IRAK4

Summary

Gene Symbol: IRAK4
Description: interleukin 1 receptor associated kinase 4
Alias: IPD1, IRAK-4, NY-REN-64, REN64, interleukin-1 receptor-associated kinase 4, renal carcinoma antigen NY-REN-64
Species: human
Products:     IRAK4

Top Publications

  1. Tewfik M, Bosse Y, Lemire M, Hudson T, Vallée Smejda S, Al Shemari H, et al. Polymorphisms in interleukin-1 receptor-associated kinase 4 are associated with total serum IgE. Allergy. 2009;64:746-53 pubmed publisher
    ..A maximally informative set of SNPs in the TLR1, 2, 3, 4, 6, 9, 10, CD14, MD2, MyD88, IRAK4, and TRAF6 genes were selected and genotyped...
  2. Motshwene P, Moncrieffe M, Grossmann J, Kao C, Ayaluru M, Sandercock A, et al. An oligomeric signaling platform formed by the Toll-like receptor signal transducers MyD88 and IRAK-4. J Biol Chem. 2009;284:25404-11 pubmed publisher
    ..Taken together, these findings indicate that TLR activation causes the formation of a highly oligomeric signaling platform analogous to the death-inducing signaling complex of the Fas receptor pathway. ..
  3. Suzuki N, Suzuki S, Duncan G, Millar D, Wada T, Mirtsos C, et al. Severe impairment of interleukin-1 and Toll-like receptor signalling in mice lacking IRAK-4. Nature. 2002;416:750-6 pubmed
    ..In addition, animals lacking IRAK-4 are severely impaired in their responses to viral and bacterial challenges. Our results indicate that IRAK-4 has an essential role in innate immunity. ..
  4. 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
    ..Thus, MyD88s acts as a negative regulator of IL-1R/TLR/MyD88-triggered signals, leading to a transcriptionally controlled negative regulation of innate immune responses. ..
  5. 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
  6. Medvedev A, Thomas K, Awomoyi A, Kuhns D, Gallin J, Li X, et al. Cutting edge: expression of IL-1 receptor-associated kinase-4 (IRAK-4) proteins with mutations identified in a patient with recurrent bacterial infections alters normal IRAK-4 interaction with components of the IL-1 receptor complex. J Immunol. 2005;174:6587-91 pubmed
    ..Therefore, mimetics of these truncated IRAK-4 proteins may represent a novel approach to mitigating hyperinflammatory states. ..
  7. 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
    ..Pellino can be activated by phosphorylation in vitro, catalyzed by IL-1 receptor-associated kinase 1 (IRAK1) or IRAK4. Here, we show that phosphorylation enhances the E3 ligase activity of Pellino 1 similarly with any of several E2-..
  8. 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
    ..to which M1-pUb linkages are added subsequently, and myeloid differentiation primary response gene 88 (MyD88) and IRAK4 are also modified by both K63-pUb and M1-pUb chains...
  9. Suzuki N, Suzuki S, Yeh W. IRAK-4 as the central TIR signaling mediator in innate immunity. Trends Immunol. 2002;23:503-6 pubmed
    ..Understanding the role of IRAK-4 in innate immunity will enable us to design novel strategies for therapeutic intervention in human infectious disease. ..

More Information

Publications108 found, 100 shown here

  1. Rao N, Nguyen S, Ngo K, Fung Leung W. 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. Mol Cell Biol. 2005;25:6521-32 pubmed
    ..Unlike IRAK1, IRAK1c lacks kinase activity and cannot be phosphorylated by IRAK4. However, IRAK1c retains the ability to strongly interact with IRAK2, MyD88, Tollip, and TRAF6...
  2. Suzuki N, Saito T. IRAK-4--a shared NF-kappaB activator in innate and acquired immunity. Trends Immunol. 2006;27:566-72 pubmed
    ..Here, we discuss the impact of these evolutionarily conserved molecules on innate and acquired immunity, and their potential as drug targets for the simultaneous modulation of both immunities. ..
  3. Brikos C, Wait R, Begum S, O Neill L, Saklatvala J. Mass spectrometric analysis of the endogenous type I interleukin-1 (IL-1) receptor signaling complex formed after IL-1 binding identifies IL-1RAcP, MyD88, and IRAK-4 as the stable components. Mol Cell Proteomics. 2007;6:1551-9 pubmed
    ..The only component of the IL-1RI signaling complex that dissociated is IRAK-1. Our study is therefore the first detailed description of the endogenous IL-1RI complex. ..
  4. Lin S, Lo Y, Wu H. Helical assembly in the MyD88-IRAK4-IRAK2 complex in TLR/IL-1R signalling. Nature. 2010;465:885-90 pubmed publisher
    MyD88, IRAK4 and IRAK2 are critical signalling mediators of the TLR/IL1-R superfamily...
  5. 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
    ..As overexpression of Tollip results in impaired NF-kappaB activation, we conclude that Tollip is an important constituent of the IL-1R signalling pathway. ..
  6. Picard C, Puel A, Bonnet M, Ku C, Bustamante J, Yang K, et al. Pyogenic bacterial infections in humans with IRAK-4 deficiency. Science. 2003;299:2076-9 pubmed
    ..These findings suggest that, in humans, the TIR-IRAK signaling pathway is crucial for protective immunity against specific bacteria but is redundant against most other microorganisms. ..
  7. Medvedev A, Lentschat A, Kuhns D, Blanco J, Salkowski C, Zhang S, et al. Distinct mutations in IRAK-4 confer hyporesponsiveness to lipopolysaccharide and interleukin-1 in a patient with recurrent bacterial infections. J Exp Med. 2003;198:521-31 pubmed
    ..Thus, IRAK-4 is pivotal in the development of a normal inflammatory response initiated by bacterial or nonbacterial insults. ..
  8. 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
    ..The fact that IRAK4, another IRAK family member necessary for the IL-1 pathway, is able to phosphorylate IRAK in vitro suggests that ..
  9. Chapel H, Puel A, von Bernuth H, Picard C, Casanova J. Shigella sonnei meningitis due to interleukin-1 receptor-associated kinase-4 deficiency: first association with a primary immune deficiency. Clin Infect Dis. 2005;40:1227-31 pubmed
    ..sonnei infection in the intestinal mucosa. IRAK-4 deficiency and related disorders should be considered in patients with systemic shigellosis. ..
  10. Yang K, Puel A, Zhang S, Eidenschenk C, Ku C, Casrouge A, et al. Human TLR-7-, -8-, and -9-mediated induction of IFN-alpha/beta and -lambda Is IRAK-4 dependent and redundant for protective immunity to viruses. Immunity. 2005;23:465-78 pubmed
    ..The TLR-7-, TLR-8-, and TLR-9-dependent induction of IFN-alpha/beta and -lambda is strictly IRAK-4 dependent and paradoxically redundant for protective immunity to most viruses in humans. ..
  11. Ku C, von Bernuth H, Picard C, Zhang S, Chang H, Yang K, et al. Selective predisposition to bacterial infections in IRAK-4-deficient children: IRAK-4-dependent TLRs are otherwise redundant in protective immunity. J Exp Med. 2007;204:2407-22 pubmed
    ..Conversely, IRAK-4-dependent human TLRs appear to play a redundant role in protective immunity to most infections, at most limited to childhood immunity to some pyogenic bacteria. ..
  12. Kawagoe T, Sato S, Matsushita K, Kato H, Matsui K, Kumagai Y, et al. Sequential control of Toll-like receptor-dependent responses by IRAK1 and IRAK2. Nat Immunol. 2008;9:684-91 pubmed publisher
    ..IRAK2 was activated 'downstream' of IRAK4, like IRAK1, and TLR-induced cytokine production was abrogated in the absence of both IRAK1 and IRAK2...
  13. Zhang Y, Guo H, Cheng B, Su T, Fu X, Li T, et al. Dingchuan tang essential oil inhibits the production of inflammatory mediators via suppressing the IRAK/NF-κB, IRAK/AP-1, and TBK1/IRF3 pathways in lipopolysaccharide-stimulated RAW264.7 cells. Drug Des Devel Ther. 2018;12:2731-2748 pubmed publisher
    ..Moreover, degradation of interleukin-1 receptor-associated kinase 1 (IRAK1) and IRAK4 induced by LPS was inhibited by DCEO treatment...
  14. 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
    ..This is the first report that demonstrates that virulent mycobacteria manipulate the TLR2/4-MyD88-IRAK-4-p38-NF-?B-Camp-IL-1? pathway to survive inside bone marrow stem cells. ..
  15. González Rascón A, Mata Haro V. MicroRNAs: Regulators of TLR2-Mediated Probiotic Immune Responses. Microrna. 2015;4:168-74 pubmed
    ..and effective; proteins as TNF receptor-associated factor 6 (TRAF6), Interleukin-1 receptor-associated kinase 4 (IRAK4) and Interleukin-1 receptor-associated kinase 3 (IRAK3 or IRAKM) participate in an important way in the nuclear ..
  16. Xu K, Zhang Z, Xu Z, Tang Z, Liu L, Lu Z, et al. A novel invertebrate toll-like receptor is involved in TLR mediated signal pathway of thick shell mussel Mytilus coruscus. Dev Comp Immunol. 2019;97:11-19 pubmed publisher
    ..was obviously repressed by dsRNA-mediated RNA interference, and downstream TLR pathway factors, such as MyD88a, IRAK4, and TRAF6 were significantly repressed in McTLRj-silenced mussels upon LPS challenge...
  17. Wang P, Zhang Z, Xu Z, Guo B, Liao Z, Qi P. A novel invertebrate toll-like receptor with broad recognition spectrum from thick shell mussel Mytilus coruscus. Fish Shellfish Immunol. 2019;89:132-140 pubmed publisher
    ..of TLR signaling pathway myeloid differentiation factor 88a (MyD88a), interleukin-1 receptor-associated kinase-4 (IRAK4) and tumor necrosis factor receptor-associated factor 6 (TRAF6) were significantly repressed in McTLRw silenced ..
  18. Zhou B, Li Q, Wang J, Chen P, Jiang S. Ellagic acid attenuates streptozocin induced diabetic nephropathy via the regulation of oxidative stress and inflammatory signaling. Food Chem Toxicol. 2019;123:16-27 pubmed publisher
    ..serum albumin (Alb), serum TNF-α, renal function, anti-oxidative enzymes, and protein expression of TLR4, IRAK4, TRAF6, IKKβ, NF-κb P65, HMGB1 in renal tissue were determined...
  19. Liu P, Shah R, Li Y, Arora A, Ung P, Raman R, et al. An IRAK1-PIN1 signalling axis drives intrinsic tumour resistance to radiation therapy. Nat Cell Biol. 2019;21:203-213 pubmed publisher
    ..IRAK1 drives R-RT in a pathway involving IRAK4 and TRAF6 but not the IL-1R/TLR-IRAK adaptor MyD88...
  20. Maglione P, Simchoni N, Cunningham Rundles C. Toll-like receptor signaling in primary immune deficiencies. Ann N Y Acad Sci. 2015;1356:1-21 pubmed publisher
    ..Enhanced TLR responses, meanwhile, are seen for TLRs 5 and 9 in CGD, TLRs 4, 7/8, and 9 in XLA, TLRs 2 and 4 in hyper IgE syndrome, and for most TLRs in adenosine deaminase deficiency. ..
  21. Chasset F, Arnaud L. Targeting interferons and their pathways in systemic lupus erythematosus. Autoimmun Rev. 2018;17:44-52 pubmed publisher
    ..88 (MYD88), spleen tyrosine kinase (Syk), Janus-kinases (JAKs), interleukin-1 receptor-associated kinase 4 (IRAK4), or the Tyrosine Kinase 2 (TYK2) are also investigated actively in SLE, at more preliminary clinical development ..
  22. Yun L, Wu T, Li Q, Zhang M. Dietary supplementation with purified wheat germ glycoprotein improve immunostimulatory activity in cyclophosphamide induced Balb/c mice. Int J Biol Macromol. 2018;118:1267-1275 pubmed publisher
    ..inflammatory cytokines (IL-β, IL-6, IL-12, TNF-α mRNA), receptor protein (TLR2, TLR4) and protein kinase (IRAK4, TRAF6, TAK1, p38-MAPK, pho-p38-MAPK, NF-κB p65, and nucleu-NF-κB p65) production...
  23. 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. ..
  24. Biswas S, Xin L, Panigrahi S, Zimman A, Wang H, Yakubenko V, et al. Novel phosphatidylethanolamine derivatives accumulate in circulation in hyperlipidemic ApoE-/- mice and activate platelets via TLR2. Blood. 2016;127:2618-29 pubmed publisher
    ..assembly of TLR2/TLR1 receptor complex, induction of downstream signaling via MyD88/TIRAP, phosphorylation of IRAK4, and subsequent activation of tumor necrosis factor receptor-associated factor 6...
  25. Xu H, Yang M, Qiu W, Pan C, Wu M. The impact of endocrine-disrupting chemicals on oxidative stress and innate immune response in zebrafish embryos. Environ Toxicol Chem. 2013;32:1793-9 pubmed publisher
    ..Expressions of TLR3, TRIF, MyD88, SARM, IRAK4, and TRAF6 were altered on exposure to EDCs...
  26. Echavarria R, Mayaki D, Neel J, Harel S, Sanchez V, Hussain S. Angiopoietin-1 inhibits toll-like receptor 4 signalling in cultured endothelial cells: role of miR-146b-5p. Cardiovasc Res. 2015;106:465-77 pubmed publisher
    ..Prolonged Ang-1 exposure significantly decreases IRAK1 and TRAF6 protein levels but has no effect on TLR4, MYD88, IRAK4, or TAK1 expressions...
  27. Hunter Z, Yang G, Xu L, Liu X, Castillo J, Treon S. Genomics, Signaling, and Treatment of Waldenström Macroglobulinemia. J Clin Oncol. 2017;35:994-1001 pubmed publisher
    ..Mutated MYD88 triggers BTK, IRAK1/IRAK4, and HCK growth and survival signaling, whereas CXCR4 mutations promote AKT and extracellular regulated kinase-1/2 ..
  28. Pinheiro da Silva F, Gallo R, Nizet V. Differing effects of exogenous or endogenous cathelicidin on macrophage toll-like receptor signaling. Immunol Cell Biol. 2009;87:496-500 pubmed publisher
    ..These studies indicate the immunomodulatory effects of cathelicidin on macrophage TLR response may vary both on the exogenous vs endogenous origin of peptide and the prior activation state of the cell. ..
  29. Lemos D, McMurdo M, Karaca G, Wilflingseder J, Leaf I, Gupta N, et al. Interleukin-1β Activates a MYC-Dependent Metabolic Switch in Kidney Stromal Cells Necessary for Progressive Tubulointerstitial Fibrosis. J Am Soc Nephrol. 2018;29:1690-1705 pubmed publisher
    ..Inhibition of the IL-1R signal transducer kinase IRAK4 in vivo or inhibition of MYC in vivo as well as in human kidney organoids in vitro abrogated ..
  30. Wei J, Zhou T, Hu Z, Li Y, Yuan H, Zhao K, et al. Effects of triclocarban on oxidative stress and innate immune response in zebrafish embryos. Chemosphere. 2018;210:93-101 pubmed publisher
    ..Expressions of nf-?b, trif, myd88, irak4, and traf6 were altered on exposure to TCC...
  31. Hu X, Fu X, Li N, Dong X, Zhao L, Lan J, et al. Transcriptomic analysis of Mandarin fish brain cells infected with infectious spleen and kidney necrosis virus with an emphasis on retinoic acid-inducible gene 1-like receptors and apoptosis pathways. Fish Shellfish Immunol. 2015;45:619-29 pubmed publisher
    ..expression of the IKKB-α and IKKB-β and lessened expression of interleukin-1 receptor-associated kinase 4 (IRAK4)...
  32. Ryu H, Lee H, Kim J, Kim Y, Pyo M, Yun J, et al. Saucerneol D inhibits dendritic cell activation by inducing heme oxygenase-1, but not by directly inhibiting toll-like receptor 4 signaling. J Ethnopharmacol. 2015;166:92-101 pubmed publisher
    ..activation of NF-κB and MAPK signaling in DCs, but did not directly inhibit kinase activities of IRAK1, IRAK4, TAK1, or IKKβ in enzymatic assays...
  33. Bruni D, Chazal M, Sinigaglia L, Chauveau L, Schwartz O, Desprès P, et al. Viral entry route determines how human plasmacytoid dendritic cells produce type I interferons. Sci Signal. 2015;8:ra25 pubmed publisher
    ..the RLR pathway was dampened by the activities of interleukin-1 receptor-associated kinases 1 and 4 (IRAK1 and IRAK4), which are downstream effectors of the TLR7 pathway, suggesting that both kinases play opposing roles downstream ..
  34. 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
    ..b>IRAK4 and IRAK1 function as active kinases and as scaffolds for protein-protein interactions...
  35. Di Stefano A, Ricciardolo F, Caramori G, Adcock I, Chung K, Barnes P, et al. Bronchial inflammation and bacterial load in stable COPD is associated with TLR4 overexpression. Eur Respir J. 2017;49: pubmed publisher
    ..domain-containing adaptor protein (TIRAP), and the interleukin-1 receptor-associated kinases phospho-IRAK1 and IRAK4 were measured in the bronchial mucosa of subjects with stable COPD of different severity (n=34), control smokers (..
  36. Frans G, Meert W, van der Werff ten Bosch J, Meyts I, Bossuyt X, Vermeesch J, et al. Conventional and Single-Molecule Targeted Sequencing Method for Specific Variant Detection in IKBKG while Bypassing the IKBKGP1 Pseudogene. J Mol Diagn. 2018;20:195-202 pubmed publisher
    ..We therefore developed a long-range PCR method to efficiently target IKBKG, as well as two associated genes (IRAK4 and MYD88), while bypassing the IKBKGP1 pseudogene...
  37. Liu G, Tsuruta Y, Gao Z, Park Y, Abraham E. Variant IL-1 receptor-associated kinase-1 mediates increased NF-kappa B activity. J Immunol. 2007;179:4125-34 pubmed
  38. He L, Tong X, Zeng J, Tu Y, Wu S, Li M, et al. Paeonol Suppresses Neuroinflammatory Responses in LPS-Activated Microglia Cells. Inflammation. 2016;39:1904-1917 pubmed
    ..in immune signaling pathways and found that PAE treatment significantly decreased the expression of TLR4, MyD88, IRAK4, TNFR-associated factor 6 (TRAF6), p-IkB-?, and NF-kB p65, as well as the mitogen-activated protein kinase (MAPK) ..
  39. Sun K, Xu D, Xie C, Plummer S, Tang J, Yang X, et al. Lactobacillus paracasei modulates LPS-induced inflammatory cytokine release by monocyte-macrophages via the up-regulation of negative regulators of NF-kappaB signaling in a TLR2-dependent manner. Cytokine. 2017;92:1-11 pubmed publisher
    ..Pretreatment with an IRAK4 inhibitor suppressed the L...
  40. Kim S, Park J, Lee J, Yang W, Park G, Kim H, et al. The dietary flavonoid Kaempferol mediates anti-inflammatory responses via the Src, Syk, IRAK1, and IRAK4 molecular targets. Mediators Inflamm. 2015;2015:904142 pubmed publisher
    ..Interestingly, it was found that Src, Syk, IRAK1, and IRAK4 responsible for NF-κB and AP-1 activation were identified as the direct molecular targets of KF by kinase ..
  41. Patra M, Choi S. Recent Progress in the Molecular Recognition and Therapeutic Importance of Interleukin-1 Receptor-Associated Kinase 4. Molecules. 2016;21: pubmed
    ..Interleukin-1 receptor-associated kinase 4 (IRAK4) is a key mediator in TLR (except for TLR3) and interleukin-1 receptor signaling pathways...
  42. Scott J, Degorce S, Anjum R, Culshaw J, Davies R, Davies N, et al. Discovery and Optimisation of Pyrrolopyrimidine Inhibitors of Interleukin-1 Receptor Associated Kinase 4 (IRAK4) for the Treatment of Mutant MYD88L265P Diffuse Large B-Cell Lymphoma. J Med Chem. 2017;: pubmed publisher
    ..report the optimization of a series of pyrrolopyrimidine inhibitors of interleukin-1 receptor associated kinase 4 (IRAK4) using X-ray crystal structures and structure based design to identify and optimize our scaffold...
  43. Srivastav S, Saha A, Barua J, Ukil A, Das P. IRAK-M regulates the inhibition of TLR-mediated macrophage immune response during late in vitro Leishmania donovani infection. Eur J Immunol. 2015;45:2787-97 pubmed publisher
    ..Our data reveal a sharp decline in IRAK1 and IRAK4 phosphorylation at 24 h postinfection along with markedly reduced association of IRAK1-TNF receptor associated ..
  44. Dudhgaonkar S, Ranade S, Nagar J, Subramani S, Prasad D, Karunanithi P, et al. Selective IRAK4 Inhibition Attenuates Disease in Murine Lupus Models and Demonstrates Steroid Sparing Activity. J Immunol. 2017;198:1308-1319 pubmed publisher
    ..We have identified BMS-986126, a potent, highly selective inhibitor of IRAK4 kinase activity that demonstrates equipotent activity against multiple MyD88-dependent responses both in vitro and ..
  45. Sun J, Li N, Oh K, Dutta B, Vayttaden S, Lin B, et al. Comprehensive RNAi-based screening of human and mouse TLR pathways identifies species-specific preferences in signaling protein use. Sci Signal. 2016;9:ra3 pubmed publisher
    ..Whereas TLR signaling in mouse macrophages depended primarily on IRAK4 and IRAK2, with little or no role for IRAK1, TLR signaling and proinflammatory cytokine production in human ..
  46. Kang L, Zhang D, Ma C, Zhang J, Jia K, Liu J, et al. Cinnamaldehyde and allopurinol reduce fructose-induced cardiac inflammation and fibrosis by attenuating CD36-mediated TLR4/6-IRAK4/1 signaling to suppress NLRP3 inflammasome activation. Sci Rep. 2016;6:27460 pubmed publisher
    ..Scavenger receptor CD36, Toll-like receptor 4 (TLR4), TLR6, IL-1R-associated kinase 4/1 (IRAK4/1), nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome, interleukin-1β, transforming ..
  47. Tian F, Yuan C, Hu L, Shan S. MicroRNA-93 inhibits inflammatory responses and cell apoptosis after cerebral ischemia reperfusion by targeting interleukin-1 receptor-associated kinase 4. Exp Ther Med. 2017;14:2903-2910 pubmed publisher
    ..The present study aimed to investigate changes in the expression of interleukin (IL)-1 receptor-associated kinase 4 (IRAK4) and microRNA (miRNA or miR)-93 in mice with cerebral ischemia reperfusion (CIR) injury, as well as the ..
  48. Cushing L, Winkler A, Jelinsky S, Lee K, Korver W, Hawtin R, et al. IRAK4 kinase activity controls Toll-like receptor-induced inflammation through the transcription factor IRF5 in primary human monocytes. J Biol Chem. 2017;292:18689-18698 pubmed publisher
    Interleukin-1 receptor-associated kinase 4 (IRAK4) plays a critical role in innate immune signaling by Toll-like receptors (TLRs), and loss of IRAK4 activity in mice and humans increases susceptibility to bacterial infections and causes ..
  49. Zhou J, Wu R, High A, Slaughter C, Finkelstein D, Rehg J, et al. A20-binding inhibitor of NF-?B (ABIN1) controls Toll-like receptor-mediated CCAAT/enhancer-binding protein ? activation and protects from inflammatory disease. Proc Natl Acad Sci U S A. 2011;108:E998-1006 pubmed publisher
    ..Together, our data reveal ABIN1 as an essential anti-inflammatory component of TLR-signaling pathways that controls C/EBP? activity. ..
  50. Ren Y, Ding D, Pan B, Bu W. The TLR13-MyD88-NF-?B signalling pathway of Cyclina sinensis plays vital roles in innate immune responses. Fish Shellfish Immunol. 2017;70:720-730 pubmed publisher
    ..In the present research, the cDNA and protein characterization of the TLR signalling pathway genes including IRAK4, TRAK6 and IKK? (named CsIRAK4, CsTRAF6 and CsIKK?, respectively) with the typical motifs from Cyclina sinensis ..
  51. Siu G, Strauss E, Lai E, Hood L. Analysis of a human V beta gene subfamily. J Exp Med. 1986;164:1600-14 pubmed
    ..Analyses of the genomic clones show that the spacing distance between germline V beta gene segments ranges from 3 kb to greater than 30 kb, and the entire V beta 8 subfamily appears to be linked by a total of no more than 110 kb of DNA. ..
  52. Yang Z, Huang B, Zhang Z, Kang Y, Fu M, Liao W. Effects of IL-1 receptor-associated kinase-4 gene silencing on human osteoblast-like cells. Connect Tissue Res. 2012;53:498-507 pubmed publisher
    ..The results of this study may help improve the understanding of the relationship between IRAK-4 and osteoblast-like cells and the interactions between various cytokines in the periprosthetic inflammatory environment. ..
  53. Seganish W, McElroy W, Herr R, Brumfield S, Greenlee W, Harding J, et al. Initial optimization and series evolution of diaminopyrimidine inhibitors of interleukin-1 receptor associated kinase 4. Bioorg Med Chem Lett. 2015;25:3203-7 pubmed publisher
    b>IRAK4 plays a key role in TLR/IL-1 signaling. Previous efforts identified a series of aminopyrimidine IRAK4 inhibitors that possess good potency, but modest kinase selectivity...
  54. Nanda S, López Pelaéz M, Arthur J, Marchesi F, Cohen P. Suppression of IRAK1 or IRAK4 Catalytic Activity, but Not Type 1 IFN Signaling, Prevents Lupus Nephritis in Mice Expressing a Ubiquitin Binding-Defective Mutant of ABIN1. J Immunol. 2016;197:4266-4273 pubmed
    ..In contrast, crossing ABIN1[D485N] mice to knock-in mice expressing catalytically inactive mutants of IRAK1 or IRAK4 prevented splenomegaly, autoimmunity, and liver and kidney inflammation...
  55. Gay N, Gangloff M, O Neill L. What the Myddosome structure tells us about the initiation of innate immunity. Trends Immunol. 2011;32:104-9 pubmed publisher
  56. Jeon J, Lee J, Park K, Byun H, Lee H, Lee Y, et al. Brazilin selectively disrupts proximal IL-1 receptor signaling complex formation by targeting an IKK-upstream signaling components. Biochem Pharmacol. 2014;89:515-25 pubmed publisher
    ..Taken together, the results suggest that the anti-IKK activity of brazilin is induced by targeting IKK upstream signaling components and subsequently disrupting proximal IL-1 receptor signaling complex formation. ..
  57. Ng G, Menheniott T, Every A, Stent A, Judd L, Chionh Y, et al. The MUC1 mucin protects against Helicobacter pylori pathogenesis in mice by regulation of the NLRP3 inflammasome. Gut. 2016;65:1087-99 pubmed publisher
    ..via an nuclear factor (NF)-κB-dependent pathway and reduced NF-κB pathway activation via inhibition of IRAK4 phosphorylation...
  58. 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
    ..meningitis as the initial manifestation of IRAK-4 deficiency caused by previously undescribed mutations in IRAK4. The letter also highlights the importance of invasive pneumococcal infection as a critical 'red flag' warning of ..
  59. Ji J, Xu J, Li F, Li X, Gong W, Song Y, et al. A benzenediamine derivate FC-99 attenuates lupus nephritis in MRL/lpr mice via inhibiting myeloid dendritic cell-secreted BAFF. Acta Biochim Biophys Sin (Shanghai). 2016;48:411-9 pubmed publisher
    ..FC-99 possesses anti-inflammation activity and directly interacts with interleukin-1 receptor-associated kinase 4 (IRAK4), which was a pivotal molecule in TLR4 signaling...
  60. Rininsland F, Stankewicz C, Weatherford W, McBranch D. High-throughput kinase assays with protein substrates using fluorescent polymer superquenching. BMC Biotechnol. 2005;5:16 pubmed
    ..proteins was detected by Protein Kinase Calpha (PKCalpha) and by the Interleukin -1 Receptor-associated Kinase 4 (IRAK4). Enzyme inhibition yielded IC50 values that were comparable to those obtained using peptide substrates...
  61. 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
    ..Phosphorylation of IRAK-1 by IRAK-4 in response to TLR activation may then release IRAK-1 from the inhibitory constraint exerted by its C-terminal domain. ..
  62. Maglione P, Simchoni N, Black S, Radigan L, Overbey J, Bagiella E, et al. IRAK-4 and MyD88 deficiencies impair IgM responses against T-independent bacterial antigens. Blood. 2014;124:3561-71 pubmed publisher
    ..Thus, by bolstering the IgM(+)IgD(+)CD27(+) B-cell subset, IRAK-4 and MyD88 promote optimal T-independent IgM antibody responses against bacteria in humans. ..
  63. Brown K, Falsafi R, Kum W, Hamill P, Gardy J, Davidson D, et al. Robust TLR4-induced gene expression patterns are not an accurate indicator of human immunity. J Transl Med. 2010;8:6 pubmed publisher
    ..Many TLRs utilize a common signalling pathway that relies on activation of the kinase IRAK4 and the transcription factor NFkappaB for the rapid expression of immunity genes...
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    ..Recruitment of TRAF6 to the receptor-associated IRAK1-IRAK4-MyD88 adaptor protein complex induces lysine 63 (K63) autopolyubiquitination of TRAF6, which leads to further ..
  65. Leleux J, Pradhan P, Roy K. Biophysical Attributes of CpG Presentation Control TLR9 Signaling to Differentially Polarize Systemic Immune Responses. Cell Rep. 2017;18:700-710 pubmed publisher
    ..These physical patterns control DC programming by regulating the kinetics and magnitude of MyD88-IRAK4 signaling, NF-?B-driven responses, and STAT3 phosphorylation, which, in turn, controls differential T cell ..
  66. Eda H, Burnette B, Shimada H, Hope H, Monahan J. Interleukin-1?-induced interleukin-6 production in A549 cells is mediated by both phosphatidylinositol 3-kinase and interleukin-1 receptor-associated kinase-4. Cell Biol Int. 2011;35:355-8 pubmed publisher
    ..siRNA (small interfering RNA) of IRAK4 (IL-1 receptor-associated kinase 4) treatment decreased IRAK4 mRNA level by up to 90% in A549 cells...
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    Interleukin-1 receptor-associated kinase (IRAK) 4 mediates host defense against infections. As an active kinase, IRAK4 elicits full spectra of myeloid differentiation primary response protein (MyD) 88-dependent responses, while kinase-..
  68. 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
    ..Thus, IRAK-1 regulates its own availability as an adapter molecule by sequential autophosphorylation. ..
  69. Hoarau C, Gerard B, Lescanne E, Henry D, Francois S, Lacapere J, et al. TLR9 activation induces normal neutrophil responses in a child with IRAK-4 deficiency: involvement of the direct PI3K pathway. J Immunol. 2007;179:4754-65 pubmed
    ..Analysis of the IRAK4 gene showed compound heterozygosity with two mutations: a missense mutation in the death domain of the protein (..
  70. He B, Santamaria R, Xu W, Cols M, Chen K, Puga I, et al. The transmembrane activator TACI triggers immunoglobulin class switching by activating B cells through the adaptor MyD88. Nat Immunol. 2010;11:836-45 pubmed publisher
    ..CSR via the DNA-editing enzyme AID by activating NF-kappaB through a Toll-like receptor (TLR)-like MyD88-IRAK1-IRAK4-TRAF6-TAK1 pathway...
  71. Over B, Ziegler S, Foermer S, Weber A, Bode K, Heeg K, et al. IRAK4 turns IL-10+ phospho-FOXO+ monocytes into pro-inflammatory cells by suppression of protein kinase B. Eur J Immunol. 2013;43:1630-42 pubmed publisher
    b>IRAK4, a serine/threonine kinase is a central adaptor protein in TLR signaling. To better understand the clinical significance of IRAK4 deficiency we examined the impact of IRAK4 on bacterial recognition in human monocytes...
  72. Halderman A, Lane A. Genetic and Immune Dysregulation in Chronic Rhinosinusitis. Otolaryngol Clin North Am. 2017;50:13-28 pubmed publisher
    ..Current evidence for a genetic basis of CRS is reviewed, as it pertains to putative abnormalities in innate and adaptive immune function. The role of systemic immunodeficiencies in refractory CRS is discussed. ..
  73. Nakagawa S. [Identification of Biomarkers for Tubular Injury and Interstitial Fibrosis in Chronic Kidney Disease]. Yakugaku Zasshi. 2017;137:1355-1360 pubmed publisher
    ..of MyD88 in pericytes, or pharmacological inhibition of MyD88 signaling by an IL-1 receptor-associated kinase 4 (IRAK4) inhibitor, halted interstitial fibrosis after renal tubular injury...
  74. Cheng H, Addona T, Keshishian H, Dahlstrand E, Lu C, Dorsch M, et al. Regulation of IRAK-4 kinase activity via autophosphorylation within its activation loop. Biochem Biophys Res Commun. 2007;352:609-16 pubmed
    ..The present data indicate that the kinase activity of IRAK-4 is dependent on the autophosphorylations at T342, T345, and S346 in the activation loop. ..
  75. Butler M, Hanly J, Moynagh P. Kinase-active interleukin-1 receptor-associated kinases promote polyubiquitination and degradation of the Pellino family: direct evidence for PELLINO proteins being ubiquitin-protein isopeptide ligases. J Biol Chem. 2007;282:29729-37 pubmed
  76. Sun M, Yang P, Du L, Yang Y, Ye J. The role of interleukin-1 receptor-associated kinases in Vogt-Koyanagi-Harada disease. PLoS ONE. 2014;9:e93214 pubmed publisher
    To explore whether IRAK1 and IRAK4 are involved in the pathogenesis of Vogt-Koyanagi-Harada (VKH) disease. Thirty-nine VKH patients and thirty-two healthy controls were included in this study...
  77. Ulrichts P, Tavernier J. MAPPIT analysis of early Toll-like receptor signalling events. Immunol Lett. 2008;116:141-8 pubmed publisher
    ..We demonstrate pathway walking from TLR4 to IRAK-1 and identified Mal as a bridging adaptor, linking MyD88 to the activated TLR4. ..
  78. Smith H, Liu X, Dai L, Goh E, Chan A, Xi J, et al. The role of TBK1 and IKKε in the expression and activation of Pellino 1. Biochem J. 2011;434:537-48 pubmed publisher
    Mammalian Pellino isoforms are phosphorylated by IRAK (interleukin receptor associated kinase) 1/IRAK4 in vitro, converting them into active E3 ubiquitin ligases...
  79. Kumar D, Patil V, Ramachandran B, Nila M, Dharmalingam K, Somasundaram K. Temozolomide-modulated glioma proteome: role of interleukin-1 receptor-associated kinase-4 (IRAK4) in chemosensitivity. Proteomics. 2013;13:2113-24 pubmed publisher
    ..upregulated spots: aspartyl tRNA synthetase glutathione synthetase, interleukin-1 receptor-associated kinase-4 (IRAK4), and breast carcinoma amplified sequence-1 and one downregulated spot: optineurin...
  80. Chang H, Wang Y, Yin X, Liu X, Xuan H. Ethanol extract of propolis and its constituent caffeic acid phenethyl ester inhibit breast cancer cells proliferation in inflammatory microenvironment by inhibiting TLR4 signal pathway and inducing apoptosis and autophagy. BMC Complement Altern Med. 2017;17:471 pubmed publisher
    ..The levels of TLR4, MyD88, IRAK4, TRIF, caspase 3, PARP, LC3B and p62 were investigated through western blotting...
  81. Weller S, Bonnet M, Delagrèverie H, Israel L, Chrabieh M, Marodi L, et al. IgM+IgD+CD27+ B cells are markedly reduced in IRAK-4-, MyD88-, and TIRAP- but not UNC-93B-deficient patients. Blood. 2012;120:4992-5001 pubmed publisher
    ..Hence, we propose a role for TIRAP-dependent TLRs, possibly TLR10 in particular, in the development and/or maintenance of IgM(+)IgD(+)CD27(+) B cells in humans. ..
  82. Cameron B, Tse W, Lamb R, Li X, Lamb B, Landreth G. Loss of interleukin receptor-associated kinase 4 signaling suppresses amyloid pathology and alters microglial phenotype in a mouse model of Alzheimer's disease. J Neurosci. 2012;32:15112-23 pubmed publisher
    ..Therefore, we disrupted a common downstream TLR signaling element, IRAK4. We report that microglial IRAK4 is necessary in vitro for fA? to activate the canonical pro-inflammatory ..
  83. Ferrao R, Zhou H, Shan Y, Liu Q, Li Q, Shaw D, et al. IRAK4 dimerization and trans-autophosphorylation are induced by Myddosome assembly. Mol Cell. 2014;55:891-903 pubmed publisher
    ..In Toll-like receptor and interleukin-1 receptor signaling pathways, the kinase IRAK4 is recruited to the membrane-proximal adaptor MyD88 through death domain (DD) interactions, forming the oligomeric ..
  84. Zhang D, Li L, Jiang H, Knolhoff B, Lockhart A, Wang Gillam A, et al. Constitutive IRAK4 Activation Underlies Poor Prognosis and Chemoresistance in Pancreatic Ductal Adenocarcinoma. Clin Cancer Res. 2017;23:1748-1759 pubmed publisher
    ..b>Experimental Design: We examined the phosphorylation status of IRAK4 (p-IRAK4), the master regulator of TLR signaling, in PDAC cell lines, in surgical samples and commercial tissue ..
  85. Smith G, Altman M, Andresen B, Baker J, Brubaker J, Chen H, et al. Identification of quinazoline based inhibitors of IRAK4 for the treatment of inflammation. Bioorg Med Chem Lett. 2017;27:2721-2726 pubmed publisher
    Interleukin-1 receptor associated kinase 4 (IRAK4) has been implicated in IL-1R and TLR based signaling...
  86. Bhide R, Keon A, Weigelt C, Sack J, Schmidt R, Lin S, et al. Discovery and structure-based design of 4,6-diaminonicotinamides as potent and selective IRAK4 inhibitors. Bioorg Med Chem Lett. 2017;27:4908-4913 pubmed publisher
    The identification of small molecule inhibitors of IRAK4 for the treatment of autoimmune diseases has been an area of intense research. We discovered novel 4,6-diaminonicotinamides which potently inhibit IRAK4...
  87. Srivastava N, Shelly A, Kumar M, Pant A, Das B, Majumdar T, et al. Aeromonas hydrophila utilizes TLR4 topology for synchronous activation of MyD88 and TRIF to orchestrate anti-inflammatory responses in zebrafish. Cell Death Discov. 2017;3:17067 pubmed publisher
    ..i. Quantitative PCR studies suggest that TLR4 activates the downstream pathway of MyD88-IRAK4 axis at early stages followed by a shift to TRIF-TRAF6 axis at late stages of infection coupled with fold increase ..
  88. Loiarro M, Capolunghi F, Fantò N, Gallo G, Campo S, Arseni B, et al. Pivotal Advance: Inhibition of MyD88 dimerization and recruitment of IRAK1 and IRAK4 by a novel peptidomimetic compound. J Leukoc Biol. 2007;82:801-10 pubmed
    ..of downstream signaling molecules such as the serine/threonine kinases IL-1R-associated kinase 1 (IRAK1) and IRAK4. Herein, we have synthesized and tested the activity of a synthetic peptido-mimetic compound (ST2825) modeled ..
  89. Nahid M, Yao B, Dominguez Gutierrez P, Kesavalu L, Satoh M, Chan E. Regulation of TLR2-mediated tolerance and cross-tolerance through IRAK4 modulation by miR-132 and miR-212. J Immunol. 2013;190:1250-63 pubmed publisher
    ..Mechanistically, IRAK4 was identified and validated as a target of miR-132/-212 by luciferase reporter assay and seed-sequence ..
  90. Picard C, von Bernuth H, Ku C, Yang K, Puel A, Casanova J. Inherited human IRAK-4 deficiency: an update. Immunol Res. 2007;38:347-52 pubmed
    ..We briefly review inherited human IRAK-4 deficiency, a recently described primary immunodeficiency leading to recurrent, invasive, pyogenic bacteria infection, and invasive pneumococcal disease in particular. ..
  91. Isnardi I, Ng Y, Srdanovic I, Motaghedi R, Rudchenko S, von Bernuth H, et al. IRAK-4- and MyD88-dependent pathways are essential for the removal of developing autoreactive B cells in humans. Immunity. 2008;29:746-57 pubmed publisher
  92. Bouma G, Doffinger R, Patel S, Peskett E, Sinclair J, Barcenas Morales G, et al. Impaired neutrophil migration and phagocytosis in IRAK-4 deficiency. Br J Haematol. 2009;147:153-6 pubmed publisher