IRAK

Summary

Gene Symbol: IRAK
Description: interleukin 1 receptor associated kinase 1
Alias: IRAK, pelle, interleukin-1 receptor-associated kinase 1, IRAK-1, Pelle homolog
Species: human

Top Publications

  1. ncbi IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines
    Jochen Schmitz
    Schering Plough Biopharma Formerly DNAX Research, Inc, 901 California Avenue, Palo Alto, California 94304, USA
    Immunity 23:479-90. 2005
  2. pmc Differential regulation of interleukin-1 receptor-associated kinase-1 (IRAK-1) and IRAK-2 by microRNA-146a and NF-kappaB in stressed human astroglial cells and in Alzheimer disease
    Jian Guo Cui
    Department of Ophthalmology, Louisiana State University Health Science Center, New Orleans, Louisiana 70112, USA
    J Biol Chem 285:38951-60. 2010
  3. doi A polymorphism in the 3'-UTR of interleukin-1 receptor-associated kinase (IRAK1), a target gene of miR-146a, is associated with rheumatoid arthritis susceptibility
    Anthoula Chatzikyriakidou
    Genetics Unit, Department of Obstetrics and Gynaecology, University of Ioannina, Ioannina, Greece
    Joint Bone Spine 77:411-3. 2010
  4. ncbi The IRAK-1-BCL10-MALT1-TRAF6-TAK1 cascade mediates signaling to NF-kappaB from Toll-like receptor 4
    Wei Dong
    State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China
    J Biol Chem 281:26029-40. 2006
  5. pmc Leishmania-induced IRAK-1 inactivation is mediated by SHP-1 interacting with an evolutionarily conserved KTIM motif
    Issa Abu-Dayyeh
    Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada
    PLoS Negl Trop Dis 2:e305. 2008
  6. ncbi TRAF6 distinctively mediates MyD88- and IRAK-1-induced activation of NF-kappaB
    Masashi Muroi
    National Institute of Health Sciences, 1 18 1 Kamiyoga, Setagaya, Tokyo 158 8501, Japan
    J Leukoc Biol 83:702-7. 2008
  7. ncbi IRAK-2 participates in multiple toll-like receptor signaling pathways to NFkappaB via activation of TRAF6 ubiquitination
    Sinead E Keating
    School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland
    J Biol Chem 282:33435-43. 2007
  8. ncbi IRAK1 serves as a novel regulator essential for lipopolysaccharide-induced interleukin-10 gene expression
    Yingsu Huang
    Department of Medicine, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157, USA
    J Biol Chem 279:51697-703. 2004
  9. ncbi Cutting edge: mouse pellino-2 modulates IL-1 and lipopolysaccharide signaling
    Kang Yeol Yu
    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine and Walther Cancer Institute, 1044 West Walnut Street, Indianapolis, IN 46202, USA
    J Immunol 169:4075-8. 2002
  10. ncbi The interleukin 1 receptor: ligand interactions and signal transduction
    P E Auron
    Department of Pathology, Harvard Medical School, Harvard Institutes of Medicine, Boston, MA 02115, USA
    Cytokine Growth Factor Rev 9:221-37. 1998

Research Grants

  1. FUNCTIONAL ANALYSIS OF THE MOUSE-PELLE-LIKE KINASE
    Maureen Harrington; Fiscal Year: 2003
  2. EPITHELIAL CELL CYTOKINE SECRETION BY INTEGRINS
    Dennis McGee; Fiscal Year: 2005
  3. TLR-mediated Signaling Complex Formation and Regulation of Effector Functions
    Hans Haecker; Fiscal Year: 2012
  4. Yong Jun Liu; Fiscal Year: 2014
  5. Walter J Lukiw; Fiscal Year: 2016
  6. Kun Ping Lu; Fiscal Year: 2015
  7. The novel role and regulation of IRAK in innate immunity
    Liwu Li; Fiscal Year: 2010
  8. FOXP3-microRNA146-NFkB Axis in Tumor Suppression
    Lizhong Wang; Fiscal Year: 2013
  9. Structural biology of Toll like receptor/IL 1R signaling
    Liang Tong; Fiscal Year: 2005
  10. Role of Pellino1 in liver inflammation
    Liselotte E Jensen; Fiscal Year: 2010

Detail Information

Publications278 found, 100 shown here

  1. ncbi IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines
    Jochen Schmitz
    Schering Plough Biopharma Formerly DNAX Research, Inc, 901 California Avenue, Palo Alto, California 94304, USA
    Immunity 23:479-90. 2005
    ..In vivo, IL-33 induces the expression of IL-4, IL-5, and IL-13 and leads to severe pathological changes in mucosal organs...
  2. pmc Differential regulation of interleukin-1 receptor-associated kinase-1 (IRAK-1) and IRAK-2 by microRNA-146a and NF-kappaB in stressed human astroglial cells and in Alzheimer disease
    Jian Guo Cui
    Department of Ophthalmology, Louisiana State University Health Science Center, New Orleans, Louisiana 70112, USA
    J Biol Chem 285:38951-60. 2010
    ..of an NF-κB-regulated miRNA-146a down-regulates expression of the interleukin-1 receptor-associated kinase-1 (IRAK-1), an essential component of Toll-like/IL-1 receptor signaling...
  3. doi A polymorphism in the 3'-UTR of interleukin-1 receptor-associated kinase (IRAK1), a target gene of miR-146a, is associated with rheumatoid arthritis susceptibility
    Anthoula Chatzikyriakidou
    Genetics Unit, Department of Obstetrics and Gynaecology, University of Ioannina, Ioannina, Greece
    Joint Bone Spine 77:411-3. 2010
    ....
  4. ncbi The IRAK-1-BCL10-MALT1-TRAF6-TAK1 cascade mediates signaling to NF-kappaB from Toll-like receptor 4
    Wei Dong
    State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China
    J Biol Chem 281:26029-40. 2006
    ..In this study, we show that IRAK-1 acts as the essential upstream adaptor that recruits BCL10 to the TLR4 signaling complex and mediates signaling ..
  5. pmc Leishmania-induced IRAK-1 inactivation is mediated by SHP-1 interacting with an evolutionarily conserved KTIM motif
    Issa Abu-Dayyeh
    Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada
    PLoS Negl Trop Dis 2:e305. 2008
    ..involved in Toll-like receptor (TLR) signalling and innate immunity such as IL-1 receptor-associated kinase 1 (IRAK-1)...
  6. ncbi TRAF6 distinctively mediates MyD88- and IRAK-1-induced activation of NF-kappaB
    Masashi Muroi
    National Institute of Health Sciences, 1 18 1 Kamiyoga, Setagaya, Tokyo 158 8501, Japan
    J Leukoc Biol 83:702-7. 2008
    MyD88 and IL-1R-associated kinase 1 (IRAK-1) play crucial roles as adaptor molecules in signal transduction of the TLR/IL-1R superfamily, and it is known that expression of these proteins leads to the activation of NF-kappaB in a TNFR-..
  7. ncbi IRAK-2 participates in multiple toll-like receptor signaling pathways to NFkappaB via activation of TRAF6 ubiquitination
    Sinead E Keating
    School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland
    J Biol Chem 282:33435-43. 2007
    ..signaling is known to involve interleukin-1 receptor-associated kinases (IRAKs), however the particular role of IRAK-2 has remained unclear...
  8. ncbi IRAK1 serves as a novel regulator essential for lipopolysaccharide-induced interleukin-10 gene expression
    Yingsu Huang
    Department of Medicine, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157, USA
    J Biol Chem 279:51697-703. 2004
    ....
  9. ncbi Cutting edge: mouse pellino-2 modulates IL-1 and lipopolysaccharide signaling
    Kang Yeol Yu
    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine and Walther Cancer Institute, 1044 West Walnut Street, Indianapolis, IN 46202, USA
    J Immunol 169:4075-8. 2002
    ..protein originally isolated in a two-hybrid screen for proteins interacting with the serine/threonine kinase, pelle. Although mammalian homologs have been identified in mouse and man, the function of pellino is as yet unknown...
  10. ncbi The interleukin 1 receptor: ligand interactions and signal transduction
    P E Auron
    Department of Pathology, Harvard Medical School, Harvard Institutes of Medicine, Boston, MA 02115, USA
    Cytokine Growth Factor Rev 9:221-37. 1998
    ..The recent characterization of an IL-1 receptor associated kinase (IRAK) and a continuous molecular path between this kinase and that which directly phosphorylates IkappaB would seem to ..
  11. pmc Overexpression of an enzymically inactive interleukin-1-receptor-associated kinase activates nuclear factor-kappaB
    B Maschera
    Glaxo Wellcome, Cell Biology Unit, Gunnels Wood Road, Stevenage SG1 2NY, UK
    Biochem J 339:227-31. 1999
    Upon interleukin 1 (IL-1) stimulation, the IL-1-receptor (IL-1R)-associated kinase (IRAK) is rapidly recruited to the IL-1R complex and undergoes phosphorylation...
  12. pmc The atypical PKC-interacting protein p62 channels NF-kappaB activation by the IL-1-TRAF6 pathway
    L Sanz
    Laboratorio Glaxo Wellcome CSIC de Biología Molecular y Celular, Centro de Biología Molecular Severo Ochoa Consejo Superior de Investigaciones Científicas Universidad Autónoma de Madrid, Universidad Autonoma, Canto Blanco, 28049 Madrid, Spain
    EMBO J 19:1576-86. 2000
    ..Together, these results indicate that p62 is an important intermediary not only in TNFalpha but also in IL-1 signaling to NF-kappaB through the specific adapters RIP and TRAF6...
  13. 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
    ..Transient transfection of cells with constitutively active forms of the known IL-1 signaling components MyD88, IRAK, and TRAF-6, or the upstream kinases MKK6 and MKK3, activated p38 MAPK...
  14. ncbi Divergence of bacterial lipopolysaccharide pro-apoptotic signaling downstream of IRAK-1
    Douglas D Bannerman
    Department of Surgery, University of Washington School of Medicine, Seattle, Washington 98104, USA
    J Biol Chem 277:8048-53. 2002
    ..dominant negative constructs, we have identified a role for MyD88 and interleukin-1 receptor-associated kinase-1 (IRAK-1) in mediating LPS pro-apoptotic signaling in human endothelial cells...
  15. ncbi Inhibition of interleukin-1beta -induced NF-kappa B activation by calcium/calmodulin-dependent protein kinase kinase occurs through Akt activation associated with interleukin-1 receptor-associated kinase phosphorylation and uncoupling of MyD88
    Bing Chang Chen
    Department of Pharmacology, College of Medicine, National Taiwan University, Taipei 100, Taiwan
    J Biol Chem 277:24169-79. 2002
    ....
  16. ncbi Pellino 1 is required for interleukin-1 (IL-1)-mediated signaling through its interaction with the IL-1 receptor-associated kinase 4 (IRAK4)-IRAK-tumor necrosis factor receptor-associated factor 6 (TRAF6) complex
    Zhengfan Jiang
    Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    J Biol Chem 278:10952-6. 2003
    ..Toll initiates its signal through the adapter molecule Tube and the serine-threonine kinase Pelle. Pelle is highly homologous to members of the IL-1R-associated kinase (IRAK) family in mammals...
  17. ncbi TIRP, a novel Toll/interleukin-1 receptor (TIR) domain-containing adapter protein involved in TIR signaling
    Liang Hua Bin
    Department of Immunology, National Jewish Medical and Research Center, University of Colorado Health Sciences Center, Denver 80206, USA
    J Biol Chem 278:24526-32. 2003
    ..TIRP also interacts with kinase-inactive mutants of IRAK and IRAK-4, IRAK-2, IRAK-M, and TRAF6...
  18. ncbi Modulation of macrophage responsiveness to lipopolysaccharide by IRAK-1 manipulation
    Joseph Cuschieri
    Department of Surgery, University of Cincinnati, Cincinnati, Ohio 45267, USA
    Shock 21:182-8. 2004
    ..mechanisms involved in these potentially dissimilar events are incomplete, it appears that the proximal kinase IRAK-1 plays a role...
  19. pmc A novel splice variant of interleukin-1 receptor (IL-1R)-associated kinase 1 plays a negative regulatory role in Toll/IL-1R-induced inflammatory signaling
    Navin Rao
    Johnson and Johnson Pharmaceutical Research and Development, 3210 Merryfield Row, San Diego, CA 92121, USA
    Mol Cell Biol 25:6521-32. 2005
    The interleukin-1 (IL-1) receptor-associated kinase 1 (IRAK1) is a member of the IRAK kinase family that plays a pivotal role in the Toll/IL-1 receptor (TIR) family signaling cascade...
  20. pmc The CATERPILLER protein monarch-1 is an antagonist of toll-like receptor-, tumor necrosis factor alpha-, and Mycobacterium tuberculosis-induced pro-inflammatory signals
    Kristi L Williams
    Lineberger Comprehensive Cancer Center, Division of Infectious Diseases, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    J Biol Chem 280:39914-24. 2005
    ..Monarch-1 reduces NFkappaB activation by TLR-signaling molecules MyD88, IRAK-1 (type I interleukin-1 receptor-associated protein kinase), and TRAF6 (TNF receptor (TNFR)-associated factor) as ..
  21. pmc IL-1 receptor-associated kinase 1 is critical for latent membrane protein 1-induced p65/RelA serine 536 phosphorylation and NF-kappaB activation
    Yoon Jae Song
    Department of Medicine, Harvard Medical School, Channing Laboratory, Brigham and Women s Hospital, 181 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 103:2689-94. 2006
    ..Thus, the critical IRAK1 role in LMP1-induced NF-kappaB activation is in mediating p65/RelA S536 phosphorylation through an effect on p38 or other p65 S536 kinases...
  22. pmc Variant IRAK-1 haplotype is associated with increased nuclear factor-kappaB activation and worse outcomes in sepsis
    John Arcaroli
    Intensive Care Unit, Albert Einstein Hospital and Division of Applied Physiology, Heart Institute, University of Sao Paulo, Brazil
    Am J Respir Crit Care Med 173:1335-41. 2006
    The IL-1 receptor-associated kinase (IRAK-1) plays a central role in TLR2- and TLR4-induced activation of nuclear factor (NF)-kappaB, a critical event in the transcriptional regulation of many sepsis-associated proinflammatory mediators...
  23. ncbi Differential regulation of interleukin-1 receptor associated kinase 1 (IRAK1) splice variants
    Jianmin Su
    Department of Biology, Laboratory of Innate Immunity and Inflammation, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA
    Mol Immunol 44:900-5. 2007
    b>IRAK family proteins play critical roles in regulating innate immunity. There are three differentially spliced variants of IRAK1, namely 1, 1b, and 1c...
  24. ncbi MyD88, IRAK1 and TRAF6 knockdown in human chondrocytes inhibits interleukin-1-induced matrix metalloproteinase-13 gene expression and promoter activity by impairing MAP kinase activation
    Rasheed Ahmad
    Department of Medicine, University of Montreal and Research Centre of CHUM Notre Dame Hospital, Montreal, Quebec, Canada H2L 4M1
    Cell Signal 19:2549-57. 2007
    ..These proteins could constitute important therapeutic targets for arthritis-associated cartilage loss by MMP-13...
  25. doi Interleukin-1 receptor-associated kinase (IRAK) -1-mediated NF-kappaB activation requires cytosolic and nuclear activity
    Gang Liu
    Department of Medicine, University of Alabama at Birmingham School of Medicine, Birmingham, AL 35294, USA
    FASEB J 22:2285-96. 2008
    Interleukin-1 receptor-associated kinase (IRAK) -1 plays an essential role in Toll-like receptor/interleukin-1 receptor (TLR/IL-1R) -associated NF-kappaB activation through its involvement in IKK activation, which then leads to subsequent ..
  26. pmc Tolerance induced via TLR2 and TLR4 in human dendritic cells: role of IRAK-1
    Valerie Albrecht
    Helmholtz Center München, German Research Center for Environmental Health and Asklepios Fachkliniken Gauting, Inflammatory Lung Diseases, 82131 Gauting, Germany
    BMC Immunol 9:69. 2008
    ..We have analysed tolerance induced in human in-vitro generated DCs by repeated stimulation with ligands for TLR4 and TLR2...
  27. doi The kinase activities of interleukin-1 receptor associated kinase (IRAK)-1 and 4 are redundant in the control of inflammatory cytokine expression in human cells
    Kyung W Song
    Department of Inflammation Discovery, Roche Palo Alto, United States
    Mol Immunol 46:1458-66. 2009
    b>IRAK-1 and IRAK-4 are protein kinases that mediate signaling by Toll/IL1/Plant R (TIR) domain-containing receptors including the IL-1, IL-18, and Toll-like receptors (TLRs)...
  28. ncbi IRAK: a kinase associated with the interleukin-1 receptor
    Z Cao
    Molecular Biology Department, Tularik, Incorporated, South San Francisco, CA 94080, USA
    Science 271:1128-31. 1996
    ..The primary amino acid sequence of IRAK shares similarity with that of Pelle, a protein kinase that is essential for the activation of a NF-kappa B homolog in Drosophila.
  29. ncbi TRAF6 is a signal transducer for interleukin-1
    Z Cao
    Tularik Inc, South San Francisco, California 94080, USA
    Nature 383:443-6. 1996
    ..IL-1 treatment of 293 cells induces the association of TRAF6 with IRAK, a serine/threonine kinase that is rapidly recruited to the IL-1 receptor after IL-1 induction...
  30. ncbi A cytokine-responsive IkappaB kinase that activates the transcription factor NF-kappaB
    J A DiDonato
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California at San Diego, La Jolla 92093 0636, USA
    Nature 388:548-54. 1997
    ..A component of IKK was molecularly cloned and identified as a serine kinase. IKK turns out to be the long-sought-after protein kinase that mediates the critical regulatory step in NF-kappaB activation...
  31. ncbi MyD88, an adapter protein involved in interleukin-1 signaling
    K Burns
    Institute of Biochemistry, Lausanne Branch, University of Lausanne, Switzerland
    J Biol Chem 273:12203-9. 1998
    ..MyD88-induced NF-kappaB activation is inhibited by the dominant negative versions of TRAF6 and IRAK, which also inhibit IL-1-induced NF-kappaB activation...
  32. pmc The human toll signaling pathway: divergence of nuclear factor kappaB and JNK/SAPK activation upstream of tumor necrosis factor receptor-associated factor 6 (TRAF6)
    M Muzio
    Department of Immunology and Cell Biology, Mario Negri Institute, I 20157 Milan, Italy
    J Exp Med 187:2097-101. 1998
    ..Conversely, a dominant negative version of TRAF6 failed to block hToll-induced activation of stress-activated protein kinase/c-Jun NH2-terminal kinases, thus suggesting an early divergence of the two pathways...
  33. ncbi IRAK-M is a novel member of the Pelle/interleukin-1 receptor-associated kinase (IRAK) family
    H Wesche
    Tularik Inc, South San Francisco, California 94080, USA
    J Biol Chem 274:19403-10. 1999
    The interleukin-1 receptor-associated kinase (IRAK) was first described as a signal transducer for interleukin-1 (IL-1) and has later been implicated in signal transduction of other members of the Toll/IL-1 receptor family...
  34. ncbi Impaired cytokine signaling in mice lacking the IL-1 receptor-associated kinase
    J A Thomas
    Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235, USA
    J Immunol 163:978-84. 1999
    ..type 1 IL-1R (IL-1R1) and the IL-18R by their cognate ligands induces recruitment of the IL-1R-associated kinase (IRAK)...
  35. ncbi Tollip, a new component of the IL-1RI pathway, links IRAK to the IL-1 receptor
    K Burns
    Institute of Biochemistry, University of Lausanne, BIL Biomedical Research Centre, Chemin des Boveresses 155, CH 1066 Epalinges, Switzerland
    Nat Cell Biol 2:346-51. 2000
    ..two different receptor chains (IL-1Rs), IL-1RI and IL-1RAcP, the adaptor protein MyD88, the serine/threonine kinase IRAK and a new protein, which we have named Tollip...
  36. pmc Interleukin-1 (IL-1) receptor-associated kinase leads to activation of TAK1 by inducing TAB2 translocation in the IL-1 signaling pathway
    G Takaesu
    Department of Molecular Biology, Graduate School of Science, Nagoya University, Nagoya 464 8602, Japan
    Mol Cell Biol 21:2475-84. 2001
    ..The serine/threonine kinase IL-1 receptor-associated kinase (IRAK) also plays a role in IL-1 signaling, being recruited to the IL-1 receptor complex early in the signal cascade...
  37. pmc IL-1-induced NFkappa B and c-Jun N-terminal kinase (JNK) activation diverge at IL-1 receptor-associated kinase (IRAK)
    X Li
    Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    Proc Natl Acad Sci U S A 98:4461-5. 2001
    Mutant I1A cells, lacking IL-1 receptor-associated kinase (IRAK) mRNA and protein, have been used to study the involvement of IRAK in NFkappaB and c-Jun N-terminal kinase (JNK) activation...
  38. ncbi IRAK-mediated translocation of TRAF6 and TAB2 in the interleukin-1-induced activation of NFkappa B
    Y Qian
    Department of Immunology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    J Biol Chem 276:41661-7. 2001
    The interleukin-1 (IL-1) receptor-associated kinase (IRAK) is required for the IL-1-induced activation of nuclear factor kappaB and c-Jun N-terminal kinase...
  39. ncbi Gram-negative flagellin-induced self-tolerance is associated with a block in interleukin-1 receptor-associated kinase release from toll-like receptor 5
    Steven B Mizel
    Department of Microbiology and Immunology, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157, USA
    J Biol Chem 277:22414-20. 2002
    ..of a decrease in the steady-state level of toll-like receptor 5 (TLR5) or interleukin-1 receptor associated kinase (IRAK), but it is associated with a block in the release of IRAK from the TLR5 complex in flagellin-tolerant cells...
  40. pmc Interleukin-1 (IL-1) receptor-associated kinase-dependent IL-1-induced signaling complexes phosphorylate TAK1 and TAB2 at the plasma membrane and activate TAK1 in the cytosol
    Zhengfan Jiang
    Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    Mol Cell Biol 22:7158-67. 2002
    Interleukin-1 (IL-1) receptor-associated kinase (IRAK) plays an important role in the sequential formation and activation of IL-1-induced signaling complexes...
  41. pmc Inhibition of interleukin 1 receptor/Toll-like receptor signaling through the alternatively spliced, short form of MyD88 is due to its failure to recruit IRAK-4
    Kimberly Burns
    Institute of Biochemistry, University of Lausanne, BIL Biomedical Research Center, CH 1066 Epalinges, Switzerland
    J Exp Med 197:263-8. 2003
    ..allows it to link the TIR domain of IL-1R/TLR with the DD of the Ser/Thr kinase termed IL-1R-associated kinase (IRAK)-1...
  42. ncbi Bruton's tyrosine kinase is a Toll/interleukin-1 receptor domain-binding protein that participates in nuclear factor kappaB activation by Toll-like receptor 4
    Caroline A Jefferies
    Cytokine Research Group, Department of Biochemistry and Biotechnology Institute, Trinity College, Dublin 2, Ireland
    J Biol Chem 278:26258-64. 2003
    ..Our findings implicate Btk as a Toll/interleukin-1 receptor domain-binding protein that is important for NFkappaB activation by TLR4...
  43. ncbi Sequential autophosphorylation steps in the interleukin-1 receptor-associated kinase-1 regulate its availability as an adapter in interleukin-1 signaling
    Christian Kollewe
    Department of Pharmacology, Hannover Medical School, D 30623 Hannover, Germany
    J Biol Chem 279:5227-36. 2004
    The interleukin-1 receptor-associated kinase 1 (IRAK-1) is an important adapter in the signaling complex of the Toll/interleukin-1 (IL-1) receptor family...
  44. pmc Interleukin-1 receptor-associated kinase-1 plays an essential role for Toll-like receptor (TLR)7- and TLR9-mediated interferon-{alpha} induction
    Satoshi Uematsu
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Suita Osaka 565 0871, Japan
    J Exp Med 201:915-23. 2005
    ..Here we show an essential role of IL-1 receptor-associated kinase (IRAK)-1 in TLR7- and TLR9-mediated IRF7 signaling pathway. IRAK-1 directly bound and phosphorylated IRF7 in vitro...
  45. ncbi Intracellular trafficking of interleukin-1 receptor I requires Tollip
    Brian Brissoni
    Department of Biochemistry, University of Lausanne, BIL Biomedical Research Center, Chemin des Boveresses 155, CH 1066 Epalinges, Switzerland
    Curr Biol 16:2265-70. 2006
    ..Our findings suggest that Tollip functions as an endosomal adaptor linking IL-1RI, via Tom1, to the endosomal degradation machinery...
  46. pmc Hepatitis C virus nonstructural protein 5A modulates the toll-like receptor-MyD88-dependent signaling pathway in macrophage cell lines
    Takayuki Abe
    Department of Molecular Virology, Graduate School of Medicine, Osaka University, Osaka, Japan
    J Virol 81:8953-66. 2007
    ..These results suggest that the expression of HCV proteins modulates the TLR signaling pathway in immune cells...
  47. ncbi The IRAK-catalysed activation of the E3 ligase function of Pellino isoforms induces the Lys63-linked polyubiquitination of IRAK1
    Alban Ordureau
    MRC Protein Phosphorylation Unit, The Sir James Black Centre, College of Life Sciences, University of Dundee, Dow Street, Dundee DD15 5EH, Scotland, UK
    Biochem J 409:43-52. 2008
    The protein kinases IRAK [IL-1 (interleukin 1) receptor-associated kinase] 1 and 4 play key roles in a signalling pathway by which bacterial infection or IL-1 trigger the production of inflammatory mediators...
  48. pmc Interleukin-1 (IL-1) induces the Lys63-linked polyubiquitination of IL-1 receptor-associated kinase 1 to facilitate NEMO binding and the activation of IkappaBalpha kinase
    Mark Windheim
    MRC Protein Phosphorylation Unit, College of Life Sciences, The Sir James Black Centre, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, United Kingdom
    Mol Cell Biol 28:1783-91. 2008
    ..Our data suggest a model in which the recruitment of the NEMO-IKK complex to K63-pUb-IRAK1 and the recruitment of the TAK1 complex to TRAF6 facilitate the TAK1-catalyzed activation of IKK by the TRAF6-IRAK1 complex...
  49. pmc Identification of IRAK1 as a risk gene with critical role in the pathogenesis of systemic lupus erythematosus
    Chaim O Jacob
    The Lupus Genetic Group, Department of Medicine, University of Southern California, 2011 Zonal Avenue, Los Angeles, CA 90033, USA
    Proc Natl Acad Sci U S A 106:6256-61. 2009
    ..This demonstration of an X chromosome gene as a disease susceptibility factor in human SLE raises the possibility that the gender difference in SLE may in part be attributed to sex chromosome genes...
  50. doi Down syndrome candidate region-1 protein interacts with Tollip and positively modulates interleukin-1 receptor-mediated signaling
    Jae Youn Lee
    Department of Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120 749, Korea
    Biochim Biophys Acta 1790:1673-80. 2009
    ..DSCR1 modulates calcineurin phosphatase activity, though its functional role is incompletely understood...
  51. doi Immune complex-mediated cell activation from systemic lupus erythematosus and rheumatoid arthritis patients elaborate different requirements for IRAK1/4 kinase activity across human cell types
    Eugene Y Chiang
    Department of Immunology, Genentech, Inc, South San Francisco, CA 94080, USA
    J Immunol 186:1279-88. 2011
    ..These data reveal important species differences and elaborate cell type requirements for IRAK1/4 kinase activity...
  52. ncbi IRAK (Pelle) family member IRAK-2 and MyD88 as proximal mediators of IL-1 signaling
    M Muzio
    University of Michigan Medical School, Department of Pathology, Ann Arbor, MI 48109, USA
    Science 278:1612-5. 1997
    ..in mammals and is similar to the Toll pathway in Drosophila: the IL-1R-associated kinase (IRAK) is homologous to Pelle. Two additional proximal mediators were identified that are required for IL-1R-induced NF-kappaB activation: IRAK-..
  53. pmc IRAK-4: a novel member of the IRAK family with the properties of an IRAK-kinase
    Shyun Li
    Tularik, Inc, 2 Corporate Drive, South San Francisco, CA 94080, USA
    Proc Natl Acad Sci U S A 99:5567-72. 2002
    ..The fruit fly Drosophila melanogaster has one member of this family of kinases, termed Pelle. The complexity of this pathway is vastly increased in vertebrates, and several Pelle homologs have been described ..
  54. ncbi Lipopolysaccharide- and lipoteichoic acid-induced tolerance and cross-tolerance: distinct alterations in IL-1 receptor-associated kinase
    Randy Jacinto
    Program in Molecular Medicine and Departments of Internal Medicine Infectious Diseases, Biochemistry, and Microbiology and Immunology, Wake Forest University Medical Center, Winston Salem, NC 27157, USA
    J Immunol 168:6136-41. 2002
    ..We observe that down-regulation of IL-1R-associated kinase (IRAK) protein level and kinase activity closely correlates with the development of cross-tolerance...
  55. ncbi Dysregulation of LPS-induced Toll-like receptor 4-MyD88 complex formation and IL-1 receptor-associated kinase 1 activation in endotoxin-tolerant cells
    Andrei E Medvedev
    Department of Microbiology and Immunology, University of Maryland, Baltimore 21201, USA
    J Immunol 169:5209-16. 2002
    ..Comparable levels of mRNA and protein for myeloid differentiation factor 88 (MyD88), IL-1R-associated kinase 1 (IRAK-1), and TNFR-associated factor-6 were found in normal and LPS-tolerant monocytes, while MD-2 mRNA expression was ..
  56. ncbi Regulation of interleukin receptor-associated kinase (IRAK) phosphorylation and signaling by iota protein kinase C
    Vidya Mamidipudi
    Program in Cell and Molecular Biosciences, Department of Biological Sciences, Auburn University, Auburn, Alabama 36849, USA
    J Biol Chem 279:4161-5. 2004
    We have previously shown that the activity of the interleukin-1 (IL-1) receptor-associated kinase (IRAK) is required for nerve growth factor (NGF)-induced activation of NF-kappaB and cell survival ((2002) J. Biol. Chem. 277, 28010-28018)...
  57. ncbi IRAK4 kinase activity is redundant for interleukin-1 (IL-1) receptor-associated kinase phosphorylation and IL-1 responsiveness
    Jinzhong Qin
    Department of Immunology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    J Biol Chem 279:26748-53. 2004
    Interleukin-1 (IL-1) stimulation leads to the recruitment of interleukin-1 receptor-associated kinase (IRAK) to the IL-1 receptor, where IRAK is phosphorylated, ubiquitinated, and eventually degraded...
  58. ncbi Interactions of sequence variants in interleukin-1 receptor-associated kinase4 and the toll-like receptor 6-1-10 gene cluster increase prostate cancer risk
    Jielin Sun
    Medical Center Boulevard, Winston Salem, NC 27157, USA
    Cancer Epidemiol Biomarkers Prev 15:480-5. 2006
    ..Interleukin-1 receptor-associated kinases (IRAK) 1 and 4 are critical components in the TLR signaling pathway...
  59. pmc Pellino 3b negatively regulates interleukin-1-induced TAK1-dependent NF kappaB activation
    Hui Xiao
    Department of Immunology, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
    J Biol Chem 283:14654-64. 2008
    IL-1 receptor-associated kinase (IRAK) is phosphorylated, ubiquitinated, and degraded upon interleukin-1 (IL-1) stimulation...
  60. pmc Lys63-linked polyubiquitination of IRAK-1 is required for interleukin-1 receptor- and toll-like receptor-mediated NF-kappaB activation
    Dietrich B Conze
    Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Mol Cell Biol 28:3538-47. 2008
    ..through the interleukin-1 receptor (IL-1R) and some Toll-like receptors (TLRs) induces ubiquitination of TRAF6 and IRAK-1, signaling components required for NF-kappaB and mitogen-activated protein kinase activation...
  61. ncbi Regulation of IL-1 receptor-associated kinases by lipopolysaccharide
    Jean Hu
    Section of Infectious Diseases, Department of Medicine, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA
    J Immunol 168:3910-4. 2002
    IL-1R-associated kinase (IRAK) plays a pivotal role in IL-1R/Toll-like receptor (TLR)-mediated signaling and NF-kappaB activation...
  62. ncbi Signaling events induced by lipopolysaccharide-activated toll-like receptor 2
    R B Yang
    Department of Molecular Biology, Genentech, Inc, San Francisco, CA 94080, USA
    J Immunol 163:639-43. 1999
    ..Concomitant with receptor oligomerization, the IL-1R-associated kinase (IRAK) is recruited to the TLR2 complex...
  63. pmc Recruitment of IRAK to the interleukin 1 receptor complex requires interleukin 1 receptor accessory protein
    J Huang
    Tularik, Inc, South San Francisco, CA 94080, USA
    Proc Natl Acad Sci U S A 94:12829-32. 1997
    ..An early IL-1 signaling event is the recruitment of the Ser/Thr kinase IRAK to the type I IL-1 receptor (IL-1RI)...
  64. pmc T6BP, a TRAF6-interacting protein involved in IL-1 signaling
    L Ling
    Tularik Inc, South San Francisco, CA 94080, USA
    Proc Natl Acad Sci U S A 97:9567-72. 2000
    ..Formation of the TRAF6-T6BP complex depends on the presence of the IL-1 receptor-associated kinase (IRAK)...
  65. ncbi IRAK1b, a novel alternative splice variant of interleukin-1 receptor-associated kinase (IRAK), mediates interleukin-1 signaling and has prolonged stability
    L E Jensen
    Department of Pharmacology and Center for Pharmacogenetics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 276:29037-44. 2001
    ..The presence of an alternative splice variant of IRAK1, which is functionally active and highly stable following IL-1 stimulation, adds further complexity to the control mechanisms that govern IL-1 signaling...
  66. ncbi Identification of interleukin 1 receptor-associated kinase as a conserved component in the p75-neurotrophin receptor activation of nuclear factor-kappa B
    Vidya Mamidipudi
    Department of Biological Sciences, Program in Cell and Molecular Biosciences, Auburn University, Auburn, Alabama 36849, USA
    J Biol Chem 277:28010-8. 2002
    ..co-immunoprecipitation, we demonstrate an NGF-dependent association of interleukin 1 receptor-associated kinase (IRAK) with the p75 neurotrophin receptor in PC12 cells...
  67. ncbi Identification of TIFA as an adapter protein that links tumor necrosis factor receptor-associated factor 6 (TRAF6) to interleukin-1 (IL-1) receptor-associated kinase-1 (IRAK-1) in IL-1 receptor signaling
    Hiroshi Takatsuna
    Division of Cellular and Molecular Biology, Department of Cancer Biology, The Institute of Medical Science, The University of Tokyo, Shirokanedai, Minato ku, Tokyo 108 8639, Japan
    J Biol Chem 278:12144-50. 2003
    ..members of the Toll/interleukin-1 (IL-1) receptor family by interacting with IL-1 receptor-associated kinase-1 (IRAK-1) after IRAK-1 is released from the receptor-MyD88 complex upon IL-1 stimulation...
  68. ncbi SIGIRR, a negative regulator of Toll-like receptor-interleukin 1 receptor signaling
    David Wald
    Cleveland Clinic Foundation, Department of Immunology, Cleveland, Ohio 44195, USA
    Nat Immunol 4:920-7. 2003
    ..Finally, biochemical analysis indicated that SIGIRR binds to the TLR-IL-1R signaling components in a ligand-dependent way. Our data show that SIGIRR functions as a biologically important modulator of TLR-IL-1R signaling...
  69. ncbi [Role of transduce molecules and modulatory factors of signal pathways of Toll-like receptor in inflammatory response of children with sepsis]
    Wei Guo Yang
    Pediatric Intensive Care Unit, Shenzhen Children Hospital, Shenzhen 518026, Guangdong, China
    Zhongguo Wei Zhong Bing Ji Jiu Yi Xue 20:561-4. 2008
    ..To investigate the role of transduce molecules and modulatory factors of signal pathways of Toll-like receptors (TLRs) in aberrant inflammatory response in children with sepsis...
  70. pmc Upregulated miR-146a expression in peripheral blood mononuclear cells from rheumatoid arthritis patients
    Kaleb M Pauley
    Department of Oral Biology, University of Florida, Gainesville, Florida 32610, USA
    Arthritis Res Ther 10:R101. 2008
    ..In this study, the expression of selected microRNAs is examined in rheumatoid arthritis...
  71. doi TNF/IL-1/NIK/NF-kappa B transduction pathway: a comparative study in normal and pathological human prostate (benign hyperplasia and carcinoma)
    C Nunez
    Department of Cell Biology and Genetics, University of Alcala, Madrid, Spain
    Histopathology 53:166-76. 2008
    ..The aim was to investigate upstream and downstream components of NIK transduction pathway in normal (NP), benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN) and prostatic carcinoma (PC)...
  72. doi Staphylococcal pericarditis, and liver and paratracheal abscesses as presentations in two new cases of interleukin-1 receptor associated kinase 4 deficiency
    Jeannette L Comeau
    Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada
    Pediatr Infect Dis J 27:170-4. 2008
    A deficiency in the interleukin-1 receptor activated kinase 4 (IRAK-4) has recently been associated with severe recurrent, predominantly Gram-positive bacterial infections.
  73. doi Up-regulation of IRAK-M is essential for endotoxin tolerance induced by a low dose of lipopolysaccharide in Kupffer cells
    Zuo Jin Liu
    Department of Hepatobiliary Surgery, Second Affiliated Hospital, Chongqing University of Medical Sciences, Chongqing, China
    J Surg Res 150:34-9. 2008
    ..The latter proteins may be counter regulatory, including interleukin-1 receptor-associated kinase M (IRAK-M) expression...
  74. pmc Epstein-Barr virus latent membrane protein 1 activation of NF-kappaB through IRAK1 and TRAF6
    Micah Luftig
    Program in Virology, Department of Microbiology and Molecular Genetics, Harvard Medical School, Channing Laboratory Brigham and Women s Hospital, 181 Longwood Avenue, Boston, MA 02115
    Proc Natl Acad Sci U S A 100:15595-600. 2003
    ..lacking expression of TRAF2, TRAF5, TRAF6, IKKalpha, IKKbeta, IKKgamma, TAB2, IL-1 receptor-associated kinase (IRAK)1, or IRAK4 to assess their roles in LMP1-mediated NF-kappaB activation...
  75. pmc Toll-like receptor 3-mediated activation of NF-kappaB and IRF3 diverges at Toll-IL-1 receptor domain-containing adapter inducing IFN-beta
    Zhengfan Jiang
    University of Toronto, Toronto, ON, Canada M5G 2M9
    Proc Natl Acad Sci U S A 101:3533-8. 2004
    ..double-stranded RNA-triggered, Toll-like receptor 3 (TLR3)-mediated signaling is independent of MyD88, IRAK4, and IRAK. Instead, TRAF6, TAK1, and TAB2 are recruited to TLR3 on poly(I.C) stimulation...
  76. pmc Expression of interleukin-1 receptor-associated kinase-1 in non-small cell lung carcinoma and preneoplastic lesions
    Carmen Behrens
    Departmentsof Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030 4009, USA
    Clin Cancer Res 16:34-44. 2010
    To identify the pattern of interleukin-1 receptor-associated kinase (IRAK-1) protein expression in non-small cell lung carcinoma (NSCLC) and corresponding preneoplastic lesions.
  77. pmc Clinical features and outcome of patients with IRAK-4 and MyD88 deficiency
    Capucine Picard
    Study Center of Primary Immunodeficiencies, Assistance Publique Hopitaux de Paris, Paris, France
    Medicine (Baltimore) 89:403-25. 2010
    Autosomal recessive interleukin-1 receptor-associated kinase (IRAK)-4 and myeloid differentiation factor (MyD)88 deficiencies impair Toll-like receptor (TLR)- and interleukin-1 receptor-mediated immunity...
  78. pmc Structure-function similarities between a plant receptor-like kinase and the human interleukin-1 receptor-associated kinase-4
    Dörte Klaus-Heisen
    Laboratory of Plant Microbe Interactions, INRA CNRS, BP 52627, 31326 Castanet Tolosan Cedex, France
    J Biol Chem 286:11202-10. 2011
    ..to the kinase domain and share an evolutionary origin with the animal interleukin-1 receptor-associated kinase/Pelle-soluble kinases...
  79. ncbi Shigella sonnei meningitis due to interleukin-1 receptor-associated kinase-4 deficiency: first association with a primary immune deficiency
    Helen Chapel
    Department of Clinical Immunology, Nuffield Department of Medicine, John Radcliffe Hospital, Headington, Oxford, United Kingdom
    Clin Infect Dis 40:1227-31. 2005
    Inherited interleukin-1-receptor-associated kinase-4 (IRAK-4) deficiency is a recently described immunodeficiency associated with pyogenic bacterial infections and a poor inflammatory response...
  80. pmc IRAK-4 inhibitors for inflammation
    Zhulun Wang
    Amgen Inc, South San Francisco, CA 94080, USA
    Curr Top Med Chem 9:724-37. 2009
    ..Out of four members in the mammalian IRAK family, IRAK-4 is considered to be the "master IRAK", the only family member indispensable for IL-1R/TLR signaling...
  81. pmc Induction of beta defensin 2 by NTHi requires TLR2 mediated MyD88 and IRAK-TRAF6-p38MAPK signaling pathway in human middle ear epithelial cells
    Haa Yung Lee
    The Gonda Department of Cell and Molecular Biology, House Ear Institute, Los Angeles, CA, USA
    BMC Infect Dis 8:87. 2008
    ..We believe that this report is the first attempt to elucidate NTHi induced beta-defensin expression in airway mucosa, which includes the middle ear...
  82. doi Expression of miR-146a/b is associated with the Toll-like receptor 4 signal in coronary artery disease: effect of renin-angiotensin system blockade and statins on miRNA-146a/b and Toll-like receptor 4 levels
    Yuji Takahashi
    Division of Cardiology, Department of Internal Medicine and Memorial Heart Center, Iwate Medical University School of Medicine, Uchimaru 19 1, Morioka 020 8505, Iwate, Japan
    Clin Sci (Lond) 119:395-405. 2010
    ..The present study demonstrates that combined treatment with an ARB and a statin decreases miR-146a/b and the TLR4 signal in CAD patients, possibly contributing to the anti-atherogenic effects of ARBs and statins in this disorder...
  83. doi Dr. Jekyll and Mr. Hyde: a short history of anthrax
    Maxime Schwartz
    Institut Pasteur, 25 rue du Docteur Roux, 75015 Paris, France
    Mol Aspects Med 30:347-55. 2009
    ..letters crisis, following the discovery of a major bacterial warfare program in the USSR and the realization that Irak had been on the verge of using anthrax as a weapon during the first Gulf war, had the consequence of putting ..
  84. ncbi RDP58 is a novel and potentially effective oral therapy for ulcerative colitis
    Simon Travis
    Gastroenterology Unit, John Radcliffe Hospital, Oxford, UK
    Inflamm Bowel Dis 11:713-9. 2005
    ..decapeptide that inhibits synthesis of proinflammatory cytokines by disrupting cell signaling at the pre-MAPK MyD88-IRAK-TRAF6 protein complex...
  85. ncbi Regulation of IRAK-4 kinase activity via autophosphorylation within its activation loop
    Hong Cheng
    Department of Inflammation, Millennium Pharmaceuticals, Inc, Cambridge, MA 02139, USA
    Biochem Biophys Res Commun 352:609-16. 2007
    Interleukin-1 stimulation leads to the recruitment of MyD88, interleukin-1 receptor-associated kinase 1 (IRAK-1) and interleukin-1 receptor-associated kinase 4 (IRAK-4) to the IL-1 receptor...
  86. doi Differential gene expression of interleukin-1 receptor associated kinase-1 and interleukin-1 receptor associated kinase-M in peripheral blood mononuclear cells of young and aged rats following preconditioning with endotoxin
    Yingzhe Li
    Department of Surgery, Duke University, USA
    Shock 31:55-63. 2009
    The IL-1 receptor-associated kinase 1 (IRAK-1) and IRAK-M are key signaling molecules in cellular responses to endotoxin initiated through the Toll-like receptors (TLRs)...
  87. doi The critical role of kinase activity of interleukin-1 receptor-associated kinase 4 in animal models of joint inflammation
    Magdalena Koziczak-Holbro
    Novartis Institutes for BioMedical Research, Basel, Switzerland
    Arthritis Rheum 60:1661-71. 2009
    We have previously reported that the kinase activity of interleukin-1 receptor-associated kinase 4 (IRAK-4) is important for Toll-like receptor and interleukin-1 receptor signaling in vitro...
  88. doi Survival and cardiac remodeling after myocardial infarction are critically dependent on the host innate immune interleukin-1 receptor-associated kinase-4 signaling: a regulator of bone marrow-derived dendritic cells
    Yuichiro Maekawa
    Toronto General Hospital, University Health Network, Toronto, Ontario M5G2C4, Canada
    Circulation 120:1401-14. 2009
    ..Interleukin-1 receptor-associated kinase-4 (IRAK-4), downstream of Toll/interleukin-1 receptor signaling, has an essential role in regulating the innate immune ..
  89. doi Steady-state kinetic characterization of kinase activity and requirements for Mg2+ of interleukin-1 receptor-associated kinase-4
    Mohammad Hekmat-Nejad
    Department of Virology, Roche Palo Alto, LLC, 3431 Hillview Avenue, Palo Alto, California 94304, USA
    Biochemistry 49:1495-506. 2010
    Interleukin-1 receptor-associated kinase-4 (IRAK-4) is a Ser/Thr-specific protein kinase that plays a critical role in intracellular signaling cascades mediated by Toll-like and interleukin-1 (IL-1) receptors...
  90. ncbi The IL1 receptor accessory protein is responsible for the recruitment of the interleukin-1 receptor associated kinase to the IL1/IL1 receptor I complex
    F Volpe
    Glaxo Wellcome, Cell Biology Unit, Stevenage, UK
    FEBS Lett 419:41-4. 1997
    Following interleukin-1 (IL1) stimulation, an IL1 receptor associated kinase (IRAK) is rapidly recruited to the receptor complex...
  91. ncbi Transcriptional regulator CTCF controls human interleukin 1 receptor-associated kinase 2 promoter
    Igor Kuzmin
    Basic Research Program, SAIC Frederick, Inc, Frederick, MD 21702, USA
    J Mol Biol 346:411-22. 2005
    ..In particular, a family of four interleukin 1 receptor-associated kinases (IRAK) regulates responsiveness to bacterial endotoxins...
  92. pmc Identification of critical residues of the MyD88 death domain involved in the recruitment of downstream kinases
    Maria Loiarro
    Department of Public Health and Cell Biology, University of Rome Tor Vergata, 00133 Rome, Italy
    J Biol Chem 284:28093-103. 2009
    ..We performed a site-directed mutagenesis of MyD88 residues, conserved in death domains of the homologous FADD and Pelle proteins, and analyzed the effect of the mutations on MyD88 signaling...
  93. ncbi [The influence of over expression of interleukin-1 receptor-associated kinase 1 on bacterial lipoprotein-induced tolerance]
    Chong Hui Li
    Hepatobiliary Surgery Institute, PLA General Hospital, Beijing 100853, China
    Zhongguo Wei Zhong Bing Ji Jiu Yi Xue 22:8-11. 2010
    To investigate Toll-like receptor 2 (TLR2) and interleukin-1 receptor-associated kinase 1 (IRAK-1) in bacterial lipoprotein (BLP) tolerance.
  94. pmc A novel splice variant of mouse interleukin-1-receptor-associated kinase-1 (IRAK-1) activates nuclear factor-kappaB (NF-kappaB) and c-Jun N-terminal kinase (JNK)
    Ken Yanagisawa
    Department of Biochemistry, Jichi Medical School, 3311 1 Yakushiji, Minamikawachi Machi, Kawachi gun, Tochigi, 329 0498, Japan
    Biochem J 370:159-66. 2003
    Interleukin-1 (IL-1)-receptor-associated kinase (IRAK) is an indispensable signalling molecule for host-defence responses initiated by a variety of ligands that bind to members of the Toll/IL-1 receptor family...
  95. ncbi Poly(I-C)-induced Toll-like receptor 3 (TLR3)-mediated activation of NFkappa B and MAP kinase is through an interleukin-1 receptor-associated kinase (IRAK)-independent pathway employing the signaling components TLR3-TRAF6-TAK1-TAB2-PKR
    Zhengfan Jiang
    Department of Immunology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    J Biol Chem 278:16713-9. 2003
    ..share signaling components that associate with the IL-1 receptor, including IL-1 receptor-associated kinase (IRAK), MyD88, and TRAF6...
  96. doi TRAF6 is a critical signal transducer in IL-33 signaling pathway
    Megumi Funakoshi-Tago
    Department of Biochemistry, Kyoritsu University of Pharmacy, 1 5 30 Shibakoen, Minato ku, Tokyo 105 8512, Japan
    Cell Signal 20:1679-86. 2008
    ..IL-33 rapidly induced the formation of ST2L complex containing IL-1 receptor-associated kinase (IRAK), however, lack of TRAF6 abolished the recruitment of IRAK to ST2L...
  97. doi Adaptor proteins and Ras synergistically regulate IL-1-induced ADAMTS-4 expression in human chondrocytes
    Rasheed Ahmad
    Department of Medicine, University of Montreal and Centre de Recherche du Centre Hospitalier de l Université de Montréal, Notre Dame Hospital, Montreal, Quebec, Canada
    J Immunol 182:5081-7. 2009
    ..Thus, complete ablation of ADAMTS-4 induction could be achieved by combined inhibition of Ras and individual adaptor proteins, which may be of therapeutic value in arthritis...
  98. ncbi Severe impairment of interleukin-1 and Toll-like receptor signalling in mice lacking IRAK-4
    Nobutaka Suzuki
    Amgen Institute, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, 620 University Avenue, Suite 706, Toronto, Ontario M5G 2C1, Canada
    Nature 416:750-6. 2002
    ..Here we show by gene-targeting that IRAK-4, an IRAK molecule closely related to the Drosophila Pelle protein, is indispensable for the responses of animals and cultured cells to IL-1 and ligands that stimulate ..
  99. ncbi IRAK-4 as the central TIR signaling mediator in innate immunity
    Nobutaka Suzuki
    Ontario Cancer Institute and Dept of Medical Biophysics, University of Toronto 620 University Avenue, Ontario, M5G 2C1, Toronto, Canada
    Trends Immunol 23:503-6. 2002
    ..Signaling between MyD88 and TRAF6 is mediated by members of the IL-1R-associated kinase (IRAK) family; however, the exact function of each IRAK protein remains controversial...
  100. ncbi Ubiquitin activated tumor necrosis factor receptor associated factor-6 (TRAF6) is recycled via deubiquitination
    Liselotte E Jensen
    Department of Pharmacology and Center for Pharmacogenetics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6084, USA
    FEBS Lett 553:190-4. 2003
    ..This indicates a unique mechanism of regulation of TRAF6 activity...
  101. ncbi Ras participates in CpG oligodeoxynucleotide signaling through association with toll-like receptor 9 and promotion of interleukin-1 receptor-associated kinase/tumor necrosis factor receptor-associated factor 6 complex formation in macrophages
    Hongmei Xu
    Institute of Immunology, Second Military Medical University, Shanghai 200433, People s Republic of China
    J Biol Chem 278:36334-40. 2003
    ..which activates mitogen-activated protein kinases (MAPKs) and nuclear factor-kappaB (NF-kappaB) through the MyD88/IRAK/TRAF6 kinases cascade...

Research Grants70

  1. FUNCTIONAL ANALYSIS OF THE MOUSE-PELLE-LIKE KINASE
    Maureen Harrington; Fiscal Year: 2003
    ..defined components of a signaling pathway for Dorsal activation, including a serine/threonine protein kinases, Pelle, upstream of Dorsal and Cactus...
  2. EPITHELIAL CELL CYTOKINE SECRETION BY INTEGRINS
    Dennis McGee; Fiscal Year: 2005
    ..2) the role of TRAF6 in the suppression of the IL-1 intracellular signaling pathway, and (3) the effect on IRAK-1 and IRAK- 4...
  3. TLR-mediated Signaling Complex Formation and Regulation of Effector Functions
    Hans Haecker; Fiscal Year: 2012
    ..TLR activation leads to recruitment and oligomerization of the adaptor protein MyD88, which binds to members of the IRAK family, which in turn recruit TRAF6...
  4. Yong Jun Liu; Fiscal Year: 2014
    ..The third aim will focus on further characterization of three potential PACSIN1-interacting molecules including CD2AP, MEKK4 and TRAF4. ..
  5. Walter J Lukiw; Fiscal Year: 2016
    ..of at least three major mRNA targets, complement factor H (CFH), interleukin-1 receptor associated kinase (IRAK) and tetraspanin 12 (TSPAN12), that encode key modulators of the brain's innate immune system, inflammatory ..
  6. Kun Ping Lu; Fiscal Year: 2015
    ..These studies would uncover a novel mechanism in asthma development, and also could lead to more effective therapies because Pin1 inhibitors, especially when inhaled, might inhibit multiple targets in different cells in asthma. ..
  7. The novel role and regulation of IRAK in innate immunity
    Liwu Li; Fiscal Year: 2010
    ..Aim2 will examine the mechanism for IRAK1 mediated IL-10 gene expression. Aim3 will study the effect of IRAK1 deletion on the pathogenesis and/or resolution of atherosclerosis. ..
  8. FOXP3-microRNA146-NFkB Axis in Tumor Suppression
    Lizhong Wang; Fiscal Year: 2013
    ..abstract_text> ..
  9. Structural biology of Toll like receptor/IL 1R signaling
    Liang Tong; Fiscal Year: 2005
    ..pathway of the TLRs and IL-1RS involves many molecules, such as the adapter molecule MyD88, the protein kinase IRAK, TRAF6, and other down-stream mediators. MyD88 is a cytoplasmic protein and it also contains a TIR domain...
  10. Role of Pellino1 in liver inflammation
    Liselotte E Jensen; Fiscal Year: 2010
    ..An improved understanding of liver inflammation and the associated molecular pathways may facilitate the development of novel therapies for hepatitis and liver cancer. ..
  11. Regulation of signaling events in septic leukocytes
    Liwu Li; Fiscal Year: 2006
    ..We observe that the interleukin-1 receptor-associated kinase (IRAK), which lies proximal in the LPS-TLR signaling pathway, is inactivated and reduced in quantity upon prolonged LPS ..
  12. X chromosome, injury and infection
    Zoltan Spolarics; Fiscal Year: 2012
    ..Better understanding of the protecting cellular mechanisms that are in effect during septic conditions could lead to advanced protocols in treating the critically ill. ..
  13. Regulation of Tumor Associated Macrophages by TGF-beta
    Venkateshwar G Keshamouni; Fiscal Year: 2012
    ..b>IRAK-M is an inactive ser/thr kinase, potent negative regulator of TLR signaling and predominantly expressed in ..
  14. Andrei E Medvedev; Fiscal Year: 2014
    ..activation of TBK1 and transcription factor IRF-3;and (iv) increased expression of negative regulators Tollip, IRAK-M, SHIP-1, SOCS-1, SARM, and SIKE...
  15. Ceramide and acute phase protein elevation during aging
    Mariana Nikolova Karakashian; Fiscal Year: 2009
    ..the interactions between key molecules in the two cascades PI3K, Akt-1, and Foxo1 (for insulin), and ceramide, IRAK-1 and JNK (for IL-1β). Studies will be done in isolated hepatocytes in vitro and in animals in vivo...
  16. Stefanie N Vogel; Fiscal Year: 2014
    ..Our findings will lead to development of new drugs that will increase the capacity of macrophages to kill bacteria and viruses more effectively or to prevent or repair damage to tissues caused by bacterial or viral infection. ..
  17. Age-associated Toll-like receptor dysfunction in the lungs
    Carlos J Orihuela; Fiscal Year: 2010
    ..FACs analysis we will determine if mRNA and protein levels of TLRs 1-9, and the TLR cell signaling molecules Myd88, IRAK-1, and IRAK-4 are decreased in alveolar macrophages and type II pneumocytes (lung mucosal epithelial cells) ..
  18. Redox Mediated Signaling in the Toll-like Receptor Family
    FREDRICK OAKLEY; Fiscal Year: 2010
    ..IL-1R1 and TLR-4 share many similar effectors (MyD88, IRAK, TRAF6), but also have unique effectors (TIRAP/Mal, TRAM, TRIP), that specify unique biological properties of each ..
  19. Enhancing TB vaccine with gene silencing
    Jinhee Lee; Fiscal Year: 2013
    ..g. PDL1 and PDL2), and intracellular signaling regulators (e.g. SOCS1, SOCS2, and IRAK-M)...
  20. JASON LEE SPERRY; Fiscal Year: 2014
    ..will investigate a known functional X-linked polymorphism of the TLR pathway (IL-1 receptor-associated kinase-1, IRAK-1), while Aim#3 will characterize polymorphisms of the remaining two X-linked, TLR pathway constituents (Bruton&..
  21. Suman Jayadev; Fiscal Year: 2015
    ..with decreased levels of miR146a/b and increased levels of the miR146a target, the inflammatory signaling molecule, IRAK-1...
  22. Pranoti Mandrekar; Fiscal Year: 2016
    ..cytokine production by: A) Studying the interactions of MyD88- depepndent down-stream signaling molecules, IRAK-1 and IKK with co-chaperone cdc37 and hsp90 in alcoholic Kupffer cells and whole livers...
  23. Are the effects of SIMPL on hematopoiesis seen in vitro translated in vivo?
    Maureen Harrington; Fiscal Year: 2009
    ..TNFa activation of the mouse pelle-like kinase [mPLK;also known as the interleukin-1 receptor associated kinase (IRAK 1)] leads to phosphorylation and nuclear relocalization of SIMPL...
  24. IL-1 RECEPTORS AND CUTANEOUS DISEASE
    Thomas Kupper; Fiscal Year: 2003
    ..and the human Toll homolog was recently shown to signal through the interleukin-1 receptor-associated kinase (IRAK), indicating that human Toll and IL-1 share a common signaling pathway...
  25. IRAK Family Function in Bacterial Infection
    James Thomas; Fiscal Year: 2001
    ..This conserved signaling cascade consists of the proteins MyD88, the interleukin-1 receptor-associated kinase (IRAK) family of molecules (IRAK, IRAK2, and IRAK-M) and the tumor necrosis factor associated factor 6...
  26. John Y Kao; Fiscal Year: 2015
    ..Therefore, we hypothesize that H. pylori triggers a host tolerogenic response by interacting with DCs via a IRAK-M-mediated, TGF-2-dependent mechanism which alters the H...
  27. Juan C Salazar; Fiscal Year: 2015
    ..to Borrelia burgdorferi both in vitro and in vivo using human monocytes and macrophages obtained from children and adults with known congenital deficiencies in components of the MyD88 signaling pathway (IRAK-4 and MyD88 deficient).
  28. Nikolaos G Frangogiannis; Fiscal Year: 2016
    ..innate immune response in the infarcted myocardium: 1) We have identified Interleukin Receptor Associated Kinase (IRAK)-M, a member of the IRAK-M family that lacks kinase activity, as a key intracellular signal that is upregulated ..
  29. David Gate; Fiscal Year: 2014
    ..TLRs transduce their signals through the serine/threonine IL-1 receptor-associated kinase (IRAK)...
  30. EFFECT OF COLOSTRUM ON GUT MATURATION AND HOST DEFENSE
    W Allan Walker; Fiscal Year: 2013
    ..In addition, the cellular inhibitors of TLR-induced inflammation (SIGIRR, IRAK-M, Tollip, A-20 etc) are underexpressed, another possible cause of excessive inflammation...
  31. Role of IRAK-M in sepsis-induced immunosuppression
    Jane C Deng; Fiscal Year: 2010
    ..pathogens and the generation of an inflammatory innate immune response, lnterleukin-1 receptor associated kinase-M (IRAK-M) has been demonstrated to be a negative regulator of several TLRs, including TLR4, which is the receptor for ..
  32. Mariana Nikolova-Karakashian; Fiscal Year: 2015
    ..the interactions between key molecules in the two cascades PI3K, Akt-1, and Foxo1 (for insulin), and ceramide, IRAK-1 and JNK (for IL-12). Studies will be done in isolated hepatocytes in vitro and in animals in vivo...
  33. Liwu Li; Fiscal Year: 2016
    ..we demonstrated that low dose LPS selectively represses nuclear receptors including RARa through SRC-3, in an IRAK-1 and Tollip dependent pathway...
  34. Amr H Sawalha; Fiscal Year: 2016
    ..We will resequence the MECP2/IRAK1 LD block using next generation sequencing to identify the causal variants in this locus. ..
  35. The impact of Helicobacter pylori infection on inflammatory bowel disease suscept
    John Kao; Fiscal Year: 2009
    ..1.2. To examine the role of TLR-2 signaling and IRAK-M. Using TLR-2 null or IRAK-M siRNA to assess the role of these two pathways in H. pylori-induced DC tolerance. 2...
  36. Chaim O Jacob; Fiscal Year: 2014
    ..The discovery and characterization of the genetic factors which are the goals of this study are crucial for the understanding of the pathology of the disease and will result in novel targets and therapies for this devastating condition. ..
  37. Novel Therapy for Sepsis
    Dale Christensen; Fiscal Year: 2007
    ..levels (serum TNFa, Il-1?, IL-6 levels), clotting times and activation of cell signaling (phospho-JNK, phospho-IRAK, phospho-P38)...
  38. Characterization of mutants affected in innate immunity
    Katrina Ramonell; Fiscal Year: 2005
    ..g., Toll-like receptors, pelle-like kinases, ankyrin-repeat containing proteins), there is precedence to suggest that some signaling pathways in ..
  39. The LPS Responsiveness of TLR2 an TLR4 in the Neutrophil
    PATRICK ARNDT; Fiscal Year: 2005
    ..responsible for LPS induced NF-KB and/or p38 activation in the neutrophil with the signaling pathway involving IRAK 2 and M, syk and Rac2...
  40. IL-1 RECEPTOR MEDIATED SIGNAL TRANSDUCTION
    PHILIP AURON; Fiscal Year: 2003
    ..that the activation of the transcription factor NF-kappaB depends not only upon the previously characterized IRAK pathway, but also a novel independent pathway involving IL-1 receptor tyrosine phosphorylation and recruitment and ..
  41. Innate Immunity, HIV, and OIs: Role of TLRs in the Lung
    Paul Skolnik; Fiscal Year: 2004
    ..TLR2- and TLR4-mediated TNFc_ production; (iii) phosphorylated signaling intermediaries of the TLR pathway (MyD88, IRAK, and PI3'-kinase), and concomitant NF-kB DNA-binding activity; and (iv) if HW-1 gp120 or gp160 affect TLR2 or TLR4 ..
  42. MOLECULAR PATHOGENESIS OF CARDIAC DYSFUNCTION
    Brett Giroir; Fiscal Year: 2004
    ..transgenic animals to mice which have undergone targeted disruption of iNOS (inducible nitric oxide synthase), IRAK (IL-1 receptor associated kinase), and ICAM-1 / P-selectin, as well as by pharmacological inhibition of specific ..
  43. TOLL RECEPTOR ACTIVATION OF NF-kB IN INSULIN RESISTANCE AND T2DM
    Steven E Shoelson; Fiscal Year: 2010
    ..MyD88, IRAK4 and IRAK-M in particular provide an opportunity to investigate this large field by manipulating only three key proteins...
  44. CIAS1, A Regulator of NF-kB Activity and Inflammation
    WILLIE BRICKEY; Fiscal Year: 2005
    ..This is reminiscent of the recently described IRAK-M molecule, which is a negative regulator of endotoxin response and is induced by TLR agonist...
  45. FUNCTION OF NORMAL AND MALIGNANT PHAGOCYTES
    SERGIO CATZ; Fiscal Year: 2007
    ..Several studies on phosphorylation will be carried out, including one on IRAK-4. An examination of the PX domain of p47PHOX will be undertaken...
  46. IMMUNOMODULATION OF MACROPHAGES FOLLOWING TRAUMA
    Ronald Maier; Fiscal Year: 2006
    ..MAPK family) to varying stimuli and cell specificity; 2) investigate signal initiation processes (including TLR-4, IRAK and PYK-2) and the need for an intact cytoskeleton; 3) identify potential response regulators, including CaMK, PKA ..
  47. SIGIRR A Negative Regulator of Toll-IL-IR Signaling
    Xiaoxia Li; Fiscal Year: 2009
    ..Specifically, the proposed studies should result in significant advances in the field of innate mucosal immunity and should also help us to determine the potential of SIGIRR as a target for developing anti-inflammatory drugs. ..
  48. Molecular Mechanisms of IL-1R-TLR-Mediated Signaling
    Xiaoxia Li; Fiscal Year: 2008
    ..The long-term objective is to develop more effective anti-inflammatory and anti-atherogenic small molecule drugs. [unreadable] [unreadable] [unreadable]..
  49. Molecular Mechanisms for IL-25-mediated Th2 Responses
    Xiaoxia Li; Fiscal Year: 2010
    ..With this improved understanding comes the potential to develop specific inhibitors of these pathways and perhaps novel therapeutics for the treatment of asthma. ..
  50. IRAK Family Function in Bacterial Infection
    James Thomas; Fiscal Year: 2006
    ..This conserved signaling cascade consists of the proteins MyD88, the interleukin-1 receptor-associated kinase (IRAK) family of molecules (IRAK, IRAK2, and IRAK-M) and the tumor necrosis factor associated factor 6...
  51. A new direction in studing sex hormone involovement in *
    Chaim Jacob; Fiscal Year: 2003
    ..Stanczyk) and biochemistry of steroid hormones (Dr. Roberts). The project proposed represents a clear and distinct departure from the PI's and the other investigators ongoing research. ..
  52. GENETICS OF CHILDHOOD ONSET SLE
    Chaim Jacob; Fiscal Year: 2003
    ..They further state that this is a multi-center application from some of the largest pediatric lupus clinics in the country and, therefore, represents a major and unique resource for the study of the genetics of childhood-onset SLE. ..
  53. Cytokine mechanisms in systemic lupus erythematosus
    Chaim Jacob; Fiscal Year: 2008
    ..These studies should lead to better understanding of a number of characteristics of SLE and may lead to identification of new targets for therapy. ..
  54. Act1 in CD40-/BAFFR-Mediated B Cell Survival
    Xiaoxia Li; Fiscal Year: 2009
    ..These findings will help us to elucidate the detailed regulatory mechanism for B cell homeostasis and opens new possibility to intervene the immune system. ..
  55. FOUR DIMENSIONAL IMAGING OF THE IMMUNE RESPONSE IN VIVO
    James T Rosenbaum; Fiscal Year: 2010
    ..These studies should result in a fundamental improvement in the understanding of how T cells behave within a site of inflammation. ..
  56. Respiratory Immunity Against Agents of Bioterrorism
    STEVEN MIZEL; Fiscal Year: 2008
    ....
  57. PGE2 Regulation of Epithelial/Fibroblast Interactions
    Bethany Moore; Fiscal Year: 2006
    ..abstract_text> ..
  58. Mechanisms and Consequences of Toll Like Receptor Signal Transduction
    Stefanie Vogel; Fiscal Year: 2008
    ..3) Assess the mechanism of TLR tyrosine phosphorylation and its functional consequences. ..
  59. Heat shock proteins and alcohol induced liver injury
    Pranoti Mandrekar; Fiscal Year: 2006
    ....
  60. ROLES OF TOLL LIKE RECEPTORS IN INNATE IMMUNITY
    Stefanie Vogel; Fiscal Year: 2005
    ....
  61. Anterior Uveal Dendritic Cells
    James Rosenbaum; Fiscal Year: 2004
    ..These studies will clarify the function of the immune system within the eye and may suggest novel therapeutic approaches in the treatment of uveitis. ..
  62. EARLY ENDOTOXIN TOLERANCE: CELLULAR/MOLECULAR MECHANISMS
    Stefanie Vogel; Fiscal Year: 2004
    ..It is expected that, at the conclusion of this research, the mechanism of endotoxin tolerance and its potential impact on disease outcome in both sepsis and other diseases will be better understood. ..
  63. IMMUNOLOGY/MOLECULAR BIOLOGY TRAINING IN OPHTHALMOLOGY
    James Rosenbaum; Fiscal Year: 2007
    ..The quality of the institution, the talents of the specific faculty, the abilities of the applicant pool, and the proven success of the program areadditional strengths of this application. ..
  64. UVEITIS GENE-EXPRESSION PROFILING
    James Rosenbaum; Fiscal Year: 2008
    ..The creation of a gene expression data base for patients with uveitis has the potential to clarify the pathogenesis of disease, establish new diagnostic tools, and provide a means for predicting prognosis. ..
  65. CHEMOTACTIC FACTORS IN ANIMAL MODELS OF UVEITIS
    James Rosenbaum; Fiscal Year: 2008
    ..We believe that these aims are novel, innovative, especially suited to the skills and achievements demonstrated by our laboratory, and highly relevant to clarifying the pathogenesis of anterior uveitis. ..
  66. Structural Studies of the Innate Immune Pathway
    MICHAEL LASKER; Fiscal Year: 2008
    ....
  67. Antibacterial peptidoglycan recognition proteins
    Roman Dziarski; Fiscal Year: 2007
    ..abstract_text> ..
  68. Activation of inflammatory cells by flagellin
    STEVEN MIZEL; Fiscal Year: 2006
    ..This lack of responsiveness is associated with a dramatic decrease in IRAK kinase activity. This decrease in IRAK activity is not due to a decrease in the level of the IRAK protein...
  69. ROLE OF IGF-I IN PREVENTING CARDIOMYOCYTE APOPTOSIS
    Wei Chao; Fiscal Year: 2005
    ..abstract_text> ..
  70. CXC CHEMOKINE REGULATION OF PROSTATE CANCER ANGIOGENESIS
    Bethany Moore; Fiscal Year: 2002
    ..These studies should lead to new insights into the biology of prostate cancer growth and metastasis, and pave the way to adapt adjuvant therapies for the treatment of this widespread disease. ..