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
Products:     IRAK

Top Publications

  1. Mamidipudi V, Lin C, Seibenhener M, Wooten M. Regulation of interleukin receptor-associated kinase (IRAK) phosphorylation and signaling by iota protein kinase C. J Biol Chem. 2004;279:4161-5 pubmed
    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)...
  2. Jacinto R, Hartung T, McCall C, Li L. Lipopolysaccharide- and lipoteichoic acid-induced tolerance and cross-tolerance: distinct alterations in IL-1 receptor-associated kinase. J Immunol. 2002;168:6136-41 pubmed
    ..We observe that down-regulation of IL-1R-associated kinase (IRAK) protein level and kinase activity closely correlates with the development of cross-tolerance...
  3. Chiang E, Yu X, Grogan J. 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. J Immunol. 2011;186:1279-88 pubmed publisher
    ..These data reveal important species differences and elaborate cell type requirements for IRAK1/4 kinase activity. ..
  4. Cao Z, Henzel W, Gao X. IRAK: a kinase associated with the interleukin-1 receptor. Science. 1996;271:1128-31 pubmed
    ..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.
  5. Qian Y, Commane M, Ninomiya Tsuji J, Matsumoto K, Li X. IRAK-mediated translocation of TRAF6 and TAB2 in the interleukin-1-induced activation of NFkappa B. J Biol Chem. 2001;276:41661-7 pubmed
    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...
  6. Brissoni B, Agostini L, Kropf M, Martinon F, Swoboda V, Lippens S, et al. Intracellular trafficking of interleukin-1 receptor I requires Tollip. Curr Biol. 2006;16:2265-70 pubmed
    ..Our findings suggest that Tollip functions as an endosomal adaptor linking IL-1RI, via Tom1, to the endosomal degradation machinery. ..
  7. Uematsu S, Sato S, Yamamoto M, Hirotani T, Kato H, Takeshita F, et al. Interleukin-1 receptor-associated kinase-1 plays an essential role for Toll-like receptor (TLR)7- and TLR9-mediated interferon-{alpha} induction. J Exp Med. 2005;201:915-23 pubmed
    ..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...
  8. Ordureau A, Smith H, Windheim M, Peggie M, Carrick E, Morrice N, et al. The IRAK-catalysed activation of the E3 ligase function of Pellino isoforms induces the Lys63-linked polyubiquitination of IRAK1. Biochem J. 2008;409:43-52 pubmed
    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...
  9. Li S, Strelow A, Fontana E, Wesche H. IRAK-4: a novel member of the IRAK family with the properties of an IRAK-kinase. Proc Natl Acad Sci U S A. 2002;99:5567-72 pubmed
    ..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 ..

More Information


  1. Burns K, Clatworthy J, Martin L, Martinon F, Plumpton C, Maschera B, et al. Tollip, a new component of the IL-1RI pathway, links IRAK to the IL-1 receptor. Nat Cell Biol. 2000;2:346-51 pubmed
    ..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...
  2. Conze D, Wu C, Thomas J, Landstrom A, Ashwell J. Lys63-linked polyubiquitination of IRAK-1 is required for interleukin-1 receptor- and toll-like receptor-mediated NF-kappaB activation. Mol Cell Biol. 2008;28:3538-47 pubmed publisher
    ..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...
  3. Kollewe C, Mackensen A, Neumann D, Knop J, Cao P, Li S, et al. Sequential autophosphorylation steps in the interleukin-1 receptor-associated kinase-1 regulate its availability as an adapter in interleukin-1 signaling. J Biol Chem. 2004;279:5227-36 pubmed
    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...
  4. Li X, Commane M, Jiang Z, Stark G. IL-1-induced NFkappa B and c-Jun N-terminal kinase (JNK) activation diverge at IL-1 receptor-associated kinase (IRAK). Proc Natl Acad Sci U S A. 2001;98:4461-5 pubmed
    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...
  5. Jiang Z, Ninomiya Tsuji J, Qian Y, Matsumoto K, Li X. 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. Mol Cell Biol. 2002;22:7158-67 pubmed
    Interleukin-1 (IL-1) receptor-associated kinase (IRAK) plays an important role in the sequential formation and activation of IL-1-induced signaling complexes...
  6. Cao Z, Xiong J, Takeuchi M, Kurama T, Goeddel D. TRAF6 is a signal transducer for interleukin-1. Nature. 1996;383:443-6 pubmed
    ..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...
  7. Qin J, Jiang Z, Qian Y, Casanova J, Li X. IRAK4 kinase activity is redundant for interleukin-1 (IL-1) receptor-associated kinase phosphorylation and IL-1 responsiveness. J Biol Chem. 2004;279:26748-53 pubmed
    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...
  8. Wesche H, Gao X, Li X, Kirschning C, Stark G, Cao Z. IRAK-M is a novel member of the Pelle/interleukin-1 receptor-associated kinase (IRAK) family. J Biol Chem. 1999;274:19403-10 pubmed
    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...
  9. Lee J, Lee H, Lee E, Jang S, Kim H, Yoon J, et al. Down syndrome candidate region-1 protein interacts with Tollip and positively modulates interleukin-1 receptor-mediated signaling. Biochim Biophys Acta. 2009;1790:1673-80 pubmed publisher
    ..IL-1R)-mediated signaling by analyzing interaction between DSCR1-1S and the IL-1R pathway components Tollip, IRAK-1, and TRAF6...
  10. Muzio M, Ni J, Feng P, Dixit V. IRAK (Pelle) family member IRAK-2 and MyD88 as proximal mediators of IL-1 signaling. Science. 1997;278:1612-5 pubmed 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-..
  11. Burns K, Janssens S, Brissoni B, Olivos N, Beyaert R, Tschopp J. 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. J Exp Med. 2003;197:263-8 pubmed
    ..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...
  12. Muzio M, Natoli G, Saccani S, Levrero M, Mantovani A. The human toll signaling pathway: divergence of nuclear factor kappaB and JNK/SAPK activation upstream of tumor necrosis factor receptor-associated factor 6 (TRAF6). J Exp Med. 1998;187:2097-101 pubmed
    ..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. ..
  13. Takaesu G, Ninomiya Tsuji J, Kishida S, Li X, Stark G, Matsumoto K. Interleukin-1 (IL-1) receptor-associated kinase leads to activation of TAK1 by inducing TAB2 translocation in the IL-1 signaling pathway. Mol Cell Biol. 2001;21:2475-84 pubmed
    ..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...
  14. Thomas J, Allen J, Tsen M, Dubnicoff T, Danao J, Liao X, et al. Impaired cytokine signaling in mice lacking the IL-1 receptor-associated kinase. J Immunol. 1999;163:978-84 pubmed
    ..type 1 IL-1R (IL-1R1) and the IL-18R by their cognate ligands induces recruitment of the IL-1R-associated kinase (IRAK)...
  15. Burns K, Martinon F, Esslinger C, Pahl H, Schneider P, Bodmer J, et al. MyD88, an adapter protein involved in interleukin-1 signaling. J Biol Chem. 1998;273:12203-9 pubmed
    ..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...
  16. Mizel S, Snipes J. Gram-negative flagellin-induced self-tolerance is associated with a block in interleukin-1 receptor-associated kinase release from toll-like receptor 5. J Biol Chem. 2002;277:22414-20 pubmed
    ..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...
  17. Medvedev A, Lentschat A, Wahl L, Golenbock D, Vogel S. Dysregulation of LPS-induced Toll-like receptor 4-MyD88 complex formation and IL-1 receptor-associated kinase 1 activation in endotoxin-tolerant cells. J Immunol. 2002;169:5209-16 pubmed
    ..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 ..
  18. Jefferies C, Doyle S, Brunner C, Dunne A, Brint E, Wietek C, et al. 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. J Biol Chem. 2003;278:26258-64 pubmed
    ..Our findings implicate Btk as a Toll/interleukin-1 receptor domain-binding protein that is important for NFkappaB activation by TLR4. ..
  19. Jacob C, Zhu J, Armstrong D, Yan M, Han J, Zhou X, et al. Identification of IRAK1 as a risk gene with critical role in the pathogenesis of systemic lupus erythematosus. Proc Natl Acad Sci U S A. 2009;106:6256-61 pubmed publisher
    ..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. ..
  20. Emmerich C, Ordureau A, Strickson S, Arthur J, Pedrioli P, Komander D, et al. Activation of the canonical IKK complex by K63/M1-linked hybrid ubiquitin chains. Proc Natl Acad Sci U S A. 2013;110:15247-52 pubmed publisher
    ..Interleukin-1 receptor (IL-1R)-associated kinase (IRAK) 1 is modified first by K63-pUb chains to which M1-pUb linkages are added subsequently, and myeloid differentiation ..
  21. DiDonato J, Hayakawa M, Rothwarf D, Zandi E, Karin M. A cytokine-responsive IkappaB kinase that activates the transcription factor NF-kappaB. Nature. 1997;388:548-54 pubmed
    ..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. ..
  22. Windheim M, Stafford M, Peggie M, Cohen P. 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. Mol Cell Biol. 2008;28:1783-91 pubmed publisher
    ..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. ..
  23. Xiao H, Qian W, Staschke K, Qian Y, Cui G, Deng L, et al. Pellino 3b negatively regulates interleukin-1-induced TAK1-dependent NF kappaB activation. J Biol Chem. 2008;283:14654-64 pubmed publisher
    IL-1 receptor-associated kinase (IRAK) is phosphorylated, ubiquitinated, and degraded upon interleukin-1 (IL-1) stimulation...
  24. Smith H, Peggie M, Campbell D, Vandermoere F, Carrick E, Cohen P. Identification of the phosphorylation sites on the E3 ubiquitin ligase Pellino that are critical for activation by IRAK1 and IRAK4. Proc Natl Acad Sci U S A. 2009;106:4584-90 pubmed publisher
    ..These observations imply that dephosphorylation of multiple sites is required to inactivate Pellino 1, which could be a device for prolonging Pellino's E3 ubiquitin ligase activity in vivo. ..
  25. Abe T, Kaname Y, Hamamoto I, Tsuda Y, Wen X, Taguwa S, et al. Hepatitis C virus nonstructural protein 5A modulates the toll-like receptor-MyD88-dependent signaling pathway in macrophage cell lines. J Virol. 2007;81:8953-66 pubmed
    ..These results suggest that the expression of HCV proteins modulates the TLR signaling pathway in immune cells. ..
  26. Hu J, Jacinto R, McCall C, Li L. Regulation of IL-1 receptor-associated kinases by lipopolysaccharide. J Immunol. 2002;168:3910-4 pubmed
    IL-1R-associated kinase (IRAK) plays a pivotal role in IL-1R/Toll-like receptor (TLR)-mediated signaling and NF-kappaB activation...
  27. Su B, Chen J. Antimicrobial Peptide Epinecidin-1 Modulates MyD88 Protein Levels via the Proteasome Degradation Pathway. Mar Drugs. 2017;15: pubmed publisher
    ..protein MyD88 or endogenous TLR signaling antagonists, which include A20, interleukin-1 receptor associated kinase (IRAK)-M, and suppressor of cytokine signaling (SOCS)-1...
  28. Li H, Zhang L, Chen L, Zhu Q, Wang W, Qiao J. Lactobacillus acidophilus alleviates the inflammatory response to enterotoxigenic Escherichia coli K88 via inhibition of the NF-?B and p38 mitogen-activated protein kinase signaling pathways in piglets. BMC Microbiol. 2016;16:273 pubmed
    ..acidophilus significantly increased the expression of the negative regulators of TLRs signaling, including Tollip, IRAK-M, A20 and Bcl-3 in spleen of ETEC-challenged piglets. Our findings suggested that L...
  29. Dong W, Liu Y, Peng J, Chen L, Zou T, Xiao H, et al. The IRAK-1-BCL10-MALT1-TRAF6-TAK1 cascade mediates signaling to NF-kappaB from Toll-like receptor 4. J Biol Chem. 2006;281:26029-40 pubmed
    ..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 ..
  30. Park J, Kim S, Kim Y, Yang W, Kim Y, Hong S, et al. Anti-Inflammatory and Antinociceptive Activities of Anthraquinone-2-Carboxylic Acid. Mediators Inflamm. 2016;2016:1903849 pubmed publisher
    ..Our data strongly suggest that anthraquinones such as AQCA act as potent anti-inflammatory and antinociceptive components in vivo, thus contributing to the immune regulatory role of fruits and herbs. ..
  31. Fu X, Lin Q, Liu L, Liang H, Huang Z, Li N. Display of ISKNV orf086 protein on the surface of Aeromonas hydrophila and its immunogenicity in Chinese perch (Siniperca chuatsi). Fish Shellfish Immunol. 2016;56:286-293 pubmed publisher
    ..hydrophila and suggests the possibility to use the recombinant K28 strain as a combined vaccine against ISKNV and A. hydrophila infection. ..
  32. Hui B, Zhang L, Zhou Q, Hui L. Pristimerin Inhibits LPS-Triggered Neurotoxicity in BV-2 Microglia Cells Through Modulating IRAK1/TRAF6/TAK1-Mediated NF-κB and AP-1 Signaling Pathways In Vitro. Neurotox Res. 2018;33:268-283 pubmed publisher
    ..These findings may suggest that pristimerin might serve as a new therapeutic agent for treating hyperactivated microglial induced neurodegenerative diseases. ..
  33. Zhang Y, Lin X, Desrosiers M, Zhang W, Meng N, Zhao L, et al. Association pattern of interleukin-1 receptor-associated kinase-4 gene polymorphisms with allergic rhinitis in a Han Chinese population. PLoS ONE. 2011;6:e21769 pubmed publisher
    Interleukin-1 receptor-associated kinase-4 (IRAK-4) encodes a kinase that is essential for NF-kB activation in Toll-like receptor and T-cell receptor signaling pathways, indicating a possible crosstalk between innate and acquired ..
  34. Wu C, Chen Y, Wang F, CHEN C, Zhang S, Li C, et al. Pelle Modulates dFoxO-Mediated Cell Death in Drosophila. PLoS Genet. 2015;11:e1005589 pubmed publisher
    ..b>Pelle is the sole Drosophila IRAK homolog implicated in the conserved Toll pathway that regulates Dorsal/Ventral ..
  35. Camprubí Rimblas M, Guillamat Prats R, Lebouvier T, Bringué J, Chimenti L, Iglesias M, et al. Role of heparin in pulmonary cell populations in an in-vitro model of acute lung injury. Respir Res. 2017;18:89 pubmed publisher
    ..Our results suggested that a local pulmonary administration of heparin through nebulization may be able to reduce inflammation in the lung; however, further studies are needed to confirm this hypothesis. ..
  36. Gan L, Li L. Interleukin-1 Receptor-Associated Kinase-1 (IRAK-1) functionally associates with PKCepsilon and VASP in the regulation of macrophage migration. Mol Immunol. 2010;47:1278-82 pubmed publisher
    ..the involvement of a key innate immunity signaling kinase, Interleukin-1 Receptor-Associated Kinase-1 (IRAK-1) as a critical modulator of macrophage migration...
  37. Yuan Y, Gong X, Zhang L, Jiang R, Yang J, Wang B, et al. Chlorogenic acid ameliorated concanavalin A-induced hepatitis by suppression of Toll-like receptor 4 signaling in mice. Int Immunopharmacol. 2017;44:97-104 pubmed publisher
  38. Cheng B, Lau E, Leung H, Leung C, Ho N, Gurung S, et al. IRAK1 Augments Cancer Stemness and Drug Resistance via the AP-1/AKR1B10 Signaling Cascade in Hepatocellular Carcinoma. Cancer Res. 2018;78:2332-2342 pubmed publisher
    ..of 16 pairs of clinical HCC samples, we report that interleukin-1 receptor-associated kinase 1 (IRAK1) in the TLR/IRAK pathway is significantly upregulated in HCC...
  39. Naik S, Padhi A, Ganguli G, Sengupta S, Pati S, Das D, et al. Mouse Bone Marrow Sca-1+ CD44+ Mesenchymal Stem Cells Kill Avirulent Mycobacteria but Not Mycobacterium tuberculosis through Modulation of Cathelicidin Expression via the p38 Mitogen-Activated Protein Kinase-Dependent Pathway. Infect Immun. 2017;85: pubmed publisher
    ..Further downstream investigations demonstrated that IRAK-4-p38 activation increased the nuclear translocation of NF-?B, which subsequently induced the expression of ..
  40. Wang Y, Chen L, Tian Z, Shen X, Wang X, Wu H, et al. CRISPR-Cas9 mediated gene knockout in human coronary artery endothelial cells reveals a pro-inflammatory role of TLR2. Cell Biol Int. 2018;42:187-193 pubmed publisher
    ..The expression status of myeloid differentiation primary response gene 88 (MyD88), phosphorylated IRAK-1 (pIRAK-1) and phosphorylated NF-?B (pNF-?B) were detected by Western blot...
  41. Chen Y, Wu Z, Yuan B, Dong Y, Zhang L, Zeng Z. MicroRNA-146a-5p attenuates irradiation-induced and LPS-induced hepatic stellate cell activation and hepatocyte apoptosis through inhibition of TLR4 pathway. Cell Death Dis. 2018;9:22 pubmed publisher
    ..Collectively, this study reveals the anti-pro-inflammatory and anti-fibrotic effects of miR-146a-5p on liver injury, and suggests a potential application of miR-146a-5p in the therapeutic prevention of RILD. ..
  42. Yi Z, Pan H, Li L, Wu H, Wang S, Ma Y, et al. Chromosome Xq28 duplication encompassing MECP2: Clinical and molecular analysis of 16 new patients from 10 families in China. Eur J Med Genet. 2016;59:347-53 pubmed publisher
  43. Williams K, Lich J, Duncan J, Reed W, Rallabhandi P, Moore C, et al. The CATERPILLER protein monarch-1 is an antagonist of toll-like receptor-, tumor necrosis factor alpha-, and Mycobacterium tuberculosis-induced pro-inflammatory signals. J Biol Chem. 2005;280:39914-24 pubmed
    ..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 ..
  44. Chen J, Shi X, Zhang X, Wang A, Wang L, Yang Y, et al. MicroRNA 373 Facilitates the Replication of Porcine Reproductive and Respiratory Syndrome Virus by Its Negative Regulation of Type I Interferon Induction. J Virol. 2017;91: pubmed publisher
    ..In conclusion, this paper revealed a novel mechanism of PRRSV that impaired the production of type I IFN by upregulating miR-373 expression in MARC-145 cells. ..
  45. Nguyen T, De Nardo D, Masendycz P, Hamilton J, Scholz G. Regulation of IRAK-1 activation by its C-terminal domain. Cell Signal. 2009;21:719-26 pubmed publisher
    ..Toll-like receptors (TLRs) are largely responsible for meditating the activation of macrophages by pathogens. IRAK-1 is a proximal protein kinase in TLR signalling pathways and hence its activation must be tightly regulated...
  46. Ling L, Goeddel D. T6BP, a TRAF6-interacting protein involved in IL-1 signaling. Proc Natl Acad Sci U S A. 2000;97:9567-72 pubmed
    ..Formation of the TRAF6-T6BP complex depends on the presence of the IL-1 receptor-associated kinase (IRAK)...
  47. Jiang K, Ma X, Guo S, Zhang T, Zhao G, Wu H, et al. Anti-inflammatory Effects of Rosmarinic Acid in Lipopolysaccharide-Induced Mastitis in Mice. Inflammation. 2018;41:437-448 pubmed publisher
    ..In addition, RA was also found to inhibit LPS-induced NF-κB signaling pathway activation. These results suggest that RA effectively attenuates LPS-induced mastitis by inhibiting the TLR4/MyD88/NF-κB signaling pathway. ..
  48. Grazioli S, Hamilton S, McKinnon M, Del Bel K, Hoang L, Cook V, et al. IRAK-4 deficiency as a cause for familial fatal invasive infection by Streptococcus pneumoniae. Clin Immunol. 2016;163:14-6 pubmed publisher the Editor we report the case of two siblings with fatal pneumococcal meningitis as the initial manifestation of IRAK-4 deficiency caused by previously undescribed mutations in IRAK4...
  49. Heiseke A, Jeuk B, Markota A, Straub T, Lehr H, Reindl W, et al. IRAK1 Drives Intestinal Inflammation by Promoting the Generation of Effector Th Cells with Optimal Gut-Homing Capacity. J Immunol. 2015;195:5787-94 pubmed publisher
    IL-1R-associated kinase (IRAK) 1 is an important component of the IL-1R and TLR signaling pathways, which influence Th cell differentiation...
  50. Greenwood A, Kwon J, Nicholson L. Isomerase-catalyzed binding of interleukin-1 receptor-associated kinase 1 to the EVH1 domain of vasodilator-stimulated phosphoprotein. Biochemistry. 2014;53:3593-607 pubmed publisher
    ..These studies demonstrate a direct interaction between IRAK1 and VASP and suggest a potential mechanism for how this interaction might be regulated by both assembly of IRAK1 onto an activated signaling complex and PPIase enzymes. ..
  51. Chen Y, Chen J, Wang H, Shi J, Wu K, Liu S, et al. HCV-induced miR-21 contributes to evasion of host immune system by targeting MyD88 and IRAK1. PLoS Pathog. 2013;9:e1003248 pubmed publisher
    ..Taken together, our results indicate that miR-21 is upregulated during HCV infection and negatively regulates IFN-? signaling through MyD88 and IRAK1 and may be a potential therapeutic target for antiviral intervention. ..
  52. Song G, Bae S, Seo Y, Kim J, Choi S, Ji J, et al. The association between susceptibility to inflammatory arthritis and miR-146a, miR-499 and IRAK1 polymorphisms. A meta-analysis. Z Rheumatol. 2015;74:637-45 pubmed publisher
    ..This meta-analysis suggests that the miR-499 rs374644 and IRAKI rs3027898 polymorphisms are associated with susceptibility to inflammatory arthritis. ..
  53. Rosati O, Martin M. Identification and characterization of murine IRAK-M. Biochem Biophys Res Commun. 2002;293:1472-7 pubmed
    ..Today four different human IRAKs (hu-IRAK-1, hu-IRAK-2, hu-IRAK-M, hu-IRAK-4) and two murine IRAKs (mouse pelle like kinase (mPLK) and mu-IRAK-4) have been described...
  54. Yagasaki Y, Sudo T, Osada H. Exip, a splicing variant of p38alpha, participates in interleukin-1 receptor proximal complex and downregulates NF-kappaB pathway. FEBS Lett. 2004;575:136-40 pubmed
    ..Together, these results demonstrate that Exip can be a new component of NF-kappaB pathway, and contribute to a comprehensive understanding of the signal transduction pathway in the inflammatory responses. ..
  55. Bol G, Kreuzer O, Brigelius Flohe R. Translocation of the interleukin-1 receptor-associated kinase-1 (IRAK-1) into the nucleus. FEBS Lett. 2000;477:73-8 pubmed
    Interleukin-1 (IL-1) signal transduction involves the recruitment of the IL-1 receptor-associated kinase-1 (IRAK-1). Subsequent signaling finally leads to nuclear translocation of NFkappaB...
  56. Lei L, Wang W, Xia C, Liu F. Salmonella Virulence Factor SsrAB Regulated Factor Modulates Inflammatory Responses by Enhancing the Activation of NF-κB Signaling Pathway. J Immunol. 2016;196:792-802 pubmed publisher
    ..SrfA was secreted into the cytoplasm during S. Typhimurium infection and disassociated IL-1R-associated kinase-1 (IRAK-1) from the IRAK-1-Toll interacting protein (Tollip) complex by interacting with Tollip...
  57. Tun Kyi A, Finn G, Greenwood A, Nowak M, Lee T, Asara J, et al. Essential role for the prolyl isomerase Pin1 in Toll-like receptor signaling and type I interferon-mediated immunity. Nat Immunol. 2011;12:733-41 pubmed publisher
    ..Given the critical role of aberrant activation of IRAK1 and type I interferons in various immune diseases, controlling IRAK1 activation via inhibition of Pin1 may represent a useful therapeutic approach. ..
  58. Khalifa O, Balandraud N, Lambert N, Auger I, Roudier J, Sénéchal A, et al. TMEM187-IRAK1 Polymorphisms Associated with Rheumatoid Arthritis Susceptibility in Tunisian and French Female Populations: Influence of Geographic Origin. J Immunol Res. 2017;2017:4915950 pubmed publisher
    ..Our data further support the involvement of X chromosome in RA susceptibility and evidence ethnicities differences that might be explained by differences in the frequencies of SE HLA-DRB1 alleles between both populations. ..
  59. Samuels T, Yan J, Khampang P, Mackinnon A, Hong W, Johnston N, et al. Association of microRNA 146 with middle ear hyperplasia in pediatric otitis media. Int J Pediatr Otorhinolaryngol. 2016;88:104-8 pubmed publisher
    ..This report is the first to assess miRNA expression in a clinical population with OM. Findings herein suggest miR-146 may play a role in OM. ..
  60. Butler M, Hanly J, Moynagh P. Pellino3 is a novel upstream regulator of p38 MAPK and activates CREB in a p38-dependent manner. J Biol Chem. 2005;280:27759-68 pubmed
    ..Our study not only identifies Pellino3 as a novel upstream regulator of the p38 MAPK pathway but also probes the mechanistic basis underlying the ability of Pellino3 to promote activation of this pathway. ..
  61. Heinz L, Rebsamen M, Rossi D, Staehli F, Schroder K, Quadroni M, et al. The death domain-containing protein Unc5CL is a novel MyD88-independent activator of the pro-inflammatory IRAK signaling cascade. Cell Death Differ. 2012;19:722-31 pubmed publisher
    ..we show that the DD-containing protein Unc5CL (also known as ZUD) is involved in a novel MyD88-independent mode of IRAK signaling that culminates in the activation of the transcription factor nuclear factor kappa B (NF-?B) and c-Jun N-..
  62. Chen R, Li M, Zhang Y, Zhou Q, Shu H. The E3 ubiquitin ligase MARCH8 negatively regulates IL-1?-induced NF-?B activation by targeting the IL1RAP coreceptor for ubiquitination and degradation. Proc Natl Acad Sci U S A. 2012;109:14128-33 pubmed publisher
    ..Our findings suggest that MARCH8-mediated polyubiquitination and degradation of IL1RAP is an important mechanism for negative regulation of IL-1?-induced signaling pathways. ..
  63. Khursigara G, Orlinick J, Chao M. Association of the p75 neurotrophin receptor with TRAF6. J Biol Chem. 1999;274:2597-600 pubmed
    ..These results indicate that TRAF6 can potentially function as a signal transducer for NGF actions through the p75 receptor. ..
  64. Reichwald K, Thiesen J, Wiehe T, Weitzel J, Poustka W, Rosenthal A, et al. Comparative sequence analysis of the MECP2-locus in human and mouse reveals new transcribed regions. Mamm Genome. 2000;11:182-90 pubmed
    ..identified the MECP2/Mecp2 locus, which is flanked by the gene coding for Interleukin-1 receptor associated kinase (IRAK/Il1rak) and the red opsin gene (RCP/Rsvp)...
  65. Sampath V, Mulrooney N, Garland J, He J, Patel A, Cohen J, et al. Toll-like receptor genetic variants are associated with Gram-negative infections in VLBW infants. J Perinatol. 2013;33:772-7 pubmed publisher
    ..The TLR5 (rs5744105) variant was associated with elevated WBC counts during infections. TLR genetic variants can contribute to increased risk of bacterial infections and altered immune responses in VLBW infants. ..
  66. Huang J, Gao X, Li S, Cao Z. Recruitment of IRAK to the interleukin 1 receptor complex requires interleukin 1 receptor accessory protein. Proc Natl Acad Sci U S A. 1997;94:12829-32 pubmed
    ..An early IL-1 signaling event is the recruitment of the Ser/Thr kinase IRAK to the type I IL-1 receptor (IL-1RI)...
  67. Li C, Huang S, Mo S, Zhang N, Zhou L, Mao Z, et al. Susceptibility of autoimmune diseases in three polymorphisms of infection-associated gene IRAK1. J Infect Dev Ctries. 2015;9:614-23 pubmed publisher
    ..Our data demonstrated that these three SNPs (rs3027898, rs1059702, rs1059703) in IRAK1 were associated with ADs risk. ..
  68. Sanmiguel J, Olaru F, Li J, Mohr E, Jensen L. Interleukin-1 regulates keratinocyte expression of T cell targeting chemokines through interleukin-1 receptor associated kinase-1 (IRAK1) dependent and independent pathways. Cell Signal. 2009;21:685-94 pubmed publisher
    ..In conclusion IL-1 regulates T cell targeting chemokine production in keratinocytes through IRAK1 dependent and independent pathways. These pathways may contribute to acute and chronic skin inflammation. ..
  69. Li C, Wang J, Redmond H. Bacterial lipoprotein-induced self-tolerance and cross-tolerance to LPS are associated with reduced IRAK-1 expression and MyD88-IRAK complex formation. J Leukoc Biol. 2006;79:867-75 pubmed
    ..BLP-tolerant cells, whereas no significant differences in TLR4, MyD88, interleukin-1 receptor-associated kinase 4 (IRAK-4), and TNF receptor-associated factor 6 expression were observed between nontolerant and BLP-tolerant cells, as ..
  70. Zhou H, Du M, Dixit V. Constitutive NF-kappaB activation by the t(11;18)(q21;q21) product in MALT lymphoma is linked to deregulated ubiquitin ligase activity. Cancer Cell. 2005;7:425-31 pubmed
    ..Thus, t(11;18)(q21;q21) deregulates MALT1/paracaspase ubiquitin ligase activity, causing constitutive NF-kappaB activation and promoting tumorigenesis. ..
  71. Kopp E, Medzhitov R, Carothers J, Xiao C, Douglas I, Janeway C, et al. ECSIT is an evolutionarily conserved intermediate in the Toll/IL-1 signal transduction pathway. Genes Dev. 1999;13:2059-71 pubmed
    ..These results indicate an important role for ECSIT in signaling to NF-kappaB and suggest that processing of MEKK-1 is required for its function in the Toll/IL-1 pathway. ..
  72. Feng N, Zhou Z, Li Y, Zhao L, Xue Z, Lu R, et al. Enterovirus 71-induced has-miR-21 contributes to evasion of host immune system by targeting MyD88 and IRAK1. Virus Res. 2017;237:27-36 pubmed publisher
    ..Furthermore, we demonstrated that miR-21 targets the myeloid differentiation factor 88(MyD88) and interleukin-1 receptor-associated kinase 1(IRAK1), which are involved in EV71-induced type I IFN production. ..
  73. Deng Y, Yan Y, Tan K, Liu J, Chow V, Tao Z, et al. MicroRNA-146a induction during influenza H3N2 virus infection targets and regulates TRAF6 levels in human nasal epithelial cells (hNECs). Exp Cell Res. 2017;352:184-192 pubmed publisher
    ..hNEC model, we demonstrated that H3N2-induced miR-146a specifically targets and regulates TRAF6 expression; but not IRAK expression in the nasal epithelium...
  74. Keating S, Maloney G, Moran E, Bowie A. IRAK-2 participates in multiple toll-like receptor signaling pathways to NFkappaB via activation of TRAF6 ubiquitination. J Biol Chem. 2007;282:33435-43 pubmed
    ..signaling is known to involve interleukin-1 receptor-associated kinases (IRAKs), however the particular role of IRAK-2 has remained unclear...
  75. Park J, Son Y, Kim M, Cho J. Syk and IRAK1 Contribute to Immunopharmacological Activities of Anthraquinone-2-carboxlic Acid. Molecules. 2016;21: pubmed publisher
    ..Therefore, our data strongly suggest that AQCA-mediated suppression of inflammatory responses could be managed by a direct interference of signaling cascades including IRAK and Syk, linked to the activation of NF-κB and AP-1.
  76. Sturner K, Verse N, Yousef S, Martin R, Sospedra M. Boswellic acids reduce Th17 differentiation via blockade of IL-1?-mediated IRAK1 signaling. Eur J Immunol. 2014;44:1200-12 pubmed publisher
    ..The effects of AKBA on Th17 differentiation and IL-17A release make the compound a good candidate for potential treatment of Th17-driven diseases. ..