP2Cepsilon inhibited the IL-1- and TAK1-induced activation of mitogen-activated protein kinase kinase 4 (MKK4)-c-Jun N-terminal kinase or MKK3-p38 signaling pathway. PP2Cepsilon dephosphorylated TAK1 in vitro...
  25. ncbi Homozygous deletion of MKK4 in ovarian serous carcinoma
    Kentaro Nakayama
    Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21231, USA
    Cancer Biol Ther 5:630-4. 2006
    ..4 Mb which harbored a candidate tumor suppressor gene, mitogen-activated protein kinase kinase-4 (MKK4)...
  26. doi Proteomic analysis of GTP cyclohydrolase 1 multiprotein complexes in cultured normal adult human astrocytes under both basal and cytokine-activated conditions
    Anna Chiarini
    Department of Biomedical and Surgical Sciences, Histology and Embryology Unit, University of Verona Medical School, Verona, Italy
    Proteomics 9:1850-60. 2009
    ..These findings provide a first enticing glimpse into the intricate mechanisms regulating GCH1 activation by proinflammatory cytokines in NAHA, and may have therapeutic implications...
  27. doi Hematopoietic progenitor kinase 1, mitogen-activated protein/extracellular signal-related protein kinase kinase kinase 1, and phosphomitogen-activated protein kinase kinase 4 are overexpressed in extramammary Paget disease
    Yue Qian
    Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
    Am J Dermatopathol 33:681-6. 2011
    ..transforming growth factor-β activated kinase 1 (TAK1), and phosphomitogen-activated protein kinase kinase 4 (p-MKK4) to the development of EMPD...
  28. ncbi Phosphorylation-dependent scaffolding role of JSAP1/JIP3 in the ASK1-JNK signaling pathway. A new mode of regulation of the MAP kinase cascade
    Hiroshi Matsuura
    Laboratory of Cell Signaling, Graduate School, Tokyo Medical and Dental University, 1 5 45 Yushima, Bunkyo ku, Tokyo 113 8549, Japan
    J Biol Chem 277:40703-9. 2002
    ..ASK1 phosphorylated JSAP1 in vitro and in vivo, and the phosphorylation facilitated interactions of JSAP1 with SEK1/MKK4, MKK7 and JNK3...
  29. pmc Gene transfer of the JNK interacting protein-1 protects dopaminergic neurons in the MPTP model of Parkinson's disease
    X G Xia
    Neurodegeneration Laboratory, Department of Neurology and Medical School, , Hoppe-Seyler Strasse 3, , Germany
    Proc Natl Acad Sci U S A 98:10433-8. 2001
    ..MPTP/MPP(+) led to the sequential phosphorylation and activation of JNK kinase (MKK4), JNK, and c-Jun, the activation of caspases, and apoptosis...
  30. doi Neuroprotection of ethanol against ischemia/reperfusion-induced brain injury through decreasing c-Jun N-terminal kinase 3 (JNK3) activation by enhancing GABA release
    S H Qi
    School of Life Science and Biotechnology, China Pharmaceutical University, 24 Tongjia Street, Nanjing, 210009, People s Republic of China
    Neuroscience 167:1125-37. 2010
    ..PSD-95 and mixed-lineage kinase 3, MLK3) module induced by cerebral ischemia and the activation of the MLK3-MKK4/7-JNK (mitogen-activated protein kinase kinase 4/7, MKK4/7) cascade...
  31. pmc Impaired CD28-mediated interleukin 2 production and proliferation in stress kinase SAPK/ERK1 kinase (SEK1)/mitogen-activated protein kinase kinase 4 (MKK4)-deficient T lymphocytes
    H Nishina
    Amgen Institute and Ontario Cancer Institute, Department of Medical Biophysics and Immunology, University of Toronto, M5G 2C1 Toronto, Ontario, Canada
    J Exp Med 186:941-53. 1997
    The dual specific kinase SAPK/ERK1 kinase (SEK1; mitogen-activated protein kinase kinase 4/Jun NH2 terminal kinase [ JNK] kinase) is a direct activator of stress-activated protein kinases ([SAPKs]/JNKs) in response to CD28 costimulation, ..
  32. ncbi Vaccination alone or in combination with pyridostigmine promotes and prolongs activation of stress-activated kinases induced by stress in the mouse brain
    Dechun Wang
    Department of Pharmacology, Boston University School of Medicine, Massachusetts 02118, USA
    J Neurochem 93:1010-20. 2005
    ..In our previous studies, we found that stress induces activation of mitogen activated protein-kinase kinase 4 (MKK4) and c-Jun-N-terminal kinase (JNK) in the mouse brain (Liu et al. 2004)...
  33. pmc c-Jun NH2-terminal kinase activating kinase 1/mitogen-activated protein kinase kinase 4-mediated inhibition of SKOV3ip.1 ovarian cancer metastasis involves growth arrest and p21 up-regulation
    Tamara Lotan
    Department of Pathology, The University of Chicago, 5841 South Maryland Avenue, MC6038, Chicago, IL 60637, USA
    Cancer Res 68:2166-75. 2008
    ..laboratory identified c-Jun NH(2)-terminal kinase activating kinase 1/mitogen-activated protein kinase kinase 4 (JNKK1/MKK4) as a metastasis suppressor protein in a mouse xenograft model of experimental i.p. ovarian cancer metastasis...
  34. ncbi Inhibition of MLK3-MKK4/7-JNK1/2 pathway by Akt1 in exogenous estrogen-induced neuroprotection against transient global cerebral ischemia by a non-genomic mechanism in male rats
    Ran Wang
    Research Center for Biochemistry and Molecular Biology, Jiangsu Key Laboratory for Brain Disease Bioinformation, Xuzhou Medical College, Xuzhou, China
    J Neurochem 99:1543-54. 2006
    ..and reduced the activation of mixed-lineage kinase 3 (MLK3), mitogen-activated protein kinase kinase 4/7 (MKK4/7), and c-Jun N-terminal kinase 1/2 (JNK1/2) in the hippocampal CA1 subfield during reperfusion after 15 min of ..
  35. doi Phloroglucinol (1,3,5-trihydroxybenzene) protects against ionizing radiation-induced cell damage through inhibition of oxidative stress in vitro and in vivo
    Kyoung Ah Kang
    Jeju National University School of Medicine and Applied Radiological Science Research Institute, Jeju si 690 756, Republic of Korea
    Chem Biol Interact 185:215-26. 2010
    ..effect of phloroglucinol was exerted via inhibition of mitogen-activated protein kinase kinase-4 (MKK4/SEK1), c-Jun NH(2)-terminal kinase (JNK) and activator protein-1 (AP-1) cascades induced by radiation exposure...
  36. ncbi Astrocyte protection of neurons: role of transforming growth factor-beta signaling via a c-Jun-AP-1 protective pathway
    Krishnan M Dhandapani
    Institute of Molecular Medicine and Genetics, Program in Neurobiology, and Department of Neurology, School of Medicine, Medical College of Georgia, Augusta, Georgia 30912, USA
    J Biol Chem 278:43329-39. 2003
    ..activation of the upstream kinases, c-Jun N-terminal kinase (JNK) and mitogen-activated protein kinase kinase-4 (MKK4) was also demonstrated...
  37. ncbi Eicosapentaenoic acid inhibits UV-induced MMP-1 expression in human dermal fibroblasts
    Hyeon Ho Kim
    Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea
    J Lipid Res 46:1712-20. 2005
    ..and also inhibited the UV-induced activation of ERK and JNK by inhibiting ERK kinase (MEK1) and SAPK/ERK kinase 1 (SEK1) activation, respectively...
  38. doi Identification of small-molecule inhibitors of the JIP-JNK interaction
    Tracy Chen
    Department of Target Biology, Pfizer Research Technology Center, Cambridge, MA 02139, USA
    Biochem J 420:283-94. 2009
    ..Its partner, JIP1 (JNK-interacting protein 1), serves a scaffolding function that facilitates JNK1 activation by MKK4 [MAPK (mitogen-activated protein kinase) kinase 4] and MKK7 (MAPK kinase 7)...
  39. ncbi Dual roles for c-Jun N-terminal kinase in developmental and stress responses in cerebellar granule neurons
    E T Coffey
    Turku Centre for Biotechnology, Abo Akademi University and University of Turku, BioCity, FIN 20521 Turku, Finland
    J Neurosci 20:7602-13. 2000
    ..We identify a minor stress-sensitive pool of JNK that translocates with mitogen-activated protein kinase kinase-4 (MKK4) into the nucleus...
  40. ncbi c-Jun NH2-terminal kinase-related Na+/H+ exchanger isoform 1 activation controls hexokinase II expression in benzo(a)pyrene-induced apoptosis
    Laurence Huc
    Institut National de la Santé et de la Recherche Médicale U620, Universite Rennes 1, IFR 140, 2 Avenue du Pr Leon Bernard, Rennes, France
    Cancer Res 67:1696-705. 2007
    ..Our results indicate that the mitogen-activated protein kinase kinase 4/c-Jun NH(2)-terminal kinase (MKK4/JNK) pathway was a link between BaP-induced H(2)O(2) production and NHE1 activation...
  41. ncbi Mitogen-activated protein kinase kinase 7 is activated during low potassium-induced apoptosis in rat cerebellar granule neurons
    Linda Trotter
    Discovery Biology, Pfizer Global Research and Development, Sandwich, Kent CT13 9NJ, UK
    Neurosci Lett 320:29-32. 2002
    ..Using an immune-complex kinase assay, we measured the activation of MKK4 and MKK7 in low potassium (LK)-induced apoptosis of rat cerebellar granule neurons (CGN)...
  42. ncbi Specific amino acid deficiency alters the expression of genes in human melanoma and other tumor cell lines
    G G Meadows
    Cancer Prevention and Research Center, Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Pullman, WA 99164 6510, USA
    J Nutr 131:3047S-50S. 2001
    ..and phosphorylation of mitogen-activated protein kinase kinase 4 (MKK4)/stress-activated protein/Erk kinase (SEK1), a metastasis suppressor gene...
  43. ncbi Expression and mutation analyses of MKK4, a candidate tumour suppressor gene encoded by chromosome 17p, in human gastric adenocarcinoma
    K S Chae
    Department of Pathology, College of Medicine, Kyung Hee University, Seoul 130 701, South Korea
    Eur J Cancer 38:2048-57. 2002
    Homozygous deletion or somatic mutations of mitogen-activated protein kinase kinase 4 (MKK4), a candidate tumour suppressor gene located at 17p11, have been observed in many types of human tumours...
  44. doi Loss of MKK4 expression in ovarian cancer: a potential role for the epithelial to mesenchymal transition
    Shamima Yeasmin
    Department of Obstetrics and Gynecology, Shimane University School of Medicine, Izumo, Shimane 6938501, Japan
    Int J Cancer 128:94-104. 2011
    ..current study, we investigated the mechanism relating downregulation of mitogen-activated protein kinase kinase 4 (MKK4) expression to development of ovarian cancer...
  45. doi A functional variant (-1304T>G) in the MKK4 promoter contributes to a decreased risk of lung cancer by increasing the promoter activity
    Bin Liu
    The Institute for Chemical Carcinogenesis, Guangzhou Medical College, People s Republic of China
    Carcinogenesis 31:1405-11. 2010
    Mitogen-activated protein kinase kinase 4 (MKK4) is a critical mediator of stress-activated protein kinase signals that regulate apoptosis, inflammations and tumorigenesis. Several polymorphisms have been identified in the MKK4 gene...
  46. ncbi Role of mitogen-activated protein kinase kinase 4 in cancer
    A J Whitmarsh
    Faculty of Life Sciences, University of Manchester, Manchester, UK
    Oncogene 26:3172-84. 2007
    Mitogen-activated protein (MAP) kinase kinase 4 (MKK4) is a component of stress activated MAP kinase signaling modules...
  47. pmc Targeted deletion of the mitogen-activated protein kinase kinase 4 gene in the nervous system causes severe brain developmental defects and premature death
    Xin Wang
    Faculty of Life Sciences, Wellcome Trust Center for Cell Matrix Research, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, United Kingdom
    Mol Cell Biol 27:7935-46. 2007
    ..Its activity is increased upon phosphorylation by the MAPK kinases MKK4 and MKK7...
  48. pmc Increased expression of IRE1alpha and stress-related signal transduction proteins in ischemia-reperfusion injured retina
    Natsuyo Hata
    Department of Ophthalmology and Visual Science, Chiba University, Graduate School of Medicine, Chuo Ku, Chiba, Japan
    Clin Ophthalmol 2:743-52. 2008
    ..expression of ER stress-related factors IRE1alpha, apoptosis signal-regulating kinase 1 (ASK1), SAPK/ERK kinase 1 (SEK1) and c-Jun N-terminal kinase (JNK) is associated with the damaged retinal neurons induced by ischemia-reperfusion ..
  49. pmc The mitogen-activated protein kinase kinase 4 has a pro-oncogenic role in skin cancer
    Katherine G Finegan
    Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester, United Kingdom
    Cancer Res 70:5797-806. 2010
    The mitogen-activated protein kinase (MAPK) kinase 4 (MKK4) is a nonredundant component of stress-activated MAPK signaling modules...
  50. ncbi Human mitogen-activated protein kinase kinase 7 (MKK7) is a highly conserved c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) activated by environmental stresses and physiological stimuli
    I N Foltz
    The Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada
    J Biol Chem 273:9344-51. 1998
    ..and to a newly identified ortholog from Caenorhabditis elegans (54% identity), and was more distantly related to MKK4, MKK3, and MKK6. MKK7 phosphorylated and activated JNK1 but failed to activate p38 MAPK in co-expression studies...
  51. pmc Role of the stress-activated protein kinases in endothelin-induced cardiomyocyte hypertrophy
    G Choukroun
    Renal Unit, and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Clin Invest 102:1311-20. 1998
    ....
  52. ncbi A novel mechanism of JNK1 activation. Nuclear translocation and activation of JNK1 during ischemia and reperfusion
    Y Mizukami
    Department of Legal Medicine, Yamaguchi University School of Medicine, Yamaguchi, Japan
    J Biol Chem 272:16657-62. 1997
    ..Based on fractionation and immunohistochemical analyses, an upstream kinase for JNK1, SAPK/ERK kinase 1 (SEK1), is constantly present in both the nucleus and cytoplasm throughout ischemia and reperfusion, whereas an upstream ..
  53. doi Cocoa procyanidins attenuate 4-hydroxynonenal-induced apoptosis of PC12 cells by directly inhibiting mitogen-activated protein kinase kinase 4 activity
    Eun Sun Cho
    Department of Agricultural Biotechnology, Seoul National University, Republic of Korea
    Free Radic Biol Med 46:1319-27. 2009
    ..Activation of c-Jun N-terminal protein kinase (JNK) and mitogen-activated protein kinase kinase 4 (MKK4) was attenuated by CPF and procyanidin B2...
  54. ncbi Isolation of MEK5 and differential expression of alternatively spliced forms
    J M English
    Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas 75235 9041, USA
    J Biol Chem 270:28897-902. 1995
    ..MEK5 is more closely related to MEK1 and MEK2 than to the other known mammalian MEKs, MKK3 and MKK4. MEK5 is thought to lie in an uncharacterized MAP kinase pathway, because MEK5 does not phosphorylate the ERK/MAP ..
  55. ncbi Signal transduction of nitric oxide donor-induced protection in hydrogen peroxide-mediated apoptosis in H9C2 cardiomyoblasts
    H J Chae
    Institute of Cardiovascular Research, Chonkuk National University Medical School, Chonju, South Korea
    Immunopharmacol Immunotoxicol 23:187-204. 2001
    ..Furthermore, the dominant negative JNK and SEK1-expressing cells displayed a marked decrease in a number of apoptotic cells...
  56. pmc A human homolog of the yeast Ssk2/Ssk22 MAP kinase kinase kinases, MTK1, mediates stress-induced activation of the p38 and JNK pathways
    M Takekawa
    Dana Farber Cancer Institute and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    EMBO J 16:4973-82. 1997
    ..MTK1 overexpression also activated the MKK3, MKK6 and SEK1 MAPKKs, but not the MEK1 MAPKK. Furthermore, MTK1 phosphorylated and activated MKK6 and SEK1 in vitro...
  57. doi The Parkinson disease-associated protein kinase LRRK2 exhibits MAPKKK activity and phosphorylates MKK3/6 and MKK4/7, in vitro
    Christian Johannes Gloeckner
    Department of Protein Science, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Neuherberg, Germany
    J Neurochem 109:959-68. 2009
    ..Our findings present evidence of a new class of molecular targets for mutant LRRK2 that link to neurotoxicity, cellular stress, cytoskeletal dynamics and vesicular transport...
  58. pmc Role of MEKK2-MEK5 in the regulation of TNF-alpha gene expression and MEKK2-MKK7 in the activation of c-Jun N-terminal kinase in mast cells
    K Chayama
    Division of Basic Sciences, Department of Pediatrics, and the Program in Molecular Signal Transduction, National Jewish Medical and Research Center, Denver, CO 80206, USA
    Proc Natl Acad Sci U S A 98:4599-604. 2001
    ..We report here that MAP kinase kinase 4 (MKK4) gene disruption does not affect either MAP kinase activation or cytokine gene expression in response ..
  59. pmc A novel SAPK/JNK kinase, MKK7, stimulated by TNFalpha and cellular stresses
    T Moriguchi
    Institute for Virus Research, Graduate School of Science, Kyoto University, Sakyo ku, Kyoto 606 01, Japan
    EMBO J 16:7045-53. 1997
    ..To date, SEK1/MKK4, one of the MAP kinase kinase (MAPKK) family of molecules, is the only SAPK/JNK kinase that has been cloned...
  60. pmc Selective activation and functional significance of p38alpha mitogen-activated protein kinase in lipopolysaccharide-stimulated neutrophils
    J A Nick
    Department of Medicine, Program in Molecular Signal Transduction, National Jewish Medical and Research Center, Denver, Colorado 80206, USA
    J Clin Invest 103:851-8. 1999
    ..Although MKK3, MKK4, and MKK6 all activated p38 MAPk in experimental models, only MKK3 was found to activate recombinant p38 MAPk in ..
  61. pmc The MLK family mediates c-Jun N-terminal kinase activation in neuronal apoptosis
    Z Xu
    Department of Pathology and Center for Neurobiology and Behavior, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
    Mol Cell Biol 21:4713-24. 2001
    ..in part mediated through a pathway that includes Rac1 and Cdc42, mitogen-activated protein kinase kinases 4 and 7 (MKK4 and -7), c-Jun N-terminal kinases (JNKs), and c-Jun...
  62. ncbi Convergence of CpG DNA- and BCR-mediated signals at the c-Jun N-terminal kinase and NF-kappaB activation pathways: regulation by mitogen-activated protein kinases
    Ae Kyung Yi
    Children s Foundation Research Center at Le Bonheur Children s Medical Center, Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38103, USA
    Int Immunol 15:577-91. 2003
    ..CpG DNA augments BCR-mediated signals for the activation of mitogen-activated protein kinase (MAPK) kinase (MKK)3, MKK4 and MKK6, and their subsequent downstream effectors c-Jun N-terminal kinase (JNK) and p38, but does not enhance ..
  63. pmc Regulation of the JNK pathway by TGF-beta activated kinase 1 in rheumatoid arthritis synoviocytes
    Deepa R Hammaker
    Division of Rheumatology, Allergy and Immunology, UCSD School of Medicine, Gilman Dr, La Jolla, CA 92093, USA
    Arthritis Res Ther 9:R57. 2007
    ..It is phosphorylated by at least two upstream kinases, the mitogen-activated protein kinase kinases (MEK) MKK4 and MKK7, which are, in turn, phosphorylated by MEK kinases (MEKKs)...
  64. pmc A non-redundant role for Drosophila Mkk4 and hemipterous/Mkk7 in TAK1-mediated activation of JNK
    Peter Geuking
    Institut fur Molekularbiologie, Universitat Zurich, Zurich, Switzerland
    PLoS ONE 4:e7709. 2009
    ..JNK activity is controlled by two MAPK kinases (MAPKK), Mkk4 and Mkk7. Mkk7 plays a prominent role upon Tumor Necrosis Factor (TNF) stimulation...
  65. pmc Activation of ASK1, downstream MAPKK and MAPK isoforms during cardiac ischaemia
    Stephen J Harding
    Department of Biochemistry, Henry Wellcome Building, University of Leicester, Leicester, UK
    Biochim Biophys Acta 1802:733-40. 2010
    ..Ischaemia strongly activated p38alpha but not the JNK pathway. The MAPKKs, MKK3, MKK4 and MKK6 have previously been identified as potential upstream activators of p38; however, in the ischaemic ..
  66. pmc The MKK7 gene encodes a group of c-Jun NH2-terminal kinase kinases
    C Tournier
    Howard Hughes Medical Institute and Program in Molecular Medicine and Department of Biochemistry and Molecular Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    Mol Cell Biol 19:1569-81. 1999
    ..Two MAPKKs, MKK4 and MKK7, have been identified as JNK activators...
  67. pmc Stress- and cell type-dependent regulation of transfected c-Jun N-terminal kinase and mitogen-activated protein kinase kinase isoforms
    L Butterfield
    Department of Medicine, University of Colorado Health Sciences Center, 4200 E Ninth Ave, Denver, CO 80262, USA
    Biochem J 338:681-6. 1999
    ..In addition, HA-tagged forms of the dual-specificity mitogen-activated protein kinase kinases (MKKs), MKK4 and MKK7, which are specific activators of the JNK enzymes, were similarly expressed...
  68. ncbi Ebselen inhibits tumor necrosis factor-alpha-induced c-Jun N-terminal kinase activation and adhesion molecule expression in endothelial cells
    Masanori Yoshizumi
    Department of Pharmacology, The University of Tokushima School of Medicine, Tokushima 770 8503, Japan
    Exp Cell Res 292:1-10. 2004
    ..factor 2 (TRAF2)-ASK1 complex formation and phosphorylation of stress-activated protein kinase ERK kinase 1 (SEK1), which is an upstream signaling molecule of JNK...
  69. doi Diverse physiological functions of MKK4 and MKK7 during early embryogenesis
    Yoichi Asaoka
    Department of Developmental and Regenerative Biology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113 8510, Japan
    J Biochem 148:393-401. 2010
    ..Two MAPKKs that are crucial transducers upstream of JNK signalling are MKK4 and MKK7...
  70. pmc Surviving the passage: Non-canonical stromal targeting of an Arabidopsis mitogen-activated protein kinase kinase
    Marcus A Samuel
    Michael Smith Laboratories University of British Columbia Vancouver Canada
    Plant Signal Behav 3:6-12. 2008
    ..Unexpectedly, the imported MKK4 protein was not processed through stromal peptidase-dependent cleavage of the N-terminal signal peptide, thus ..
  71. pmc Delphinidin suppresses ultraviolet B-induced cyclooxygenases-2 expression through inhibition of MAPKK4 and PI-3 kinase
    Jung Yeon Kwon
    Major in Biomodulation, Department of Agricultural Biotechnology, Seoul National University, Seoul 151 742, Republic of Korea
    Carcinogenesis 30:1932-40. 2009
    ..A pull-down assay using delphinidin-Sepharose beads revealed that delphinidin binds directly with MAPKK4 or PI-3K in a manner that was competitive with adenosine triphosphate...
  72. pmc Novel and expanded roles for MAPK signaling in Arabidopsis stomatal cell fate revealed by cell type-specific manipulations
    Gregory R Lampard
    Department of Biology, Stanford University, Stanford, CA 94305, USA
    Plant Cell 21:3506-17. 2009
    ..In Arabidopsis thaliana, signaling networks that contain MAPK kinases MKK4/5 and MAPKs MPK3/6 function in abiotic and biotic stress responses and regulate embryonic and stomatal development...
  73. pmc Activation of Erk and JNK MAPK pathways by acute swim stress in rat brain regions
    Chang peng Shen
    Department of Psychiatry, New York University School of Medicine, 550 First Ave, MHL HN511, New York, NY 10016, USA
    BMC Neurosci 5:36. 2004
    ..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...
  74. ncbi Response of non-small cell lung cancer cells to the inhibitors of phosphatidylinositol 3-kinase/Akt- and MAPK kinase 4/c-Jun NH2-terminal kinase pathways: an effective therapeutic strategy for lung cancer
    Ho Young Lee
    Department of Thoracic Head and Neck Medical Oncology, University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Clin Cancer Res 11:6065-74. 2005
    ..This study was designed to explore whether inhibition of these pathways effectively inhibits NSCLC tumor growth in vivo...
  75. ncbi Direct activation of mitochondrial apoptosis machinery by c-Jun N-terminal kinase in adult cardiac myocytes
    Hiroki Aoki
    Department of Molecular Cardiovascular Biology, Yamaguchi University School of Medicine, Minami Kogushi, Ube, Yamaguchi 755 8505, Japan
    J Biol Chem 277:10244-50. 2002
    ..was abrogated by dominant negative stress-activated protein kinase/extracellular signal-regulated kinase kinase-1 (SEK1)-mediated inhibition of the JNK pathway, whereas activation of the JNK pathway by constitutively active SEK1 was ..
  76. ncbi PP2A regulates upstream members of the c-jun N-terminal kinase mitogen-activated protein kinase signaling pathway
    Bin Zhao
    Division of Pediatric Critical Care Medicine, Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio, USA
    Shock 29:181-8. 2008
    ..activation of JNK by LPS proceeds through the MAPK kinase kinase MEKK-1 and, subsequently, the MAPK kinases MKK4 and/or MKK7...
  77. ncbi Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways
    H Ichijo
    Department of Biochemistry, The Cancer Institute, Tokyo, Japanese Foundation for Cancer Research, 1 37 1 Kami Ikebukuro, Toshima ku, Tokyo 170, Japan
    Science 275:90-4. 1997
    ..kinase (MAPKKK), termed ASK1, was identified that activated two different subgroups of MAP kinase kinases (MAPKK), SEK1 (or MKK4) and MKK3/MAPKK6 (or MKK6), which in turn activated stress-activated protein kinase (SAPK, also known as ..
  78. ncbi Characterization of the mitogen-activated protein kinase kinase 4 (MKK4)/c-Jun NH2-terminal kinase 1 and MKK3/p38 pathways regulated by MEK kinases 2 and 3. MEK kinase 3 activates MKK3 but does not cause activation of p38 kinase in vivo
    K Deacon
    Department of Cell Physiology and Pharmacology, University of Leicester School of Medicine, P O Box 138, Medical Sciences Building, University Road, Leicester LE1 9HN, United Kingdom
    J Biol Chem 272:14489-96. 1997
    ..were used to examine the regulation by MEKK2 and MEKK3 of the dual specificity MAP kinase kinases, MKK3 and MKK4. MKK3 specifically phosphorylates and activates p38, whereas MKK4 phosphorylates and activates both p38 and JNK...
  79. pmc Differential activation of stress-activated protein kinase kinases SKK4/MKK7 and SKK1/MKK4 by the mixed-lineage kinase-2 and mitogen-activated protein kinase kinase (MKK) kinase-1
    A Cuenda
    MRC Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, Dundee DD1 4HN, Scotland, U K and Trescowthick Research Centre, Peter MacCallum Cancer Institute, Melbourne, Victoria 3000, Australia
    Biochem J 333:11-5. 1998
    ..Here we demonstrate that MLK2 activates SAPK kinase-1 (SKK1)/MAPK kinase 4 (MKK4) and SKK4/MKK7, the two known direct activators of SAPK1/JNK (both in transfection studies and in vitro)...
  80. ncbi Expression of mixed lineage kinase 2 in germ cells of the testis
    D R Phelan
    Trescowthick Research Centre, Peter MacCallum Cancer Institute, Melbourne, Victoria, Australia
    Mol Reprod Dev 52:135-40. 1999
    ..kinases/c-jun N-terminal kinases (SAPK/JNKs) through direct phosphorylation of their upstream activator, SEK1/JNKK. We have examined expression of both MLK2 and SEK1/JNKK RNAs in the rat testis at various times during postnatal ..
  81. ncbi Beta-arrestin 2: a receptor-regulated MAPK scaffold for the activation of JNK3
    P H McDonald
    Howard Hughes Medical Institute and Department of Medicine, Duke University Medical Center, Box 3821, Durham, NC 27710, USA
    Science 290:1574-7. 2000
    ..Thus, beta-arrestin 2 acts as a scaffold protein, which brings the spatial distribution and activity of this MAPK module under the control of a GPCR...
  82. pmc Susceptibility of mitogen-activated protein kinase kinase family members to proteolysis by anthrax lethal factor
    G Vitale
    Centro CNR Biomembrane and Dipartimento di Scienze Biomediche, Universita di Padova, Via Trieste 75, 35121 Padova, Italy
    Biochem J 352:739-45. 2000
    ..extended the study of LF proteolytic specificity to all known MAPKK family members and found that LF also cleaves MKK4, MKK6 and MKK7, but not MEK5. The peptide bonds hydrolysed by LF within all MAPKKs were identified...
  83. pmc Involvement of alpha-PAK-interacting exchange factor in the PAK1-c-Jun NH(2)-terminal kinase 1 activation and apoptosis induced by benzo[a]pyrene
    S Yoshii
    First Department of Pathology, Hamamatsu University School of Medicine, Hamamatsu 431 3192, Japan
    Mol Cell Biol 21:6796-807. 2001
    ..alphaPIX (Delta SH3), which lacks the ability to bind PAK, kinase-negative PAK1 (K299R), and kinase-negative SEK1 (K220A, K224L) inhibited B(a)P-triggered JNK1 activation...
  84. ncbi Prevention of kidney ischemia/reperfusion-induced functional injury, MAPK and MAPK kinase activation, and inflammation by remote transient ureteral obstruction
    Kwon Moo Park
    Medical Services, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
    J Biol Chem 277:2040-9. 2002
    ..N-terminal stress-activated protein kinase 1/2 (JNK1/2), p38, mitogen-activated protein kinase (MAPK) kinase 4 (MKK4), and MKK3/6...
  85. pmc Oxidation-triggered c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein (MAP) kinase pathways for apoptosis in human leukaemic cells stimulated by epigallocatechin-3-gallate (EGCG): a distinct pathway from those of chemically induced and recep
    Koichi Saeki
    Department of Haematology, Research Institute, International Medical Centre of Japan, 1 21 1, Toyama, Shinjuku ku, Tokyo 162 8655, Japan
    Biochem J 368:705-20. 2002
    ..both apoptosis and JNK/p38 activation by EGCG, and EGCG-induced activation of MAP kinase kinase (MKK) 3/6, MKK4 and apoptosis-regulating kinase 1 (ASK1) was suppressed by NAC...
  86. ncbi Activation mechanism of c-Jun amino-terminal kinase in the course of endodermal differentiation of P19 embryonic carcinoma cells
    Tada Aki Kudo
    Department of Biochemistry, Institute of Development, Aging and Cancer, Tohoku University, 4 1 Seiryo machi, Aoba ku, Sendai 980 8575, Japan
    FEBS Lett 539:29-33. 2003
    ..In this study we demonstrated that of the two upstream protein kinases of JNK, only MKK4 activity was substantially enhanced in the endodermally differentiating P19 cells...
  87. ncbi Role of the ASK1-SEK1-JNK1-HIPK1 signal in Daxx trafficking and ASK1 oligomerization
    Jae J Song
    Department of Surgery and Pharmacology, Hillman Cancer Center, University of Pittsburgh, 5117 Centre Avenue, Pittsburgh, PA 15213, USA
    J Biol Chem 278:47245-52. 2003
    ..phosphorylation of Daxx occurred during glucose deprivation, and its phosphorylation was mediated through the ASK1-SEK1-JNK1-HIPK1 signal transduction pathway...
  88. ncbi Resveratrol inhibits phorbol myristate acetate-induced matrix metalloproteinase-9 expression by inhibiting JNK and PKC delta signal transduction
    Ju Hyung Woo
    Department of Immunology, School of Medicine, Keimyung University, 194 DongSan Dong Jung Gu, South Korea
    Oncogene 23:1845-53. 2004
    ..Therefore, we conclude that the MMP-9 inhibition activity of resveratrol and its inhibition of JNK and PKC-delta may have a therapeutic potential, given that a novel means of controlling growth and invasiveness of tumors...
  89. ncbi Protein kinase R (PKR) interacts with and activates mitogen-activated protein kinase kinase 6 (MKK6) in response to double-stranded RNA stimulation
    Aristobolo M Silva
    Departments of Cancer Biology and Immunology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    J Biol Chem 279:37670-6. 2004
    ..We found that the p38 MAPK activator MKK6, but not its close relatives MKK3 or MKK4, exhibited an increased affinity for PKR following the exposure of cells to poly(rI:rC), a dsRNA analog...
  90. ncbi Negative regulation of MEKK1-induced signaling by glutathione S-transferase Mu
    Kanghyun Ryoo
    National Creative Research Initiative Center for Cell Death, School of Life Sciences and Biotechnology, Korea University, Seoul 136 701, South Korea
    J Biol Chem 279:43589-94. 2004
    ..Overexpressed GST M1-1 interfered with the binding of MEKK1 to SEK1 in transfected HEK293 cells. Furthermore, GST M1-1 suppressed MEKK1-mediated apoptosis...
  91. ncbi Requirement of MKK4 and MKK7 for CdCl2- or HgCl2-induced activation of c-Jun NH2-terminal kinase in mouse embryonic stem cells
    Masato Matsuoka
    Department of Hygiene and Public Health, School of Medicine, Tokyo Women s Medical University, 8 1 Kawada cho, Shinjuku ku, Tokyo 162 8666, Japan
    Toxicol Lett 152:175-81. 2004
    ..metals, the phosphorylation status and the activity of JNK were examined in mouse embryonic stem (ES) cells lacking MKK4 or MKK7 following exposure to CdCl(2) or HgCl(2)...
  92. ncbi G alpha 13 signals via p115RhoGEF cascades regulating JNK1 and primitive endoderm formation
    Yi Nan Lee
    Department of Physiology and Biophysics, Diabetes and Metabolic Diseases Research Center, State University of New York Stony Brook, New York 11794 8661, USA
    J Biol Chem 279:54896-904. 2004
    ..The signal linkage map from MEKK1/MEKK4 to MEK1/MKK4 to JNK is obligate in this G alpha(13)-mediated pathway, whereas that between G alpha(13) and MEKKs is not known...
  93. ncbi Mitogen-activated protein kinases and mitogen-activated protein kinase phosphatases mediate the inhibitory effects of all-trans retinoic acid on the hypertrophic growth of cardiomyocytes
    Ants Palm-Leis
    Division of Molecular Cardiology, Department of Internal Medicine, Scott and White and The Texas A and M University System Health Science Center, College of Medicine, Temple, Texas 76504, USA
    J Biol Chem 279:54905-17. 2004
    ..protein kinase kinases (MKKs), because RA had no effect on stretch- or Ang II-induced phosphorylation of MEK1/2, MKK4, and MKK3/6...
  94. ncbi DNA damage in transcribed genes induces apoptosis via the JNK pathway and the JNK-phosphatase MKP-1
    Mohamed Hamdi
    Department of Molecular Cell Biology, Leiden University Medical Center, Wassenaarseweg 72, 2333AL Leiden, The Netherlands
    Oncogene 24:7135-44. 2005
    ..and is established through repression of the JNK-phosphatase MKP-1 rather than by activation of the JNK kinases MKK4 and 7...
  95. ncbi WNT/PCP signaling pathway and human cancer (review)
    Masaru Katoh
    Genetics and Cell Biology Section, National Cancer Center Research Institute, Tsukiji 5 chome, Chuo Ku, Tokyo 104 0045, Japan
    Oncol Rep 14:1583-8. 2005
    ..cascade through Formin homology proteins DAAM1 and DAAM2, and to the JNK signaling cascade through MAPKKKs and MAPKK4/7. Dishevelled-independent WNT/ PCP signals are transduced to the NLK signaling cascade through MAP3K7 (TAK1)...
  96. ncbi Transcriptional regulation of human CC chemokine CCL15 gene by NF-kappaB and AP-1 elements in PMA-stimulated U937 monocytoid cells
    Yong Hyun Shin
    Graduate School of Biotechnology and Institute of Life Sciences and Resources, Kyung Hee University, Yongin 449 701, Korea
    Biochim Biophys Acta 1732:38-42. 2005
    ..Specific inhibitors for MAPK pathways and expression of dominant negative MKK4 or JNK1 reduced PMA-induced transcriptional activation of CCL15...
  97. pmc Varicella-zoster virus infection of human fibroblast cells activates the c-Jun N-terminal kinase pathway
    Heidi J Zapata
    Department of Microbiology and Immunology, State University of New York Upstate Medical University, 750 E Adams St, Syracuse, NY 13210, USA
    J Virol 81:977-90. 2007
    ..The two main activators of JNK are MKK4 and MKK7, and levels of their active, phosphorylated forms also increased...
  98. ncbi Structural polymorphism of chromodomains in Chd1
    Masahiko Okuda
    Graduate School of Supramolecular Biology, Yokohama City University, Tsurumi ku, Yokohama 230 0045, Japan
    J Mol Biol 365:1047-62. 2007
    ..In human CHD1, both chromodomains are essential for specific binding to a K4 methylated histone H3 (H3 MeK4) peptide and are found to bind cooperatively in the crystal structure...
  99. pmc Stomatal development and patterning are regulated by environmentally responsive mitogen-activated protein kinases in Arabidopsis
    Huachun Wang
    Division of Biological Sciences, University of Missouri, Columbia, Missouri 65211, USA
    Plant Cell 19:63-73. 2007
    ..MPK6, two environmentally responsive mitogen-activated protein kinases (MAPKs), and their upstream MAPK kinases, MKK4 and MKK5, are key regulators of stomatal development and patterning...
  100. ncbi Post-transcriptional regulation of human inducible nitric-oxide synthase expression by the Jun N-terminal kinase
    Riku Korhonen
    Department of Pharmacology, Johannes Gutenberg University, Mainz, Germany
    Mol Pharmacol 71:1427-34. 2007
    ..Moreover, the modulation of JNK signaling by SP600125 or siRNA did not change p38 phosphorylation. In summary, the results suggest that JNK regulates human iNOS expression by stabilizing iNOS mRNA possibly by a TTP-dependent mechanism...
  101. pmc Microarray analysis of oxidative stress regulated genes in mesencephalic dopaminergic neuronal cells: relevance to oxidative damage in Parkinson's disease
    Vellareddy Anantharam
    Parkinson s Disorder Research Laboratory, Iowa Center for Advanced Neurotoxicology, Department of Biomedical Sciences, Iowa State University, Ames, IA 50011 1250, USA
    Neurochem Int 50:834-47. 2007
    ..in genes encoding pro- or anti-apoptotic proteins included up-regulation of BIK, PAWR, STAT5B, NPAS2, Jun B, MEK4, CCT7, PPP3CC, and PSDM3, while key down-regulated genes included BNIP3, NPTXR, RAGA, STK6, YWHAH, and MAP2K1...

Research Grants53

  1. Jonathan M Kurie; Fiscal Year: 2016
    ..metastasis is MAP2K4, which encodes the stress- and cytokine-regulated mitogen activated protein kinase kinase-4 (MKK4)...
  2. KALEN RAY DIONNE; Fiscal Year: 2014
    ..originating at the cell membrane may initiate intracellular JNK activation by proceeding through the Fas-Daxx-ASK1-Sek1-JNK apoptotic pathway...
  3. c-Jun N-terminal kinase and joint destruction in RA
    Gary S Firestein; Fiscal Year: 2012
    ..Two upstream kinases, MKK4 and MKK7, can independently activate JNK and initiate protease and cytokine gene expression...
  4. Bioflavonoid Effects on EGF Signaling and Cell Cycle Pathways in Prostate Cancer
    BARRY MATTHEW MARKAVERICH; Fiscal Year: 2013
    ..cancer cells in addition to a number of genes involved in the EGF Signaling Pathway (EGFR, GRB2, SOS, RasGAP, MKK4, c-Fos, JNK1)...
  5. REGULATION OF A C JUN KINASE BY A NOVEL TUMOR PROMOTER
    ELIZABETH WATTENBERG; Fiscal Year: 2001
    ..part of a protein kinase cascade that has recently been shown to regulate JNK activation (the Rac, Cdc42/Pak1/MEKK1/SEK1/JNK pathway). Specific Aim 3. Determine if palytoxin stimulates c-Jun transcriptional activity via JNK...
  6. Jun Chen; Fiscal Year: 2015
    ..ASK1 is a 160-kDa serine/threonine protein kinase that activates both JNK and p38 MAPK pathways by phosphorylating MKK4/MKK7 and MKK3/MKK6, respectively...
  7. p38 MAPK as a therapeutic target in Myelodysplastic syndrome
    Amit Verma; Fiscal Year: 2009
    ..evaluation of the activation status of the small G-protein Rac1 and the upstream Map kinase kinases, MKK3, MKK6 and MKK4, as well as the activation of the downstream effectors MapKapK-2, MapKapK-3, and Msk1...
  8. Molecular Inhibitors of Prostate Cancer Metastasis
    REBECCA LEIGH FARMER; Fiscal Year: 2011
    ..we will make structural modifications to the isoflavanone core to promote selective binding to the enzyme MEK4, which is a known member of the p38 MAP kinase signaling family and the biological target of genistein...
  9. Prostate Cancer Metastatic Colonization: Role of MKK4
    Carrie W Rinker-Schaeffer; Fiscal Year: 2013
    ..The PI identified a novel role in metastatic colonization for JNKK1, a dual-specificity kinase that activates the JNK and/or p38 MAPKs in response to extracellular stimuli...
  10. Interaction of anti-angiogenic and cytotoxic therapies in colorectal cancer
    PETER J O'DWYER; Fiscal Year: 2013
    ..kinase (JNK) determines sensitivity or resistance to treatment, in particular at the level of the kinases SEK1 and MKK7, activation of which demonstrates opposing influences...
  11. Vsevolod V Gurevich; Fiscal Year: 2015
    ..the structural basis of arrestin-dependent activation of pro-apoptotic JNK family kinases and their activators MKK4/7 using biochemical and biophysical methods...
  12. Signaling Complexes in Renal Epithelial Cells
    Richard Miller; Fiscal Year: 2005
    ..Filamin also binds to variety of other signaling molecules including SEKI (MKK4), caveolin, the dopamine 02 receptor, Rho GTPases, SMADs and a- and Beta integrins, suggesting that it can act as a ..
  13. PROTEIN TYROSINE KINASES AND MAST CELL ACTIVATION
    Toshiaki Kawakami; Fiscal Year: 2001
    ..3) Since preliminary data suggest the presence of a Btk-dependent, but not SEK1-dependent, pathway for JNK/SAPK activation induced by FceRI cross-linking, this possibility will be investigated in ..
  14. PATHOPHYSIOLOGY OF RENAL TUBULAR CELLS
    Frank Lee; Fiscal Year: 2002
    ..Finally, MEKK1 can also activate the MAP2K MKK4 which, in turn, activates the stress induced kinase JNK...
  15. APOPTOSIS & CELL CYCLE IN BREAST & OVARIAN CANCER CELLS
    Jay Wimalasena; Fiscal Year: 2003
    ..a variety of cell lines including MCF-7 breast cancer cells and BR ovarian cells is mediated through a Ras/Rac/Ask1/JNKK/JNK signal transduction pathway...
  16. LPS-INDUCED NEUTROPHIL ACCUMULATION IN THE LUNG
    G Worthen; Fiscal Year: 2007
    ..by cross-talk between p38 MAP kinase and JNK, We suggest that p38 activates PP2A, a phosphatase that inactivates MKK4. Using a variety of techniques to detect molecular interactions and modify expression levels in human and murine ..
  17. HPK1-Mediated Lymphocyte Signal Transduction Mechanisms
    Tse Hua Tan; Fiscal Year: 2005
    ..Receptors -> adaptors, kinases -> HPK1 (also called MAP4K1) -> MAP3Ks (MEKK1, TAK1, MLK3) -> MAP2Ks (MKK4, MKKT) !->JNK -> cell activation or apoptosis...
  18. HPK1 MEDIATED T CELL SIGNAL TRANSDUCTION MECHANISMS
    Tse Hua Tan; Fiscal Year: 2002
    ..about the HPK1 signaling pathway is as follows: TCR, CD28 yields Adaptors yields HPK1 yields MEKK1, TAK1 yields MKK4, MKK7 yields JNK yields T-Cell Activation/Apoptosis...
  19. MOLECULAR MECHANISMS OF TNF ALPHA INDUCED CYTOTOXICITY
    Anning Lin; Fiscal Year: 2001
    ..a publication report that TNF-alpha-induced apoptosis can be blocked by the dominant negative mutants of c-Jun and JNKK. The specific aims of this proposal are: 1) to investigate the effect of FADD on the JNK cascade in TNF-alpha-..
  20. APOPTOSIS IN PROSTATE CANCER
    Edward Gelmann; Fiscal Year: 2001
    ..The dominant negative constructs will block RB interaction with ABL, ABL kinase, CAP kinase, SEK1 kinase and JUN.
  21. MLK3 function in neurofibromatosis tumor cells
    John Kyriakis; Fiscal Year: 2009
    ..Alternatively, merlin could repress the recruitment of MLK3 by Rho family GTPases. In Aim 3, we will use biochemical and molecular biological methods to explore these possibilities. ..
  22. Induction of immunological paralysis by CpG DNA
    Ae Kyung Yi; Fiscal Year: 2008
    ..abstract_text> ..
  23. Mechanisms of chemopreventive effect of resveratrol
    Zigang Dong; Fiscal Year: 2009
    ..Our long-term goal is to identify the molecular mechanism explaining the anti-tumor effect exhibited by resveratrol. Such knowledge will help in developing better chemopreventive agents with fewer side effects. ..
  24. NEGATIVE REGULATORS OF MYELOPOIESIS
    Barbara Hoffman; Fiscal Year: 2009
    ..This knowledge should provide novel tools for designing drugs to promote differentiation and/or apoptosis of leukemic cells. ..
  25. INHIBITION OF CARCINOGENESIS BY TEA AND TEA CONSTITUENTS
    Zigang Dong; Fiscal Year: 2010
    ..abstract_text> ..
  26. Gadd 45 in the Response of Hematopoietic Cells to Stress
    Dan A Liebermann; Fiscal Year: 2010
    ....
  27. Study on Ultraviolet-induced Signal Transduction
    Zigang Dong; Fiscal Year: 2010
    ..These preclinical studies are designed to lead to the development of new strategies for the chemoprevention of human skin cancers. ..
  28. THE STRESS-ACTIVATED PROTEIN KINASE PATHWAY
    John M Kyriakis; Fiscal Year: 2010
    ..These studies will provide important details of a previously unknown signaling pathway required for inflammatory responses. ..
  29. TARGETS OF AMINO ACID RESTRICTION IN PROSTATE CANCER
    Gary G Meadows; Fiscal Year: 2009
    ..This research could serve as the basis for future development of more specific antimetastatic, anti-invasive, apoptosis-based therapies for human prostate cancer. ..
  30. ROLE OF PKD IN LEUKOCYTE ACTIVATION BY CPG DNA
    Ae Kyung Yi; Fiscal Year: 2002
    ..This proposed study would enhance our understanding of how CpG motifs in bacterial DNA break immune tolerance and contribute to chrome inflammatory autoimmune diseases such as arthritis. ..
  31. Mechanisms on metastasis and survival in alcoholic mice
    Gary G Meadows; Fiscal Year: 2010
    ..Flow cytometric and ELISA assays will be used to determine lymphocyte populations, surface and intracellular marker expression, cytokine producing cells, and cytokine concentrations. ..
  32. MECHANISMS OF TGF BETA SIGNALING
    KATHLEEN MULDER; Fiscal Year: 2001
    ....
  33. ALCOHOL OXYGEN RADICAL INTERACTIONS AS DETECTED BY ESR
    Arthur Cederbaum; Fiscal Year: 2001
    ..These studies will provide new information on the ability of NO to modulate CYP2El catalytic activity, generation of reactive intermediates, and ethanol and PUFA toxicity. ..
  34. Molecular basis of arsenic-induced cell transformation
    Zigang Dong; Fiscal Year: 2007
    ..Such knowledge will facilitate the design of more effective and specific strategies with fewer side effects for chemoprevention of arsenic-induced cancer. ..
  35. MyD118, CR6 and GADD45 in Genotoxic Stress
    Dan Liebermann; Fiscal Year: 2003
    ....
  36. Degradation of Human CYP2E1 by the Proteasome
    Arthur Cederbaum; Fiscal Year: 2004
    ..Modulators of any of these newly identified steps may have therapeutic implications for individuals with high levels of CYP2E1. ..
  37. MyD118/CR6/GADD45 in Hematopoietic Homeostasis
    Dan Liebermann; Fiscal Year: 2005
    ....
  38. Inland Northwest Cancer Conference
    GARY MEADOWS; Fiscal Year: 2004
    ..The 2004 conference entitled "Bridging the Gap, Breakthroughs in Cancer Care and Research" will be held on November 12th and 13th at the Davenport Hotel in Spokane, WA. ..
  39. Host defense functions of M. tuberculosis lipoglycan
    Edward Chan; Fiscal Year: 2005
    ..3. To elucidate the role of the TLRs, MAPK and NFkB signaling pathways, and ManLAM in controlling the growth of M. tuberculosis in mouse and human macrophages and to correlate effects on growth with NO* and TNFa expression. ..
  40. MECHANISM OF THYMIC ATROPHY INDUCED BY ALCOHOL
    GARY MEADOWS; Fiscal Year: 2006
    ..The long term objective of this research is to understand the mechanism underlying the loss in thymic cellularity induced by high alcohol consumption and to determine the reversibility of this effect. ..
  41. Modulation by SAMe of CYP2E1-dependent Effects in Liver.
    Arthur Cederbaum; Fiscal Year: 2006
    ....
  42. ALCOHOL AND PYRAZOLE REACTION AND METABOLISM BY CYP2E1
    Arthur Cederbaum; Fiscal Year: 2006
    ..It is hoped that such studies in hepatocyte and HepG2 cell culture models and in-vivo models, will help to define further the biochemical and toxicological actions of CYP2E1 and its role in alcohol-induced liver injury. ..
  43. Arsenite Effects on CD40 Signaling and B-Cell Apoptosis
    DONNA MUSCARELLA; Fiscal Year: 2008
    ..abstract_text> ..
  44. 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. ..
  45. DNA damage signaling in oxygen toxicity in lung cells
    KUMUDA DAS; Fiscal Year: 2007
    ..Using these molecular approaches, we will define the mechanisms of DNA damage signaling n hyperoxia, which will significantly improve our understanding of pulmonary oxygen toxicity in lung cells [unreadable] [unreadable]..
  46. 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]..
  47. Anticarcinogenic Mechanisms of Tea Constituents
    Zigang Dong; Fiscal Year: 2007
    ....
  48. Effects of ethanol and CYP2E1 on liver function
    Arthur Cederbaum; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  49. LRRK2 and cellular pathways of Parkinson's Disease
    Wanli Smith; Fiscal Year: 2007
    ....
  50. Regulation of Mixed Lineage Kinase 3 by the tumor suppressor protein Merlin
    DEBORAH CHADEE; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  51. MECHANISMS OF DIETARY MODULATION OF MELANOMA INVASION
    GARY MEADOWS; Fiscal Year: 2003
    ..abstract_text> ..
  52. Lung Cancer Chemoprevention using Deguelin
    Ho Young Lee; Fiscal Year: 2008
    ..abstract_text> ..