map kinase kinase kinases

Summary

Summary: Mitogen-activated protein kinase kinase kinases (MAPKKKs) are serine-threonine protein kinases that initiate protein kinase signaling cascades. They phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES; (MAPKKs) which in turn phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs).

Top Publications

  1. ncbi The type I TGF-beta receptor engages TRAF6 to activate TAK1 in a receptor kinase-independent manner
    Alessandro Sorrentino
    Ludwig Institute for Cancer Research, Rudbeck Laboratory, Uppsala University, Sweden, Dag Hammarskjoldsv 20, SE 75185 Uppsala, Sweden
    Nat Cell Biol 10:1199-207. 2008
  2. pmc DLK initiates a transcriptional program that couples apoptotic and regenerative responses to axonal injury
    Trent A Watkins
    Neurodegeneration Laboratories, Department of Neuroscience, GENTECH, Inc, South San Francisco, CA 94080, USA
    Proc Natl Acad Sci U S A 110:4039-44. 2013
  3. pmc Dual leucine zipper kinase is required for retrograde injury signaling and axonal regeneration
    Jung Eun Shin
    Department of Developmental Biology, Washington University School of Medicine, St Louis, MO 63110, USA
    Neuron 74:1015-22. 2012
  4. pmc TAK1 negatively regulates NF-κB and p38 MAP kinase activation in Gr-1+CD11b+ neutrophils
    Adebusola Alagbala Ajibade
    Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030, USA
    Immunity 36:43-54. 2012
  5. ncbi TAK1 is a ubiquitin-dependent kinase of MKK and IKK
    C Wang
    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9148, USA
    Nature 412:346-51. 2001
  6. pmc TRAF6 mediates Smad-independent activation of JNK and p38 by TGF-beta
    Motozo Yamashita
    Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, MD 20892, USA
    Mol Cell 31:918-24. 2008
  7. 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
  8. pmc Direct activation of protein kinases by unanchored polyubiquitin chains
    Zong Ping Xia
    Department of Molecular Biology, University of Texas, Southwestern Medical Center, Dallas, Texas 75390 9148, USA
    Nature 461:114-9. 2009
  9. ncbi Essential function for the kinase TAK1 in innate and adaptive immune responses
    Shintaro Sato
    Akira Innate Immunity Project, Exploratory Research for Advanced Technology, Japan Science and Technology Agency
    Nat Immunol 6:1087-95. 2005
  10. ncbi TAB2 and TAB3 activate the NF-kappaB pathway through binding to polyubiquitin chains
    Atsuhiro Kanayama
    Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
    Mol Cell 15:535-48. 2004

Detail Information

Publications251 found, 100 shown here

  1. ncbi The type I TGF-beta receptor engages TRAF6 to activate TAK1 in a receptor kinase-independent manner
    Alessandro Sorrentino
    Ludwig Institute for Cancer Research, Rudbeck Laboratory, Uppsala University, Sweden, Dag Hammarskjoldsv 20, SE 75185 Uppsala, Sweden
    Nat Cell Biol 10:1199-207. 2008
    ..Our data show that TGF-beta specifically activates TAK1 through interaction of TbetaRI with TRAF6, whereas activation of Smad2 is not dependent on TRAF6...
  2. pmc DLK initiates a transcriptional program that couples apoptotic and regenerative responses to axonal injury
    Trent A Watkins
    Neurodegeneration Laboratories, Department of Neuroscience, GENTECH, Inc, South San Francisco, CA 94080, USA
    Proc Natl Acad Sci U S A 110:4039-44. 2013
    ..These findings demonstrate that these seemingly contradictory responses to injury are mechanistically coupled through a DLK-based damage detection mechanism...
  3. pmc Dual leucine zipper kinase is required for retrograde injury signaling and axonal regeneration
    Jung Eun Shin
    Department of Developmental Biology, Washington University School of Medicine, St Louis, MO 63110, USA
    Neuron 74:1015-22. 2012
    ..These data demonstrate that DLK enhances regeneration by promoting a retrograde injury signal that is required for the activation of the neuronal proregenerative program...
  4. pmc TAK1 negatively regulates NF-κB and p38 MAP kinase activation in Gr-1+CD11b+ neutrophils
    Adebusola Alagbala Ajibade
    Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030, USA
    Immunity 36:43-54. 2012
    ..Our findings identify a previously unrecognized role of TAK1 as a negative regulator of p38 and IKK activation in a cell type-specific manner...
  5. ncbi TAK1 is a ubiquitin-dependent kinase of MKK and IKK
    C Wang
    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9148, USA
    Nature 412:346-51. 2001
    ..We also provide evidence that TRAF6 is conjugated by the K63 polyubiquitin chains. These results indicate that ubiquitination has an important regulatory role in stress response pathways, including those of IKK and JNK...
  6. pmc TRAF6 mediates Smad-independent activation of JNK and p38 by TGF-beta
    Motozo Yamashita
    Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, MD 20892, USA
    Mol Cell 31:918-24. 2008
    ..Our results indicate that TGF-beta activates JNK and p38 through a mechanism similar to that operating in the interleukin-1beta/Toll-like receptor pathway...
  7. 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
    ....
  8. pmc Direct activation of protein kinases by unanchored polyubiquitin chains
    Zong Ping Xia
    Department of Molecular Biology, University of Texas, Southwestern Medical Center, Dallas, Texas 75390 9148, USA
    Nature 461:114-9. 2009
    ..These results indicate that unanchored polyubiquitin chains directly activate TAK1 and IKK, suggesting a new mechanism of protein kinase regulation...
  9. ncbi Essential function for the kinase TAK1 in innate and adaptive immune responses
    Shintaro Sato
    Akira Innate Immunity Project, Exploratory Research for Advanced Technology, Japan Science and Technology Agency
    Nat Immunol 6:1087-95. 2005
    ..However, TAK1-deficient B cells were able to activate NF-kappaB but not the kinase Jnk in response to B cell receptor stimulation. These results collectively indicate that TAK1 is key in the cellular response to a variety of stimuli...
  10. ncbi TAB2 and TAB3 activate the NF-kappaB pathway through binding to polyubiquitin chains
    Atsuhiro Kanayama
    Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
    Mol Cell 15:535-48. 2004
    ..These results indicate that polyubiquitin binding domains represent a new class of signaling domains that regulate protein kinase activity through a nonproteolytic mechanism...
  11. pmc TAK1 activates AMPK-dependent cytoprotective autophagy in TRAIL-treated epithelial cells
    Griselda Herrero-Martin
    Cell Signalling Department, Centro Andaluz de Biologia Molecular y Medicina Regenerativa CABIMER, Consejo Superior de Investigaciones Cientificas, Avenida Americo Vespucio s n, Sevilla, Spain
    EMBO J 28:677-85. 2009
    ....
  12. pmc TAK1, but not TAB1 or TAB2, plays an essential role in multiple signaling pathways in vivo
    Jae Hyuck Shim
    Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Genes Dev 19:2668-81. 2005
    ..Therefore, our studies suggests that TAK1 acts as an upstream activating kinase for IKKbeta and JNK, but not IKKalpha, revealing an unexpectedly specific role of TAK1 in inflammatory signaling pathways...
  13. ncbi A Mitogen-activated protein kinase kinase kinase mediates reactive oxygen species homeostasis in Arabidopsis
    Hirofumi Nakagami
    Department of Plant Molecular Biology, Max F Perutz Laboratories, University of Vienna, Dr Bohrgasse 9, A 1030 Vienna, Austria
    J Biol Chem 281:38697-704. 2006
    ..Overall, our data defines MPK4 as downstream target of MEKK1 and show that MEKK1 functions in integrating ROS homeostasis with plant development and hormone signaling...
  14. ncbi The TAK1-TRAF6 signalling pathway
    Marene Landström
    Rudbeck Laboratory, Department of Genetics and Pathology, Dag Hammarskjöld väg 20, Uppsala University, SE 751 24 Uppsala, Sweden
    Int J Biochem Cell Biol 42:585-9. 2010
    ..A handful of transcription factors are crucial for the determination of the specific cellular responses, where the transforming growth factor-beta (TGF-beta) is an important factor as discussed in this review...
  15. ncbi Mixed lineage kinase 3 (MLK3)-activated p38 MAP kinase mediates transforming growth factor-beta-induced apoptosis in hepatoma cells
    Ki Yong Kim
    Laboratory of Cell Regulation and Carcinogenesis, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 279:29478-84. 2004
    ..We also show that only the inhibition of the p38 pathway suppressed TGF-beta1-induced apoptosis. These observations support a role for MLKs in the TGF-beta1-induced cell death mechanism...
  16. ncbi Regulation of a DLK-1 and p38 MAP kinase pathway by the ubiquitin ligase RPM-1 is required for presynaptic development
    Katsunori Nakata
    Department of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, Santa Cruz, California 95064, USA
    Cell 120:407-20. 2005
    ..DLK-1 protein levels are elevated in rpm-1 mutants. The RPM-1 RING finger can stimulate ubiquitination of DLK-1. Our data reveal a presynaptic role of a previously unknown p38 MAP kinase cascade...
  17. pmc A critical role of RICK/RIP2 polyubiquitination in Nod-induced NF-kappaB activation
    Mizuho Hasegawa
    Department of Pathology, The University of Michigan Medical School, Ann Arbor, MI 48109, USA
    EMBO J 27:373-83. 2008
    ..Thus, RICK polyubiquitination links TAK1 to IKK complexes, a critical step in Nod1/Nod2-mediated NF-kappaB activation...
  18. ncbi A resorcylic acid lactone, 5Z-7-oxozeaenol, prevents inflammation by inhibiting the catalytic activity of TAK1 MAPK kinase kinase
    Jun Ninomiya-Tsuji
    Department of Molecular Biology, Graduate School of Science, Nagoya University, and CREST, Japan Science and Technology Corporation, Chikusa ku, Nagoya 464 8602, Japan
    J Biol Chem 278:18485-90. 2003
    ..Furthermore, in vivo 5Z-7-oxozeaenol was able to inhibit picryl chloride-induced ear swelling. Thus, 5Z-7-oxozeaenol blocks proinflammatory signaling by selectively inhibiting TAK1 MAPKKK...
  19. ncbi Imaging mass spectrometry of a specific fragment of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 2 discriminates cancer from uninvolved prostate tissue
    Lisa H Cazares
    Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, Virginia 23507, USA
    Clin Cancer Res 15:5541-51. 2009
    ..Direct profiling of proteins from tissue using matrix-assisted laser desorption/ionization imaging mass spectrometry has the potential to supplement morphology with underlying molecular detail...
  20. pmc Axon regeneration requires a conserved MAP kinase pathway
    Marc Hammarlund
    Department of Biology, University of Utah, 257 South 1400 East, Salt Lake City, UT 84112 0840, USA
    Science 323:802-6. 2009
    ..We conclude that after axon injury, activation of this MAP kinase cascade is required to switch the mature neuron from an aplastic state to a state capable of growth...
  21. pmc DLK induces developmental neuronal degeneration via selective regulation of proapoptotic JNK activity
    Arundhati Sengupta Ghosh
    Neurodegeneration Laboratories, Department of Neuroscience, Genentech, Inc, South San Francisco, CA 94080, USA
    J Cell Biol 194:751-64. 2011
    ..DLK-null mice displayed reduced apoptosis in multiple neuronal populations during development, demonstrating that prodegenerative DLK signaling is required in vivo...
  22. ncbi ASK1 is essential for JNK/SAPK activation by TRAF2
    H Nishitoh
    Department of Biochemistry, Cancer Institute, Tokyo, Japan
    Mol Cell 2:389-95. 1998
    ..In untransfected mammalian cells, ASK1 rapidly associates with TRAF2 in a TNF-dependent manner. Thus, ASK1 is a mediator of TRAF2-induced JNK activation...
  23. pmc Feedback control of the protein kinase TAK1 by SAPK2a/p38alpha
    Peter C F Cheung
    MRC Protein Phosphorylation Unit, School of Life Sciences, MSI WTB complex, Dow Street, University of Dundee, Dundee DD1 5EH, UK
    EMBO J 22:5793-805. 2003
    ....
  24. ncbi Identification of a member of the MAPKKK family as a potential mediator of TGF-beta signal transduction
    K Yamaguchi
    Department of Molecular Biology, Faculty of Science, Nagoya University, Japan
    Science 270:2008-11. 1995
    ..Furthermore, kinase activity of TAK1 was stimulated in response to TGF-beta and bone morphogenetic protein. These results suggest that TAK1 functions as a mediator in the signaling pathway of TGF-beta superfamily members...
  25. ncbi Smad7 binds to the adaptors TAB2 and TAB3 to block recruitment of the kinase TAK1 to the adaptor TRAF2
    Suntaek Hong
    Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892 50551, USA
    Nat Immunol 8:504-13. 2007
    ..Thus, Smad7 is a critical mediator of TGF-beta signals that block proinflammatory TNF signals...
  26. ncbi The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway
    J Ninomiya-Tsuji
    Department of Molecular Biology, Graduate School of Science, Nagoya University, and CREST, Japan Science and Technology Corporation
    Nature 398:252-6. 1999
    ..Activated TAK1 phosphorylates NIK, which stimulates IKK-alpha activity. Our results indicate that TAK1 links TRAF6 to the NIK-IKK cascade in the IL-1 signalling pathway...
  27. ncbi TNF-alpha induction by LPS is regulated posttranscriptionally via a Tpl2/ERK-dependent pathway
    C D Dumitru
    Kimmel Cancer Center, Department of Microbiology and Immunology, Thomas Jefferson University, 233 S 10th Street, Philadelphia, PA 19107, USA
    Cell 103:1071-83. 2000
    ..Subcellular fractionation of LPS-stimulated macrophages revealed that LPS signals transduced by Tpl2 specifically promote the transport of TNF-alpha mRNA from the nucleus to the cytoplasm...
  28. pmc The DLK-1 kinase promotes mRNA stability and local translation in C. elegans synapses and axon regeneration
    Dong Yan
    Division of Biological Sciences, Section of Neurobiology, University of California, San Diego, La Jolla, CA 92093, USA
    Cell 138:1005-18. 2009
    ..Our findings identify the DLK-1 pathway as a regulator of mRNA stability in synapse formation and maintenance and also in adult axon regeneration...
  29. ncbi TAK1 mitogen-activated protein kinase kinase kinase is activated by autophosphorylation within its activation loop
    K Kishimoto
    Department of Molecular Biology, Graduate School of Science, Nagoya University and CREST, Japan Science and Technology Corporation, Chikusa ku, Nagoya 464 8602, Japan
    J Biol Chem 275:7359-64. 2000
    ..These results suggest that IL-1 and ectopic expression of TAB1 both activate TAK1 via autophosphorylation of Ser-192...
  30. pmc Protein turnover of the Wallenda/DLK kinase regulates a retrograde response to axonal injury
    Xin Xiong
    Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA
    J Cell Biol 191:211-23. 2010
    ..Our data suggest that the regulation of Wnd protein turnover by Hiw can function as a damage surveillance mechanism for responding to axonal injury...
  31. pmc The E3 ligase Itch and deubiquitinase Cyld act together to regulate Tak1 and inflammation
    Neesar Ahmed
    Karmanos Cancer Institute, Department of Oncology, Wayne State University School of Medicine, Detroit, Michigan, USA
    Nat Immunol 12:1176-83. 2011
    ..Thus, we have identified an Itch-Cyld-mediated regulatory mechanism in innate inflammatory cells...
  32. pmc cIAP1 and TAK1 protect cells from TNF-induced necrosis by preventing RIP1/RIP3-dependent reactive oxygen species production
    N Vanlangenakker
    Department for Molecular Biomedical Research, VIB, Technologiepark 927, Zwijnaarde Ghent 9052, Belgium
    Cell Death Differ 18:656-65. 2011
    ..In conclusion, our data indicate that cIAP1 and TAK1 protect cells from TNF-induced necrosis by preventing RIP1/RIP3-dependent ROS production...
  33. pmc Ablation of TAK1 upregulates reactive oxygen species and selectively kills tumor cells
    Emily Omori
    Department of Environmental and Molecular Toxicology, North Carolina State University, Raleigh, North Carolina 27695 7633, USA
    Cancer Res 70:8417-25. 2010
    ..Normal skin did not exhibit any significant abnormality on tak1 gene deletion. Thus, TAK1 kinase could be a new and effective molecular target for ROS-based tumor killing...
  34. ncbi Targeting protein kinases for the development of anti-inflammatory drugs
    Philip Cohen
    The MRC Protein Phosphorylation Unit, University of Dundee, The Sir James Black Centre, Dundee, UK
    Curr Opin Cell Biol 21:317-24. 2009
    ....
  35. pmc TAK1 is required for the survival of hematopoietic cells and hepatocytes in mice
    Minghui Tang
    Oncology Institute, Cardinal Bernardin Cancer Center, Loyola University Medical Center, Maywood, IL 60153, USA
    J Exp Med 205:1611-9. 2008
    ..Deletion of TAK1 resulted in the inactivation of both JNK and NF-kappaB signaling, as well as the down-regulation of expression of prosurvival genes...
  36. pmc TGF-beta-activated kinase 1 signaling maintains intestinal integrity by preventing accumulation of reactive oxygen species in the intestinal epithelium
    Rie Kajino-Sakamoto
    Department of Environmental and Molecular Toxicology, North Carolina State University, Raleigh, NC 27695, USA
    J Immunol 185:4729-37. 2010
    ..Thus, TAK1 signaling regulates ROS through transcription factor NF-E2-related factor 2, which is important for intestinal epithelial integrity...
  37. ncbi Ubiquitin-mediated activation of TAK1 and IKK
    A Adhikari
    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390 9148, USA
    Oncogene 26:3214-26. 2007
    ..Recent biochemical and genetic studies provide further insights into the mechanism and function of ubiquitin signalling and these advances will be the focus of this review...
  38. ncbi TAK1 is critical for IkappaB kinase-mediated activation of the NF-kappaB pathway
    Giichi Takaesu
    Division of Hematology Oncology, Department of Medicine, Harold Simmons Cancer Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390 8594, USA
    J Mol Biol 326:105-15. 2003
    ..This analysis further defines the distinct in vivo roles of IKKalpha, IKKbeta and TAK1 in cytokine-induced activation of the NF-kappaB pathway...
  39. pmc A dual leucine kinase-dependent axon self-destruction program promotes Wallerian degeneration
    Bradley R Miller
    Department of Developmental Biology, Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis, Missouri, USA
    Nat Neurosci 12:387-9. 2009
    ..This pathway also promoted degeneration after chemotherapy exposure and may be a component of a general axon self-destruction program...
  40. pmc ABIN-2 forms a ternary complex with TPL-2 and NF-kappa B1 p105 and is essential for TPL-2 protein stability
    V Lang
    Division of Immune Cell Biology, National Institute for Medical Research, Mill Hill, London NW7 1AA, United Kingdom
    Mol Cell Biol 24:5235-48. 2004
    ..Thus, optimal TPL-2 stability in vivo requires interaction with ABIN-2 as well as p105. Together, these data raise the possibility that ABIN-2 functions in the TLR4 signaling pathway which regulates TPL-2 activation...
  41. pmc Phosphorylation and polyubiquitination of transforming growth factor beta-activated kinase 1 are necessary for activation of NF-kappaB by the Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor
    Virginie Bottero
    Department of Microbiology and Immunology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA
    J Virol 85:1980-93. 2011
    ..Finally, inhibition of TAK1 by celastrol inhibited vGPCR-induced NF-κB activation, indicating this natural compound could be used as a potential therapeutic drug against KSHV malignancies involving vGPCR...
  42. pmc Overload of the heat-shock protein H11/HspB8 triggers melanoma cell apoptosis through activation of transforming growth factor-beta-activated kinase 1
    B Li
    Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
    Oncogene 26:3521-31. 2007
    ..The data indicate that H11/HspB8 overload causes melanoma growth arrest and apoptosis through TAK1 activation and suggest that H11/HspB8 is a promising molecular therapy target...
  43. pmc Tpl2 kinase is upregulated in adipose tissue in obesity and may mediate interleukin-1beta and tumor necrosis factor-{alpha} effects on extracellular signal-regulated kinase activation and lipolysis
    Jennifer Jager
    Institut National de la Sante et de la Recherche Medicale INSERM, U895, Mediterranean Center of Molecular Medicine, Team 7 Molecular and Cellular Physiopathology of Obesity and Diabetes, Nice, France
    Diabetes 59:61-70. 2010
    ..This study aims at identifying proteins regulating ERK1/2 activity, specifically in response to inflammatory cytokines, to provide new insights into mechanisms leading to abnormal adipose tissue function...
  44. pmc The RA domain of Ste50 adaptor protein is required for delivery of Ste11 to the plasma membrane in the filamentous growth signaling pathway of the yeast Saccharomyces cerevisiae
    Dagmar M Truckses
    Department of Molecular and Cell Biology, Division of Biochemistry and Molecular Biology, University of California, Room 16, Barker Hall, Berkeley, CA 94720 3202, USA
    Mol Cell Biol 26:912-28. 2006
    ..Thus, Ste50 serves as an adaptor to tether Ste11 to the plasma membrane and can do so via association with Cdc42, thereby permitting the encounter of Ste11 with activated Ste20...
  45. ncbi Ste5 tethers multiple protein kinases in the MAP kinase cascade required for mating in S. cerevisiae
    K Y Choi
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115
    Cell 78:499-512. 1994
    ..Ste5 also increases the amount of Ste11 complexed to Ste7 and Fus3 and is required for Ste11 to function. These results substantiate a novel signal transduction component that physically links multiple kinases within a single cascade...
  46. pmc A pivotal role for endogenous TGF-beta-activated kinase-1 in the LKB1/AMP-activated protein kinase energy-sensor pathway
    Min Xie
    Center for Cardiovascular Development, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA
    Proc Natl Acad Sci U S A 103:17378-83. 2006
    ..Thus, by disrupting the endogenous TAK1 locus, we prove a pivotal role for TAK1 in the LKB1/AMPK signaling axis, an essential governor of cell metabolism...
  47. ncbi Therapeutic resistance resulting from mutations in Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR signaling pathways
    James A McCubrey
    Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, North Carolina 27858, USA
    J Cell Physiol 226:2762-81. 2011
    ..Controlling the expression of these pathways could improve cancer therapy and ameliorate human health...
  48. pmc The requirement for Phr1 in CNS axon tract formation reveals the corticostriatal boundary as a choice point for cortical axons
    A Joseph Bloom
    Department of Molecular Biology and Pharmacology, Washington University, Saint Louis, Missouri 63110, USA
    Genes Dev 21:2593-606. 2007
    ..Thus, in the mammalian nervous system Phr1 is required for formation of major CNS axon tracts via a mechanism that is both cell-nonautonomous and independent of DLK...
  49. pmc TAK1 regulates reactive oxygen species and cell death in keratinocytes, which is essential for skin integrity
    Emily Omori
    Department of Environmental and Molecular Toxicology, North Carolina State University, Raleigh, North Carolina 27695 7633, USA
    J Biol Chem 283:26161-8. 2008
    ..Thus, TAK1 regulates ROS partially through c-Jun, which is important for preventing ROS-induced skin inflammation...
  50. pmc MAPKKKalpha is a positive regulator of cell death associated with both plant immunity and disease
    Olga del Pozo
    Boyce Thompson Institute for Plant Research, Ithaca, NY, USA
    EMBO J 23:3072-82. 2004
    ..These results demonstrate that signal transduction pathways associated with both plant immunity and disease susceptibility share a common molecular switch...
  51. ncbi TAK1 suppresses a NEMO-dependent but NF-kappaB-independent pathway to liver cancer
    Kira Bettermann
    Department of Internal Medicine III, University Hospital RWTH Aachen, D 52074 Aachen, Germany
    Cancer Cell 17:481-96. 2010
    ..Therefore, TAK1 serves as a gatekeeper for a protumorigenic, NF-kappaB-independent function of NEMO in parenchymal liver cells...
  52. pmc Wnt-1 signal induces phosphorylation and degradation of c-Myb protein via TAK1, HIPK2, and NLK
    Chie Kanei-Ishii
    Laboratory of Molecular Genetics, RIKEN Tsukuba Institute, Tsukuba, Ibaraki 305 0074, Japan
    Genes Dev 18:816-29. 2004
    ..The down-regulation of Myb by Wnt-1 signal may play an important role in a variety of developmental steps...
  53. pmc Targeting of TAK1 by the NF-kappa B protein Relish regulates the JNK-mediated immune response in Drosophila
    Jin Mo Park
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, 92093 0636, USA
    Genes Dev 18:584-94. 2004
    ..Because the IKK-NF-kappa B module also negatively regulates JNK activation in mammals, thereby controlling inflammation-induced apoptosis, the regulatory cross-talk between the JNK and NF-kappa B pathways appears to be broadly conserved...
  54. pmc Enterocyte-derived TAK1 signaling prevents epithelium apoptosis and the development of ileitis and colitis
    Rie Kajino-Sakamoto
    Department of Environmental and Molecular Toxicology, North Carolina State University, Raleigh, NC 27695, USA
    J Immunol 181:1143-52. 2008
    ..We propose that aberration in TAK1 signaling might disrupt intestinal homeostasis and favor the development of inflammatory disease...
  55. pmc Autoactivation of transforming growth factor beta-activated kinase 1 is a sequential bimolecular process
    Roland Scholz
    Department of Biology, Institute of Cell Biology, ETH Zurich, 8093 Zurich, Switzerland
    J Biol Chem 285:25753-66. 2010
    ..Finally, we present a model for the chronological order of events governing TAB1-induced TAK1 autoactivation...
  56. ncbi The TGF beta activated kinase TAK1 regulates vascular development in vivo
    Joy L Jadrich
    Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455, USA
    Development 133:1529-41. 2006
    ....
  57. pmc Activation of the yeast SSK2 MAP kinase kinase kinase by the SSK1 two-component response regulator
    F Posas
    Dana Farber Cancer Institute and Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    EMBO J 17:1385-94. 1998
    ..In the second step, autophosphorylation of SSK2 renders its activity independent of the presence of SSK1. A similar mechanism might be applicable to other MAPKKKs from both yeast and higher eukaryotes...
  58. ncbi Stomatal development and pattern controlled by a MAPKK kinase
    Dominique C Bergmann
    Carnegie Institution, Department of Plant Biology, Stanford University, Stanford, CA 94305, USA
    Science 304:1494-7. 2004
    ..A putative transcription factor from this set was shown to regulate the developmental behavior of stomatal precursors...
  59. ncbi TAB2, a novel adaptor protein, mediates activation of TAK1 MAPKKK by linking TAK1 to TRAF6 in the IL-1 signal transduction pathway
    G Takaesu
    Department of Molecular Biology, Graduate School of Science, Nagoya University and CREST, Japan
    Mol Cell 5:649-58. 2000
    ..These results define TAB2 as an adaptor linking TAK1 and TRAF6 and as a mediator of TAK1 activation in the IL-1 signaling pathway...
  60. ncbi Phosphorylation-dependent activation of TAK1 mitogen-activated protein kinase kinase kinase by TAB1
    H Sakurai
    Discovery Research Laboratory, Tanabe Seiyaku Co, Ltd, 16 89 Kashima 3 chome, Yodogawa ku, 532 8505, Osaka, Japan
    FEBS Lett 474:141-5. 2000
    ..These results demonstrated that the association between the kinase domain of TAK1 and the C-terminal TAB1 triggered the phosphorylation-dependent TAK1 activation mechanism...
  61. pmc Lysine 63-linked polyubiquitination of TAK1 at lysine 158 is required for tumor necrosis factor alpha- and interleukin-1beta-induced IKK/NF-kappaB and JNK/AP-1 activation
    Yihui Fan
    Laboratory of Medical Genetics, Harbin Medical University, Harbin 150081, China
    J Biol Chem 285:5347-60. 2010
    ....
  62. ncbi Tissue distribution and functional expression of a cDNA encoding a novel mixed lineage kinase
    L J Bloem
    Cardiovascular Discovery Research, Eli Lilly and Company, Indianapolis, IN 46285, USA
    J Mol Cell Cardiol 33:1739-50. 2001
    ..These data suggest that MLK7 is a new member of the mixed lineage kinase family that modulates cardiac SAPK/JNK pathway and may play a role in cardiac hypertrophy and progression to heart failure...
  63. pmc STAT3 regulates Nemo-like kinase by mediating its interaction with IL-6-stimulated TGFbeta-activated kinase 1 for STAT3 Ser-727 phosphorylation
    Hirotada Kojima
    Department of Immunology, Osaka City University Graduate School of Medicine, 1 4 3 Asahi machi, Abeno Ku, Osaka 545 8585, Japan
    Proc Natl Acad Sci U S A 102:4524-9. 2005
    ..Together, these results indicate that STAT3 enhances the efficiency of its own Ser-727 phosphorylation by acting as a scaffold for the TAK1-NLK kinases, specifically in the YXXQ motif-derived pathway...
  64. pmc Negative feedback regulation of ASK1 by protein phosphatase 5 (PP5) in response to oxidative stress
    K Morita
    Cell Signaling, Graduate School, Tokyo Medical and Dental University, 1 5 45 Yushima, Bunkyo ku, Tokyo 113 8549, Japan
    EMBO J 20:6028-36. 2001
    ..PP5 inhibited not only H(2)O(2)-induced sustained activation of ASK1 but also ASK1-dependent apoptosis. Thus, PP5 appears to act as a physiological inhibitor of ASK1-JNK/p38 pathways by negative feedback...
  65. ncbi Ras participates in the activation of p38 MAPK by interleukin-1 by associating with IRAK, IRAK2, TRAF6, and TAK-1
    Eva Pålsson McDermott
    Department of Biochemistry and Biotechnology Institute, Trinity College, Dublin 2, Ireland
    J Biol Chem 277:7808-15. 2002
    ..Our study suggests that upon activation Ras becomes associated with IRAK, Traf-6, and TAK-1, possibly aiding the assembly of this multiprotein signaling complex required for p38 MAPK activation by IL-1...
  66. ncbi Stimulus-specific requirements for MAP3 kinases in activating the JNK pathway
    Wei Chen
    Departments of Pharmacology and Cell Biology and Neuroscience, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390 9041, USA
    J Biol Chem 277:49105-10. 2002
    ..On the other hand, sorbitol requires expression of four MAP3Ks to cause maximal JNK activation. Thus, we demonstrate that specific stimuli use different mechanisms to recruit distinct MAP3Ks to regulate the JNK pathway...
  67. ncbi Reactive oxygen species- and dimerization-induced activation of apoptosis signal-regulating kinase 1 in tumor necrosis factor-alpha signal transduction
    Y Gotoh
    Fred Hutchinson Cancer Research Center, A2 025, Seattle, Washington 98109, USA
    J Biol Chem 273:17477-82. 1998
    ..These results taken together suggest that TNFalpha causes ASK1 activation via ROS-mediated dimerization of ASK1...
  68. pmc Regulation of DLK-1 kinase activity by calcium-mediated dissociation from an inhibitory isoform
    Dong Yan
    Neurobiology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA
    Neuron 76:534-48. 2012
    ..The DLK activation mechanism is ideally suited for rapid and spatially controlled signal transduction in response to axonal injury and synaptic activity...
  69. pmc Identification of three MAPKKKs forming a linear signaling pathway leading to programmed cell death in Nicotiana benthamiana
    Masayoshi Hashimoto
    Department of Agricultural and Environmental Biology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1 1 1 Yayoi, Bunkyo ku, Tokyo, 113 8657, Japan
    BMC Plant Biol 12:103. 2012
    ..Here, we performed a comparative functional analysis of MAPKKKs to investigate the signaling pathway leading to the defense response...
  70. pmc Coordinate regulation of TPL-2 and NF-κB signaling in macrophages by NF-κB1 p105
    Huei Ting Yang
    Division of Immune Cell Biology, MRC National Institute for Medical Research, Mill Hill, London, United Kingdom
    Mol Cell Biol 32:3438-51. 2012
    ..Unexpectedly, TPL-2 promoted soluble TNF production independently of IKK-induced p105 phosphorylation and its ability to activate ERK, which has important implications for the development of anti-inflammatory drugs targeting TPL-2...
  71. pmc Mixed lineage kinase 3 is required for matrix metalloproteinase expression and invasion in ovarian cancer cells
    Yu Zhan
    Department of Biological Sciences, The University of Toledo, Toledo, OH 43606, USA
    Exp Cell Res 318:1641-8. 2012
    ..In addition, inhibition of activator protein-1 (AP-1) reduced MMP-1, MMP-9 and MMP-12 gene expression. Collectively, these findings establish MLK3 as an important regulator of MMP expression and invasion in ovarian cancer cells...
  72. pmc Suppression of Tak1 promotes prostate tumorigenesis
    Min Wu
    Department of Cancer Biology, Wake Forest University School of Medicine, Winston Salem, North Carolina, USA
    Cancer Res 72:2833-43. 2012
    ..Together, our findings functionally validate the proposed tumor suppressor role of Tak1 in prostate cancer...
  73. ncbi TAK1 plays a major role in growth factor-induced phenotypic modulation of airway smooth muscle
    Tonio Pera
    Department of Molecular Pharmacology, University Centre for Pharmacy, University of Groningen, Groningen, The Netherlands
    Am J Physiol Lung Cell Mol Physiol 301:L822-8. 2011
    ..In addition, LL-Z-1640-2 inhibited PDGF-induced reduction of BTSM contractility and smooth muscle α-actin expression. The data indicate that TAK1 plays a major role in growth factor-induced phenotypic modulation of ASM...
  74. pmc TAK1 Lys-158 but not Lys-209 is required for IL-1β-induced Lys63-linked TAK1 polyubiquitination and IKK/NF-κB activation
    Yihui Fan
    Texas Children s Cancer Center, Department of Pediatrics, Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, United States
    Cell Signal 23:660-5. 2011
    ..Reconstitution of TAK1-deficient mouse embryo fibroblast cells with wild-type, K158R mutant, or K209R mutant TAK1 reveals that TAK1 Lys-158 but not Lys-209 is required for IL-1β-induced IKK, p38 and JNK activation...
  75. pmc JNK-mediated phosphorylation of DLK suppresses its ubiquitination to promote neuronal apoptosis
    Sarah Huntwork-Rodriguez
    Department of Neuroscience, 2 Department of Microchemical Proteomics, and 3 Department of Physiological Chemistry, Genentech, Inc, South San Francisco, CA 94080, USA
    J Cell Biol 202:747-63. 2013
    ..Through this feedback mechanism, the ubiquitin-proteasome system is able to provide an additional layer of regulation of retrograde stress signaling to generate a global cellular response to localized external insults. ..
  76. ncbi MAPK-upstream protein kinase (MUK) regulates the radial migration of immature neurons in telencephalon of mouse embryo
    Syu ichi Hirai
    Department of Molecular Biology, Yokohama City University School of Medicine, 3 9 Fukuura, Kanazawa Ku, Yokohama 236 0004, Japan
    Development 129:4483-95. 2002
    ..In COS-1 cells, MUK/DLK/ZPK overexpression impairs the radial organization of microtubules without massive depolymerization. These results suggest that MUK/DLK/ZPK and JNK regulate radial cell migration via microtubule-based events...
  77. pmc Tumor progression locus 2 (TPL2) regulates obesity-associated inflammation and insulin resistance
    James W Perfield
    Obesity and Metabolism Laboratory, JM USDA Human Nutrition esearch Center on Aging, Tufts University, Boston, Massachusetts, USA
    Diabetes 60:1168-76. 2011
    ..We used TPL2 knockout (KO) mice to investigate the role of TPL2 in mediating obesity-associated inflammation and insulin resistance...
  78. pmc HINKEL kinesin, ANP MAPKKKs and MKK6/ANQ MAPKK, which phosphorylates and activates MPK4 MAPK, constitute a pathway that is required for cytokinesis in Arabidopsis thaliana
    Yuji Takahashi
    Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa ku, Nagoya 464 8602, Japan
    Plant Cell Physiol 51:1766-76. 2010
    ..Although HINKEL/AtNACK1 (HIK) KLP, ANP MAP kinase kinase kinases (MAPKKKs) and MKK6/ ANQ MAP kinase kinase (MAPKK) have been identified independently as regulators of ..
  79. pmc TAK1 regulates cartilage and joint development via the MAPK and BMP signaling pathways
    Lea M Gunnell
    Department of Orthopaedics and Rehabilitation, Center for Musculoskeletal Research, University of Rochester, Rochester, NY, USA
    J Bone Miner Res 25:1784-97. 2010
    ..Taken together, these data demonstrate that TAK1 is a critical regulator of both MAPK and BMP signaling and is necessary for proper cartilage and joint development...
  80. ncbi Mixed lineage kinase LZK and antioxidant protein-1 activate NF-kappaB synergistically
    Megumi Masaki
    Department of Biological Chemistry and CREST Core Research for Educational Science and Technology Project, Japan Science and Technology Corporation, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan
    Eur J Biochem 270:76-83. 2003
    ..We also provided evidence that LZK was associated directly with the IKK complex through the kinase domain, and that AOP-1 was recruited to the IKK complex through the binding to LZK...
  81. pmc Antitumour activity of a potent MEK inhibitor RDEA119/BAY 869766 combined with rapamycin in human orthotopic primary pancreatic cancer xenografts
    Qing Chang
    Division of Applied Molecular Oncology, Ontario Cancer Institute Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada
    BMC Cancer 10:515. 2010
    ..The effects of RDEA119/BAY 869766 as a single agent and in combination with rapamycin were studied in 3 early passage primary pancreatic cancer xenografts, OCIP19, 21, and 23, grown orthotopically...
  82. pmc RNA-binding protein AUF1 regulates lipopolysaccharide-induced IL10 expression by activating IkappaB kinase complex in monocytes
    Srijata Sarkar
    Department of Molecular Genetics, Microbiology and Immunology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ 08854 5635, USA
    Mol Cell Biol 31:602-15. 2011
    ..Thus, p40(AUF1) regulates a critical node within the NF-κB signaling pathway to permit IL10 induction for the anti-inflammatory arm of an innate immune response...
  83. ncbi TAK1 is required for TGF-beta 1-mediated regulation of matrix metalloproteinase-9 and metastasis
    A Safina
    Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
    Oncogene 27:1198-207. 2008
    ..Together, these findings suggest that TAK1 contributes to TGF-beta1-mediated tumor angiogenesis and metastasis via a mechanism involving the TAK1-NF-kappaB-MMP-9 pathway...
  84. ncbi Mixed lineage kinase 3 connects reactive oxygen species to c-Jun NH2-terminal kinase-induced mitochondrial apoptosis in genipin-treated PC3 human prostate cancer cells
    Hye Young Hong
    Division of Life Sciences, Kangwon National University, Chuncheon 200 701, Republic of Korea
    Biochem Biophys Res Commun 362:307-12. 2007
    ..Taken together, our observations suggest genipin signaling to apoptosis of PC3 cells is mediated via activation of ROS-dependent MLK3, which leads to downstream activation of JNK...
  85. pmc Membrane recruitment of the kinase cascade scaffold protein Ste5 by the Gbetagamma complex underlies activation of the yeast pheromone response pathway
    P M Pryciak
    Department of Molecular Genetics and Microbiology, University of Massachusetts Medical Center, Worcester Foundation Campus, Shrewsbury, Massachusetts 01545, USA
    Genes Dev 12:2684-97. 1998
    ..Moreover, our results suggest that this event promotes kinase cascade activation by delivering the Ste5-associated kinases to the cell surface kinase Ste20, whose function may depend on Cdc42 and Cdc24...
  86. pmc Mouse models of hepatocarcinogenesis: what can we learn for the prevention of human hepatocellular carcinoma?
    Mihael Vucur
    Department of Internal Medicine III, University Hospital of RWTH Aachen, D 52074 Aachen, Germany
    Oncotarget 1:373-8. 2010
    ..Molecular findings in this mouse model and their possible significance for chemopreventive strategies against HCC are compared to other murine HCC models...
  87. pmc Further insights into the mechanism of hypoxia-induced NFκB. [corrected]
    Andrew Melvin
    College of Life Sciences, Wellcome Trust Centre for Gene Regulation and Expression, University of Dundee, Dundee, Scotland, UK
    Cell Cycle 10:879-82. 2011
    ..Hypoxia prevents IκBα de-sumoylation of Sumo-2/3 chains on critical lysine residues, normally required for K-48 linked polyubiquitination. Our results define a novel pathway regulating NFκB activation...
  88. pmc TAB2 scaffolds TAK1 and NLK in repressing canonical Wnt signaling
    Meng Li
    State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
    J Biol Chem 285:13397-404. 2010
    ..TAB2.NLK complex, suggesting that this TAK1-TAB2-NLK pathway may constitute a negative feedback mechanism for canonical Wnt signaling...
  89. pmc Helicobacter pylori CagA activates NF-kappaB by targeting TAK1 for TRAF6-mediated Lys 63 ubiquitination
    Acacia Lamb
    Department of Biochemistry, College of Medicine, University of Illinois at Urbana Champaign, Urbana, Illinois 61801, USA
    EMBO Rep 10:1242-9. 2009
    ..These findings show that polyubiquitination of TAK1 regulates the activation of NF-kappaB, which in turn is used by H. pylori CagA for the H. pylori-induced inflammatory response...
  90. ncbi Tomato MAPKKKε is a positive regulator of cell-death signaling networks associated with plant immunity
    Shiri Melech-Bonfil
    Department of Molecular Biology and Ecology of Plants, Tel Aviv University, 69978 Tel Aviv, Israel
    Plant J 64:379-91. 2010
    ..Despite the large number of MAP kinase kinase kinases (MAPKKK) encoded in the plant genome, only very few of them have an assigned function...
  91. pmc Axon degeneration: molecular mechanisms of a self-destruction pathway
    Jack T Wang
    Department of Neurobiology, Stanford University School of Medicine, Stanford, CA 94305, USA
    J Cell Biol 196:7-18. 2012
    ..A proposed model of axon degeneration is that nerve insults lead to impaired delivery or expression of a local axonal survival factor, which results in increased intra-axonal calcium levels and calcium-dependent cytoskeletal breakdown...
  92. ncbi The protein kinase genes MAP3K epsilon 1 and MAP3K epsilon 2 are required for pollen viability in Arabidopsis thaliana
    Suraphon Chaiwongsar
    Horticulture Department and Genome Center of Wisconsin, University of Wisconsin, Madison, WI 53706, USA
    Plant J 48:193-205. 2006
    ..Taken together, our results suggest that MAP3Kepsilon1 is required for the normal functioning of the plasma membrane in developing Arabidopsis pollen...
  93. pmc The MAP kinase kinase kinase MLK2 co-localizes with activated JNK along microtubules and associates with kinesin superfamily motor KIF3
    K i Nagata
    MRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK
    EMBO J 17:149-58. 1998
    ....
  94. pmc In silico analysis reveals 75 members of mitogen-activated protein kinase kinase kinase gene family in rice
    Kudupudi Prabhakara Rao
    National Institute of Plant Genome Research, Aruna Asaf Ali Marg, New Delhi 110067, India
    DNA Res 17:139-53. 2010
    ..Further expression analysis of the MAPKKKs in MPSS database revealed that their transcripts were differentially regulated in various stress and tissue-specific libraries...
  95. pmc TAK1 is an essential regulator of BMP signalling in cartilage
    Jae Hyuck Shim
    Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA
    EMBO J 28:2028-41. 2009
    ..Our experiments reveal an essential role for TAK1 in the morphogenesis, growth, and maintenance of cartilage...
  96. ncbi TAB1: an activator of the TAK1 MAPKKK in TGF-beta signal transduction
    H Shibuya
    Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan
    Science 272:1179-82. 1996
    ..TAB1 may function as an activator of the TAK1 MAPKKK in TGF-beta signal transduction...
  97. pmc TAB3, a new binding partner of the protein kinase TAK1
    Peter C F Cheung
    MRC Protein Phosphorylation Unit, School of Life Sciences, MSI WTB complex, Dow Street, University of Dundee, Dundee DD1 5EH, Scotland, UK
    Biochem J 378:27-34. 2004
    ..We also show that the agonist-induced activation of TAK1 complexes requires the phosphorylation of the TAK1 catalytic subunit at a serine/threonine residue(s)...
  98. pmc Autophagy promotes synapse development in Drosophila
    Wei Shen
    Laboratory of Genetics, University of Wisconsin Madison, Madison, WI 53706, USA
    J Cell Biol 187:71-9. 2009
    ..Because autophagy is triggered in response to many environmental cues, our findings suggest that it is perfectly positioned to link environmental conditions with synaptic growth and plasticity...
  99. ncbi Activation of Raf/MEK/ERK/cPLA2 signaling pathway is essential for chlamydial acquisition of host glycerophospholipids
    Heng Su
    Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, USA
    J Biol Chem 279:9409-16. 2004
    ..Furthermore, activation of both ERK1/2 and cPLA2 was dependent on chlamydial growth and restricted within chlamydia-infected cells, suggesting an active manipulation of the host ERK-cPLA2 signaling pathway by chlamydiae...
  100. pmc Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1
    M Saitoh
    Department of Biochemistry, The Cancer Institute, Tokyo, Japanese Foundation for Cancer Research, 1 37 1 Kami Ikebukuro, Toshima ku, Tokyo 170, Japan
    EMBO J 17:2596-606. 1998
    ..The evidence that Trx is a negative regulator of ASK1 suggests possible mechanisms for redox regulation of the apoptosis signal transduction pathway as well as the effects of antioxidants against cytokine- and stress-induced apoptosis...
  101. pmc Structure and transforming potential of the human cot oncogene encoding a putative protein kinase
    J Miyoshi
    Department of Oncogene Research, Osaka University, Japan
    Mol Cell Biol 11:4088-96. 1991
    ..This DNA rearrangement appeared to have occurred during transfection of the tumor DNA into hamster SHOK cells and not in the original thyroid tumor...

Research Grants66

  1. Roles for TAK1 in T cell development, function and tumorigenesis
    YISONG WAN; Fiscal Year: 2010
    ..abstract_text> ..
  2. MLK4 regulation of MAPK signaling
    Deborah N Chadee; Fiscal Year: 2012
    ....
  3. STRUCTURE AND FUNCTION OF 14 3 3 PROTEINS
    Haian Fu; Fiscal Year: 2000
    ..These experiments will lead to a better understanding of the role of 14-3- 3 in signal transduction, which will provide critical insights into the biochemical basis of cell growth regulation and oncogenesis. ..
  4. The role of PKK in NFkappa B activation
    Shiv Pillai; Fiscal Year: 2007
    ..PKK represents a novel enzyme that may be critical in pathways that are important in cancer, inflammation, cell survival, and differentiation. ..
  5. MECHANISMS OF TRANSFORMATION OF HEMATOPOIETIC CELLS
    JAMES MC CUBREY; Fiscal Year: 2001
    ..An understanding of how these signal transduction and apoptotic pathways impinge upon one another will further our comprehension of the consequences of abnormal oncogene activation and tumor progression. ..
  6. Ras/Raf & PI3K/Akt Induced Breast Cancer Drug Resistance
    JAMES MC CUBREY; Fiscal Year: 2007
    ..Throughthese studies,moreinformationwillbe availableto treatbreast andothercancerpatientswithcombinationsof drugs,whichinhibitsignaltransductionand anti-apoptoticpathwaysleadingtodrug resistance. ..
  7. MAP KINASE CASCADE SIGNAL TRANSMISSION AND SPECIFICITY
    Lee Bardwell; Fiscal Year: 2008
    ....
  8. Regulation of Mixed Lineage Kinase 3 by the tumor suppressor protein Merlin
    DEBORAH CHADEE; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  9. Inhibiting the Inhibitor: Small Molecule Screening with Small Pox N1L
    Neal Silverman; Fiscal Year: 2008
    ..Finally compounds that inhibit vaccinia virus would theoretically prevent vaccine (vaccinia) side effects. [unreadable] [unreadable] [unreadable] [unreadable]..
  10. Inhibitor Screens for Five MAPK Kinase Kinases Important in Human Disease
    Gary Johnson; Fiscal Year: 2006
    ....
  11. IQGAP1 in microbial pathogenesis
    David Sacks; Fiscal Year: 2006
    ..Elucidation of the mechanisms of pathogen-host interactions could reveal new targets for diagnosis, therapy and vaccines. ..
  12. Molecular Physioloy of Brain Cation-Cl Cotransporters
    Eric Delpire; Fiscal Year: 2006
    ..abstract_text> ..
  13. Hepatocyte Proliferation During Development: Role of p38
    PHILIP GRUPPUSO; Fiscal Year: 2006
    ..We anticipate that these studies will provide novel insights into the regulation of hepatocyte proliferation during normal development and in the mature rat. ..
  14. SYNOVIAL DYSFUNCTION DUE TO P53 ABNORMALITIES IN RA
    Gary Firestein; Fiscal Year: 2006
    ..abstract_text> ..
  15. Calmodulin and estrogen receptor function
    David Sacks; Fiscal Year: 2006
    ..This knowledge could potentially lead to the ultimate goal of this program, namely the development of novel and specifically targeted pharmacologic agents for the treatment of breast carcinoma. ..
  16. Chk1 signaling in the G2 DNA damage checkpoint
    MATTHEW O CONNELL; Fiscal Year: 2007
    ..The study will yield data that will be important in terms of both the basic biology of the cell cycle and stability of the genome and also in the testing of new approaches and new targets for cancer therapy. [unreadable] [unreadable]..
  17. ROLE OF RHO IN FARNESYLTRANSFERASE INHIBITOR RESPONSES
    George Prendergast; Fiscal Year: 2008
    ..Our long-term goal is to understand the basis for FTI cytotoxicity to leverage drug applications in the oncology clinic ..
  18. Induction of immunological paralysis by CpG DNA
    Ae Kyung Yi; Fiscal Year: 2008
    ..abstract_text> ..
  19. Survivin expression and cancer cell drug resistance
    Fengzhi Li; Fiscal Year: 2008
    ..unreadable] [unreadable]..
  20. RECEPTOR INTERACTION WITH GTP REGULATORY PROTEINS
    Gary Johnson; Fiscal Year: 2008
    ..Cumulatively, the studies will define new strategies for the development of pharmacological ligandsto regulate subsets of receptor functions that will have much more selective effects on target cells and tissues. ..
  21. Melanoma NRAS/BRAF Mutations: A Population-Based Study
    Nancy Thomas; Fiscal Year: 2007
    ..This study is also expected to lead to identification of new hemotherapeutic targets and more efficient testing of inhibitors for NRAS and BRAF signaling, which have recently been developed. ..
  22. Signaling Mechanisms of TCDD-induced AHR Activation
    Ying Xia; Fiscal Year: 2007
    ..abstract_text> ..
  23. CALMODULIN IN NEOPLASTIC TRANSFORMATION OF BREAST TISSUE
    David Sacks; Fiscal Year: 2008
    ..The long-term goal of this program is the development of novel and specifically targeted pharmacologic agents for the treatment of carcinoma. ..
  24. Mechanisms of NF-kappaB Activation in T Lymphocytes
    Zhijian Chen; Fiscal Year: 2008
    ..Such knowledge is crucial to understanding and treating various human diseases, including MALT lymphoma and other immune disorders. ..
  25. RhoB Signaling in Cancer Suppression and Cell Suicide
    George Prendergast; Fiscal Year: 2007
    ..Characterization of these signaling pathways offers a unique opportunity to obtain new insights into cancer pathophysiology and therapeutic response. ..
  26. In Vitro High Throughput Screening Assay for MKP-1(RMI)
    JOHN LAZO; Fiscal Year: 2005
    ..No potent or selective small molecule inhibitors of this protein phosphatase are known. This proposal will provide sufficient reagents to permit a high throughput screening of 100,000 compounds. ..
  27. In Vitro High Throughput Screening Assay for MKP-3(RMI)
    JOHN LAZO; Fiscal Year: 2005
    ..Nonetheless, no potent or selective small molecule inhibitors of this protein phosphatase have been identified. This proposal will provide sufficient reagents to permit a high throughput screening of 100,000 compounds ..
  28. Chemical Complementation Assay for MKP-3 (RMI)
    JOHN LAZO; Fiscal Year: 2005
    ..This proposal will provide sufficient reagents, including cells and DMA transfection vectors, to permit the high throughput screening of 100,000 compounds. ..
  29. IQGAP1 in microbial pathogenesis
    David B Sacks; Fiscal Year: 2010
    ..Elucidation of the mechanisms of pathogen-host interactions could reveal new targets for diagnosis, therapy and vaccines. ..
  30. Identification of Green Tea Polyphenol-Targeted Genes
    Stephen Hsu; Fiscal Year: 2004
    ..Data generated from this proposal may reveal novel drug targets for treatment of head and neck cancer. ..
  31. High-throughput human cell system for compound screening
    ELLEN BERG; Fiscal Year: 2004
    ....
  32. MAP KINASE REGULATION OF MICROGLIAL ACTIVATION
    Narayan Bhat; Fiscal Year: 2004
    ..The suppressive effects of the kinase inhibitors on activation-associated microglial functions; i.e., targeting of oligodendrocytes and myelin phagocytosis will be tested using in vitro models. ..
  33. IKKi expression and regulation in rheumatoid arthritis
    Gary Firestein; Fiscal Year: 2005
    ..We propose to test the hypothesis that IKKi is an important signal transduction pathway that regulates inflammation in chronic arthritis and is a novel target for development of anti-rheumatic agents. ..
  34. MOLECULAR MEDIATORS OF DIABETIC RENAL HYPERTROPHY
    John Kyriakis; Fiscal Year: 2002
    ..These studies, they hope, will expand our knowledge of signal transduction in the diabetic kidney and contribute to the development of novel treatments for diabetic nephropathy using signaling components as targets. ..
  35. Genetic and molecular analysis of Yersinia YopJ
    Neal Silverman; Fiscal Year: 2003
    ..By identifying the true targets of YopJ, new therapeutic means to treat the plague can be devised, thus reducing the potential impact of a bioterrorist attack. ..
  36. MECHANISMS OF SIGNAL INDUCED UBIQUITINATION OF IKBA
    Zhijian Chen; Fiscal Year: 2002
    ..abstract_text> ..
  37. REGULATION OF PERIPHERAL INFLAMMATION BY THE CNS
    Gary Firestein; Fiscal Year: 2002
    ..These studies will provide a basis for understanding the central nervous system-immune system connection as well as explore novel therapeutic targets. ..
  38. BIOCHEMICAL REGULATORS OF BLEOMYCIN INDUCED TUMORS
    JOHN LAZO; Fiscal Year: 2001
    ..The Specific Aims are to: 1) develop cells and mice deficient in BH, 2) develop cells and mice that overexpress BH, 3) isolate and characterize potential proteins that interact with BH and, 4) analyze the regulation of BH expression. ..
  39. PDEF and survivin: cancer prognosis, initiation, progression and metastasis
    Fengzhi Li; Fiscal Year: 2010
    ..These studies may provide novel approaches for cancer prognosis and personalized medicine, by considering survivin and PDEF as interconnected biomarkers and targets. ..
  40. Salivary Stem Cell Identification for Tissue Restoration
    Chih ko Yeh; Fiscal Year: 2004
    ..The results of these studies will ultimately lead to revolutionary treatment of salivary gland diseases. ..
  41. HORMONAL REGULATION OF MAP KINASE VIA RAP1 AND B-RAF
    Philip J S Stork; Fiscal Year: 2010
    ..We will determine the biochemical basis for this specificity of Rap1 for B-Raf in Specific Aim 3. In this aim, we will also establish novel mouse models to test the hypothesis that B-Raf has irreplaceable functions in vivo. ..
  42. ROLE OF NF-KB IN TGF-B1 INDUCED APOPTOSIS OF HEPATOCYTES
    Marcello Arsura; Fiscal Year: 2005
    ..Furthermore, these findings will provide important insights into the role of NF- kappaB/Rel factors in the control of apoptosis of normal and transformed hepatocytes of potential clinical relevance. ..
  43. EUKARYOTIC GENE REGULATION AS STUDIED IN YEAST
    Mark Ptashne; Fiscal Year: 2009
    ..In particular we are testing the idea that this protein, a component of the large complex called the Mediator, is rapidly degraded in cells, and that this instability facilitates activation of transcription ..
  44. Modulators of CL-dependent Transport Processes (RMI)
    Eric Delpire; Fiscal Year: 2005
    ....
  45. Regulation of the MAP Kinase Pathway in Senescence
    George Prendergast; Fiscal Year: 2005
    ..Our goal is to understand the mechanisms underlying the failure in MAP Kinase mitogen signal transduction in culture as a model for signaling failures in aging. ..
  46. UNC Center for Nanosensing the Stressome (RMI)
    Gary Johnson; Fiscal Year: 2004
    ..abstract_text> ..
  47. Epidermal specification mutants of Arabidopsis
    Dominique Bergmann; Fiscal Year: 2004
    ..For the improvement of crop plants, knowledge about the epidermis is particularly relevant for the understanding and engineering of plant defenses and for production of plant biomaterials. ..
  48. MAP KINASES IN OLIGODENDROCYTE CELL SIGNALING
    Narayan Bhat; Fiscal Year: 2005
    ..Putative MAPK-responsive elements and relevant binding activities will be determined by deletion and gel shift analyses ..
  49. Typhoon 9410 Variable Mode Imager
    John Kyriakis; Fiscal Year: 2005
    ..abstract_text> ..
  50. TUMOR GROWTH INHIBITION BY INTERFERON B AND RETINOIDS
    DHAN KALVAKOLANU; Fiscal Year: 2001
    ..This proposal is a translational study that provides a basis and the necessary reagents for future phase II trials with IFN/RA or other drug combinations for cancer therapy. ..
  51. Pheromone Signaling in Pneumocystis Carinii
    Charles Thomas; Fiscal Year: 2009
    ..Through these investigations we hope to gain insights into P. carinii biology which may provide new information for novel drug development to treat PCP. ..
  52. Photoconductive stimulation of synapses and HIV neurotoxins
    Harris Gelbard; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  53. Defining Signal Network Plasticity
    Gary Johnson; Fiscal Year: 2008
    ..A rigorous definition of signal network plasticity will accelerate the translation of basic discovery to therapeutic intervention of human disease, a stated goal of the NIH mission. [unreadable] [unreadable] [unreadable]..
  54. Chemical Complementation Assay for MKP-1 (RMI)
    JOHN LAZO; Fiscal Year: 2005
    ..This proposal will provide sufficient reagents, including cells and DMA transfection vectors, to permit the high throughput screening of 100,000 compounds. ..
  55. RAS/BRAF Melanoma Mutations: Precursors, Risk, Prognosis
    Nancy Thomas; Fiscal Year: 2004
    ..This study is also expected to lead to identification of new chemotherapeutic targets and more efficient testing of inhibitors for NRAS and BRAF signaling, which have recently been developed. ..
  56. The small G protein Rap 1 in T cell activation/anergy
    PHILIP STORK; Fiscal Year: 2005
    ..In addition, we will test the hypothesis that CD28 co-stimulation achieves increased ERK activation, IL-2 production and proliferation by blocking Rap1 activation. ..
  57. Regulatory function of fyn in oral SCC invasion
    Daniel M Ramos; Fiscal Year: 2010
    ..abstract_text> ..
  58. 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]..
  59. Genetic Dissection of Sickle Cell Anemia Phenotypes
    Paola Sebastiani; Fiscal Year: 2006
    ..abstract_text> ..
  60. ORAL MELANOMA: ALPHA V BETA 3 EXPRESSION AND METASTASIS
    Daniel Ramos; Fiscal Year: 2004
    ..Understanding the role beta3 plays in oral melanoma invasion and metastasis may lead to novel prognostic indicators and development of new treatment strategies. ..
  61. Using gene targeting to address the role of LRRK2 in Parkinson's disease
    Bruce Hostager; Fiscal Year: 2007
    ..This knowledge will aid in the identification of the environmental triggers and additional genetic factors that participate in the development of Parkinson's disease. ..
  62. Viral Lysis of Kaposi's Sarcoma Tumor Cells
    Ren Sun; Fiscal Year: 2004
    ....
  63. Viral Genes Essential for MHV-68 Persistent Infection in the Spleen
    Ren Sun; Fiscal Year: 2008
    ..These viruses will strongly stimulate immune responses but will not establish persistent infection to cause diseases, thus a potential vaccine strategy. [unreadable] [unreadable] [unreadable]..
  64. Role of ornithine decarboxylase in Ras transformation
    Lisa Shantz; Fiscal Year: 2006
    ..Keratinocytes from D1/AZ mice will also be used to analyze direct interactions of AZ with cyclin D1, to test whether other properties of AZ are important for deregulation of cell proliferation in tumor development. ..
  65. Role of Interleukin-6 in Gammaherpesvirus replication
    Ren Sun; Fiscal Year: 2007
    ..Our continuous study will be critical to reveal the function of cellular and viral IL-6, a pair of intriguing and important molecules in the life cycle of KSHV. ..
  66. MEKK2/3-MEK5 Interaction/Activation/ERK5 Pathway(RMI)
    BRUCE CUEVAS; Fiscal Year: 2005
    ....