Genomes and Genes
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
Publications270 found, 100 shown here
- 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 cellsA 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...
- Activation of JNK3 alpha 1 requires both MKK4 and MKK7: kinetic characterization of in vitro phosphorylated JNK3 alpha 1J 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...
- Tobacco smoke control of mucin production in lung cells requires oxygen radicals AP-1 and JNKErin 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...
- Activation of DNA methyltransferase 1 by EBV LMP1 Involves c-Jun NH(2)-terminal kinase signalingChia 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...
- The role of JNK and p38 MAPK activities in UVA-induced signaling pathways leading to AP-1 activation and c-Fos expressionAmy 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...
- Activation of MEK-1 and SEK-1 by Tpl-2 proto-oncoprotein, a novel MAP kinase kinase kinaseA 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...
- 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 inductionElizabeth K Brint
Cytokine Research Group, Department of Biochemistry, Trinity College, Dublin 2, Ireland
J Biol Chem 277:49205-11. 2002....
- TAB1beta (transforming growth factor-beta-activated protein kinase 1-binding protein 1beta ), a novel splicing variant of TAB1 that interacts with p38alpha but not TAK1Baoxue Ge
Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA
J Biol Chem 278:2286-93. 2003....
- Phosphorylation and inactivation of myeloid cell leukemia 1 by JNK in response to oxidative stressSeiji 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...
- 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 assocT 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...
- Ser/Thr protein phosphatase 5 inactivates hypoxia-induced activation of an apoptosis signal-regulating kinase 1/MKK-4/JNK signaling cascadeGuofei 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 (..
- Independent human MAP-kinase signal transduction pathways defined by MEK and MKK isoformsB 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...
- Human mitogen-activated protein kinase kinase 4 as a candidate tumor suppressorD 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-..
- Alterations in pancreatic, biliary, and breast carcinomas support MKK4 as a genetically targeted tumor suppressor geneG H Su
Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205 2196, USA
Cancer Res 58:2339-42. 1998Mitogen-activated protein kinase (MAPK) kinase 4 (MKK4) is a component of a stress and cytokine-induced signal transduction pathway involving MAPK proteins...
- JSAP1, a novel jun N-terminal protein kinase (JNK)-binding protein that functions as a Scaffold factor in the JNK signaling pathwayM 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...
- 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 MKK7Y 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 ..
- Mitogen-activated protein kinase kinase 4 metastasis suppressor gene expression is inversely related to histological pattern in advancing human prostatic cancersH 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...
- Akt (protein kinase B) negatively regulates SEK1 by means of protein phosphorylationHee 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...
- Cardiac-specific deletion of mkk4 reveals its role in pathological hypertrophic remodeling but not in physiological cardiac growthWei 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...
- MEK4 function, genistein treatment, and invasion of human prostate cancer cellsLi 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...
- Functional and clinicopathological analysis of loss of MKK4 expression in endometrial cancerMasako Ishikawa
Department of Obstetrics and Gynecology, Shimane University School of Medicine, Izumo, Japan
Oncology 79:238-46. 2010In the current study, we investigated the mechanism relating downregulation of mitogen-activated protein kinase kinase-4 (MKK4) expression to the development of endometrial cancer.
- MKK4 acts as a potential tumor suppressor in ovarian cancerShamima Yeasmin
Department of Obstetrics and Gynecology, Shimane University School of Medicine, Enyacho 89 1, Izumo, Shimane, 6938501, Japan
Tumour Biol 32:661-70. 2011Our 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...
- MEKK1 binds raf-1 and the ERK2 cascade componentsM 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...
- 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...
- Homozygous deletion of MKK4 in ovarian serous carcinomaKentaro 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)...
- Proteomic analysis of GTP cyclohydrolase 1 multiprotein complexes in cultured normal adult human astrocytes under both basal and cytokine-activated conditionsAnna 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...
- 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 diseaseYue 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...
- Phosphorylation-dependent scaffolding role of JSAP1/JIP3 in the ASK1-JNK signaling pathway. A new mode of regulation of the MAP kinase cascadeHiroshi 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...
- Gene transfer of the JNK interacting protein-1 protects dopaminergic neurons in the MPTP model of Parkinson's diseaseX 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...
- Neuroprotection of ethanol against ischemia/reperfusion-induced brain injury through decreasing c-Jun N-terminal kinase 3 (JNK3) activation by enhancing GABA releaseS 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...
- Impaired CD28-mediated interleukin 2 production and proliferation in stress kinase SAPK/ERK1 kinase (SEK1)/mitogen-activated protein kinase kinase 4 (MKK4)-deficient T lymphocytesH 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. 1997The 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, ..
- Vaccination alone or in combination with pyridostigmine promotes and prolongs activation of stress-activated kinases induced by stress in the mouse brainDechun 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)...
- 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-regulationTamara 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...
- 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 ratsRan 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 ..
- Phloroglucinol (1,3,5-trihydroxybenzene) protects against ionizing radiation-induced cell damage through inhibition of oxidative stress in vitro and in vivoKyoung 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...
- Astrocyte protection of neurons: role of transforming growth factor-beta signaling via a c-Jun-AP-1 protective pathwayKrishnan 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...
- Eicosapentaenoic acid inhibits UV-induced MMP-1 expression in human dermal fibroblastsHyeon 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...
- Identification of small-molecule inhibitors of the JIP-JNK interactionTracy 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)...
- Dual roles for c-Jun N-terminal kinase in developmental and stress responses in cerebellar granule neuronsE 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...
- c-Jun NH2-terminal kinase-related Na+/H+ exchanger isoform 1 activation controls hexokinase II expression in benzo(a)pyrene-induced apoptosisLaurence 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...
- Mitogen-activated protein kinase kinase 7 is activated during low potassium-induced apoptosis in rat cerebellar granule neuronsLinda 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)...
- Specific amino acid deficiency alters the expression of genes in human melanoma and other tumor cell linesG 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...
- Expression and mutation analyses of MKK4, a candidate tumour suppressor gene encoded by chromosome 17p, in human gastric adenocarcinomaK S Chae
Department of Pathology, College of Medicine, Kyung Hee University, Seoul 130 701, South Korea
Eur J Cancer 38:2048-57. 2002Homozygous 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...
- Loss of MKK4 expression in ovarian cancer: a potential role for the epithelial to mesenchymal transitionShamima 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...
- A functional variant (-1304T>G) in the MKK4 promoter contributes to a decreased risk of lung cancer by increasing the promoter activityBin Liu
The Institute for Chemical Carcinogenesis, Guangzhou Medical College, People s Republic of China
Carcinogenesis 31:1405-11. 2010Mitogen-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...
- Role of mitogen-activated protein kinase kinase 4 in cancerA J Whitmarsh
Faculty of Life Sciences, University of Manchester, Manchester, UK
Oncogene 26:3172-84. 2007Mitogen-activated protein (MAP) kinase kinase 4 (MKK4) is a component of stress activated MAP kinase signaling modules...
- Targeted deletion of the mitogen-activated protein kinase kinase 4 gene in the nervous system causes severe brain developmental defects and premature deathXin 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...
- Increased expression of IRE1alpha and stress-related signal transduction proteins in ischemia-reperfusion injured retinaNatsuyo 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 ..
- The mitogen-activated protein kinase kinase 4 has a pro-oncogenic role in skin cancerKatherine G Finegan
Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester, United Kingdom
Cancer Res 70:5797-806. 2010The mitogen-activated protein kinase (MAPK) kinase 4 (MKK4) is a nonredundant component of stress-activated MAPK signaling modules...
- 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 stimuliI 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...
- Role of the stress-activated protein kinases in endothelin-induced cardiomyocyte hypertrophyG Choukroun
Renal Unit, and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA
J Clin Invest 102:1311-20. 1998....
- A novel mechanism of JNK1 activation. Nuclear translocation and activation of JNK1 during ischemia and reperfusionY 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 ..
- Cocoa procyanidins attenuate 4-hydroxynonenal-induced apoptosis of PC12 cells by directly inhibiting mitogen-activated protein kinase kinase 4 activityEun 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...
- Isolation of MEK5 and differential expression of alternatively spliced formsJ 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 ..
- Signal transduction of nitric oxide donor-induced protection in hydrogen peroxide-mediated apoptosis in H9C2 cardiomyoblastsH 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...
- A human homolog of the yeast Ssk2/Ssk22 MAP kinase kinase kinases, MTK1, mediates stress-induced activation of the p38 and JNK pathwaysM 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...
- The Parkinson disease-associated protein kinase LRRK2 exhibits MAPKKK activity and phosphorylates MKK3/6 and MKK4/7, in vitroChristian 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...
- 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 cellsK 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 ..
- A novel SAPK/JNK kinase, MKK7, stimulated by TNFalpha and cellular stressesT 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...
- Selective activation and functional significance of p38alpha mitogen-activated protein kinase in lipopolysaccharide-stimulated neutrophilsJ 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 ..
- The MLK family mediates c-Jun N-terminal kinase activation in neuronal apoptosisZ 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...
- 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 kinasesAe 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 ..
- Regulation of the JNK pathway by TGF-beta activated kinase 1 in rheumatoid arthritis synoviocytesDeepa 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)...
- A non-redundant role for Drosophila Mkk4 and hemipterous/Mkk7 in TAK1-mediated activation of JNKPeter 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...
- Activation of ASK1, downstream MAPKK and MAPK isoforms during cardiac ischaemiaStephen 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 ..
- The MKK7 gene encodes a group of c-Jun NH2-terminal kinase kinasesC 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...
- Stress- and cell type-dependent regulation of transfected c-Jun N-terminal kinase and mitogen-activated protein kinase kinase isoformsL 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...
- Ebselen inhibits tumor necrosis factor-alpha-induced c-Jun N-terminal kinase activation and adhesion molecule expression in endothelial cellsMasanori 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...
- Diverse physiological functions of MKK4 and MKK7 during early embryogenesisYoichi 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...
- Surviving the passage: Non-canonical stromal targeting of an Arabidopsis mitogen-activated protein kinase kinaseMarcus 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 ..
- Delphinidin suppresses ultraviolet B-induced cyclooxygenases-2 expression through inhibition of MAPKK4 and PI-3 kinaseJung 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...
- Novel and expanded roles for MAPK signaling in Arabidopsis stomatal cell fate revealed by cell type-specific manipulationsGregory 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...
- Activation of Erk and JNK MAPK pathways by acute swim stress in rat brain regionsChang 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...
- 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 cancerHo 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...
- Direct activation of mitochondrial apoptosis machinery by c-Jun N-terminal kinase in adult cardiac myocytesHiroki 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 ..
- PP2A regulates upstream members of the c-jun N-terminal kinase mitogen-activated protein kinase signaling pathwayBin 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...
- Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathwaysH 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 ..
- 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 vivoK 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...
- 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-1A 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)...
- Expression of mixed lineage kinase 2 in germ cells of the testisD 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 ..
- Beta-arrestin 2: a receptor-regulated MAPK scaffold for the activation of JNK3P 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...
- Susceptibility of mitogen-activated protein kinase kinase family members to proteolysis by anthrax lethal factorG 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...
- Involvement of alpha-PAK-interacting exchange factor in the PAK1-c-Jun NH(2)-terminal kinase 1 activation and apoptosis induced by benzo[a]pyreneS 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...
- Prevention of kidney ischemia/reperfusion-induced functional injury, MAPK and MAPK kinase activation, and inflammation by remote transient ureteral obstructionKwon 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...
- 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 recepKoichi 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...
- Activation mechanism of c-Jun amino-terminal kinase in the course of endodermal differentiation of P19 embryonic carcinoma cellsTada 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...
- Role of the ASK1-SEK1-JNK1-HIPK1 signal in Daxx trafficking and ASK1 oligomerizationJae 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...
- Resveratrol inhibits phorbol myristate acetate-induced matrix metalloproteinase-9 expression by inhibiting JNK and PKC delta signal transductionJu 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...
- Protein kinase R (PKR) interacts with and activates mitogen-activated protein kinase kinase 6 (MKK6) in response to double-stranded RNA stimulationAristobolo 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...
- Negative regulation of MEKK1-induced signaling by glutathione S-transferase MuKanghyun 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...
- Requirement of MKK4 and MKK7 for CdCl2- or HgCl2-induced activation of c-Jun NH2-terminal kinase in mouse embryonic stem cellsMasato 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)...
- G alpha 13 signals via p115RhoGEF cascades regulating JNK1 and primitive endoderm formationYi 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...
- Mitogen-activated protein kinases and mitogen-activated protein kinase phosphatases mediate the inhibitory effects of all-trans retinoic acid on the hypertrophic growth of cardiomyocytesAnts 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...
- DNA damage in transcribed genes induces apoptosis via the JNK pathway and the JNK-phosphatase MKP-1Mohamed 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...
- 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)...
- Transcriptional regulation of human CC chemokine CCL15 gene by NF-kappaB and AP-1 elements in PMA-stimulated U937 monocytoid cellsYong 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...
- Varicella-zoster virus infection of human fibroblast cells activates the c-Jun N-terminal kinase pathwayHeidi 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...
- Structural polymorphism of chromodomains in Chd1Masahiko 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...
- Stomatal development and patterning are regulated by environmentally responsive mitogen-activated protein kinases in ArabidopsisHuachun 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...
- Post-transcriptional regulation of human inducible nitric-oxide synthase expression by the Jun N-terminal kinaseRiku 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...
- Microarray analysis of oxidative stress regulated genes in mesencephalic dopaminergic neuronal cells: relevance to oxidative damage in Parkinson's diseaseVellareddy 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...
- Jonathan M Kurie; Fiscal Year: 2016..metastasis is MAP2K4, which encodes the stress- and cytokine-regulated mitogen activated protein kinase kinase-4 (MKK4)...
- 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...
- c-Jun N-terminal kinase and joint destruction in RAGary S Firestein; Fiscal Year: 2012..Two upstream kinases, MKK4 and MKK7, can independently activate JNK and initiate protease and cytokine gene expression...
- Bioflavonoid Effects on EGF Signaling and Cell Cycle Pathways in Prostate CancerBARRY 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)...
- REGULATION OF A C JUN KINASE BY A NOVEL TUMOR PROMOTERELIZABETH 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...
- 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...
- p38 MAPK as a therapeutic target in Myelodysplastic syndromeAmit 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...
- Molecular Inhibitors of Prostate Cancer MetastasisREBECCA 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...
- Prostate Cancer Metastatic Colonization: Role of MKK4Carrie 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...
- Interaction of anti-angiogenic and cytotoxic therapies in colorectal cancerPETER 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...
- 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...
- Signaling Complexes in Renal Epithelial CellsRichard 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 ..
- PROTEIN TYROSINE KINASES AND MAST CELL ACTIVATIONToshiaki 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 ..
- PATHOPHYSIOLOGY OF RENAL TUBULAR CELLSFrank Lee; Fiscal Year: 2002..Finally, MEKK1 can also activate the MAP2K MKK4 which, in turn, activates the stress induced kinase JNK...
- APOPTOSIS & CELL CYCLE IN BREAST & OVARIAN CANCER CELLSJay 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...
- LPS-INDUCED NEUTROPHIL ACCUMULATION IN THE LUNGG 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 ..
- HPK1-Mediated Lymphocyte Signal Transduction MechanismsTse Hua Tan; Fiscal Year: 2005..Receptors -> adaptors, kinases -> HPK1 (also called MAP4K1) -> MAP3Ks (MEKK1, TAK1, MLK3) -> MAP2Ks (MKK4, MKKT) !->JNK -> cell activation or apoptosis...
- HPK1 MEDIATED T CELL SIGNAL TRANSDUCTION MECHANISMSTse 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...
- MOLECULAR MECHANISMS OF TNF ALPHA INDUCED CYTOTOXICITYAnning 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-..
- APOPTOSIS IN PROSTATE CANCEREdward Gelmann; Fiscal Year: 2001..The dominant negative constructs will block RB interaction with ABL, ABL kinase, CAP kinase, SEK1 kinase and JUN.
- MLK3 function in neurofibromatosis tumor cellsJohn 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. ..
- Induction of immunological paralysis by CpG DNAAe Kyung Yi; Fiscal Year: 2008..abstract_text> ..
- Mechanisms of chemopreventive effect of resveratrolZigang 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. ..
- NEGATIVE REGULATORS OF MYELOPOIESISBarbara Hoffman; Fiscal Year: 2009..This knowledge should provide novel tools for designing drugs to promote differentiation and/or apoptosis of leukemic cells. ..
- INHIBITION OF CARCINOGENESIS BY TEA AND TEA CONSTITUENTSZigang Dong; Fiscal Year: 2010..abstract_text> ..
- Gadd 45 in the Response of Hematopoietic Cells to StressDan A Liebermann; Fiscal Year: 2010....
- Study on Ultraviolet-induced Signal TransductionZigang Dong; Fiscal Year: 2010..These preclinical studies are designed to lead to the development of new strategies for the chemoprevention of human skin cancers. ..
- THE STRESS-ACTIVATED PROTEIN KINASE PATHWAYJohn M Kyriakis; Fiscal Year: 2010..These studies will provide important details of a previously unknown signaling pathway required for inflammatory responses. ..
- TARGETS OF AMINO ACID RESTRICTION IN PROSTATE CANCERGary 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. ..
- ROLE OF PKD IN LEUKOCYTE ACTIVATION BY CPG DNAAe 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. ..
- Mechanisms on metastasis and survival in alcoholic miceGary 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. ..
- MECHANISMS OF TGF BETA SIGNALINGKATHLEEN MULDER; Fiscal Year: 2001....
- ALCOHOL OXYGEN RADICAL INTERACTIONS AS DETECTED BY ESRArthur 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. ..
- Molecular basis of arsenic-induced cell transformationZigang 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. ..
- MyD118, CR6 and GADD45 in Genotoxic StressDan Liebermann; Fiscal Year: 2003....
- Degradation of Human CYP2E1 by the ProteasomeArthur Cederbaum; Fiscal Year: 2004..Modulators of any of these newly identified steps may have therapeutic implications for individuals with high levels of CYP2E1. ..
- MyD118/CR6/GADD45 in Hematopoietic HomeostasisDan Liebermann; Fiscal Year: 2005....
- Inland Northwest Cancer ConferenceGARY 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. ..
- Host defense functions of M. tuberculosis lipoglycanEdward 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. ..
- MECHANISM OF THYMIC ATROPHY INDUCED BY ALCOHOLGARY 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. ..
- Modulation by SAMe of CYP2E1-dependent Effects in Liver.Arthur Cederbaum; Fiscal Year: 2006....
- ALCOHOL AND PYRAZOLE REACTION AND METABOLISM BY CYP2E1Arthur 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. ..
- Arsenite Effects on CD40 Signaling and B-Cell ApoptosisDONNA MUSCARELLA; Fiscal Year: 2008..abstract_text> ..
- Cyclic GMP Phosphodiesterase in SignalingHsien 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. ..
- DNA damage signaling in oxygen toxicity in lung cellsKUMUDA 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]..
- Role of Km23 in Ovarian CancerKATHLEEN 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]..
- Anticarcinogenic Mechanisms of Tea ConstituentsZigang Dong; Fiscal Year: 2007....
- Effects of ethanol and CYP2E1 on liver functionArthur Cederbaum; Fiscal Year: 2007..unreadable] [unreadable] [unreadable] [unreadable]..
- LRRK2 and cellular pathways of Parkinson's DiseaseWanli Smith; Fiscal Year: 2007....
- Regulation of Mixed Lineage Kinase 3 by the tumor suppressor protein MerlinDEBORAH CHADEE; Fiscal Year: 2008..unreadable] [unreadable] [unreadable]..
- MECHANISMS OF DIETARY MODULATION OF MELANOMA INVASIONGARY MEADOWS; Fiscal Year: 2003..abstract_text> ..
- Lung Cancer Chemoprevention using DeguelinHo Young Lee; Fiscal Year: 2008..abstract_text> ..