Gene interactions and pathways from curated databases and text-mining
Immunity 1997, PMID: 9430229

MyD88: an adapter that recruits IRAK to the IL-1 receptor complex.

Wesche, H; Henzel, W J; Shillinglaw, W; Li, S; Cao, Z

IL-1 is a proinflammatory cytokine that signals through a receptor complex of two different transmembrane chains to generate multiple cellular responses, including activation of the transcription factor NF-kappaB. Here we show that MyD88, a previously described protein of unknown function, is recruited to the IL-1 receptor complex following IL-1 stimulation. MyD88 binds to both IRAK (IL-1 receptor-associated kinase) and the heterocomplex (the signaling complex) of the two receptor chains and thereby mediates the association of IRAK with the receptor. Ectopic expression of MyD88 or its death domain-containing N-terminus activates NF-kappaB. The C-terminus of MyD88 interacts with the IL-1 receptor and blocks NF-kappaB activation induced by IL-1, but not by TNF. Thus, MyD88 plays the same role in IL-1 signaling as TRADD and Tube do in TNF and Toll pathways, respectively: it couples a serine/threonine protein kinase to the receptor complex.

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Text Mining Data

IRAK → MyD88: " MyD88 binds to both IRAK ( IL-1 receptor associated kinase ) and the heterocomplex ( the signaling complex ) of the two receptor chains and thereby mediates the association of IRAK with the receptor "

NF-kappaB → TNF: " The C-terminus of MyD88 interacts with the IL-1 receptor and blocks NF-kappaB activation induced by IL-1, but not by TNF "

NF-kappaB → IL-1: " The C-terminus of MyD88 interacts with the IL-1 receptor and blocks NF-kappaB activation induced by IL-1 , but not by TNF "

TNF — MyD88: " Thus, MyD88 plays the same role in IL-1 signaling as TRADD and Tube do in TNF and Toll pathways, respectively : it couples a serine/threonine protein kinase to the receptor complex "

IL-1 — MyD88: " Thus, MyD88 plays the same role in IL-1 signaling as TRADD and Tube do in TNF and Toll pathways, respectively : it couples a serine/threonine protein kinase to the receptor complex "

Manually curated Databases

  • IRef Innatedb Interaction: IL1R1 — IRAK1 (unknown, -)
  • NCI Pathway Database IL1-mediated signaling events: MYD88 (MYD88) → IL1 beta fragment/IL1R1/IL1RAP complex (IL1B-IL1R1-IL1RAP) (modification, collaborate)
    Evidence: mutant phenotype, physical interaction
  • NCI Pathway Database IL1-mediated signaling events: MYD88 (MYD88) → IL1 beta fragment/IL1R1/IL1RAP/MYD88 complex (IL1B-IL1R1-IL1RAP-MYD88) (modification, collaborate)
    Evidence: mutant phenotype, physical interaction
  • NCI Pathway Database IL1-mediated signaling events: IL1 beta fragment/IL1R1/IL1RAP complex (IL1B-IL1R1-IL1RAP) → IL1 beta fragment/IL1R1/IL1RAP/MYD88 complex (IL1B-IL1R1-IL1RAP-MYD88) (modification, collaborate)
    Evidence: mutant phenotype, physical interaction
  • NCI Pathway Database IL1-mediated signaling events: IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4 complex (IL1B-IL1R1-IL1RAP-MYD88-IRAK4) → IRAK/TOLLIP complex (IRAK1-TOLLIP) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction, other species
  • NCI Pathway Database IL1-mediated signaling events: IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4 complex (IL1B-IL1R1-IL1RAP-MYD88-IRAK4) → IRAKM (IRAK3) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction, other species
  • NCI Pathway Database IL1-mediated signaling events: IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4 complex (IL1B-IL1R1-IL1RAP-MYD88-IRAK4) → IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP complex (IL1B-IL1R1-IL1RAP-MYD88-IRAK4-IRAK1-TOLLIP) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction, other species
  • NCI Pathway Database IL1-mediated signaling events: IRAK/TOLLIP complex (IRAK1-TOLLIP) → IRAKM (IRAK3) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction, other species
  • NCI Pathway Database IL1-mediated signaling events: IRAK/TOLLIP complex (IRAK1-TOLLIP) → IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP complex (IL1B-IL1R1-IL1RAP-MYD88-IRAK4-IRAK1-TOLLIP) (modification, collaborate)
    Evidence: mutant phenotype, assay, physical interaction, other species
  • NCI Pathway Database IL1-mediated signaling events: IRAKM (IRAK3) → IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP complex (IL1B-IL1R1-IL1RAP-MYD88-IRAK4-IRAK1-TOLLIP) (modification, inhibits)
    Evidence: mutant phenotype, assay, physical interaction, other species
  • Reactome Reaction: MYD88 → TLR10 (reaction)
  • Reactome Reaction: MYD88 → TLR8 (reaction)
  • Reactome Reaction: MYD88 → TLR9 (reaction)
  • Reactome Reaction: IL1A → MYD88 (reaction)
  • Reactome Reaction: LY96 → MYD88 (reaction)
  • Reactome Reaction: MYD88 → IL1RAP (indirect_complex)
  • Reactome Reaction: IRAK4 → IRAK1 (indirect_complex)
  • Reactome Reaction: MYD88 → TLR7 (indirect_complex)
  • Reactome Reaction: MYD88 → TLR2 (reaction)
  • Reactome Reaction: MYD88 → TLR4 (indirect_complex)
  • Reactome Reaction: MYD88 → TLR4 (reaction)
  • Reactome Reaction: BTK → MYD88 (reaction)
  • Reactome Reaction: IL1R1 → MYD88 (indirect_complex)
  • Reactome Reaction: MYD88 → TLR9 (indirect_complex)
  • Reactome Reaction: CD14 → MYD88 (reaction)
  • Reactome Reaction: LY96 → MYD88 (indirect_complex)
  • Reactome Reaction: MYD88 → TLR2 (indirect_complex)
  • Reactome Reaction: CD14 → MYD88 (indirect_complex)
  • Reactome Reaction: TOLLIP → IRAK1 (indirect_complex)
  • Reactome Reaction: MYD88 → TLR8 (indirect_complex)
  • Reactome Reaction: MYD88 → TLR6 (indirect_complex)
  • Reactome Reaction: MYD88 → TLR6 (reaction)
  • Reactome Reaction: IL1A → IRAK1 (reaction)
  • Reactome Reaction: MYD88 → IL1RAP (reaction)
  • Reactome Reaction: IL1R1 → MYD88 (reaction)
  • Reactome Reaction: IL1A → MYD88 (indirect_complex)
  • Reactome Reaction: IL1R1 → IRAK1 (indirect_complex)
  • Reactome Reaction: IL1B → IRAK1 (reaction)
  • Reactome Reaction: MYD88 → TLR5 (indirect_complex)
  • Reactome Reaction: MYD88 → TIRAP (indirect_complex)
  • Reactome Reaction: IL1B → MYD88 (indirect_complex)
  • Reactome Reaction: IRAK1 → IL1RAP (reaction)
  • Reactome Reaction: CD36 → MYD88 (reaction)
  • Reactome Reaction: IL1R1 → IRAK1 (reaction)
  • Reactome Reaction: MYD88 → TLR10 (indirect_complex)
  • Reactome Reaction: IRAK1 → IL1RAP (indirect_complex)
  • Reactome Reaction: MYD88 → IRAK1 (reaction)
  • Reactome Reaction: MYD88 → TLR5 (reaction)
  • Reactome Reaction: IL1B → MYD88 (reaction)
  • Reactome Reaction: IL1A → IRAK1 (indirect_complex)
  • Reactome Reaction: IRAK4 → IRAK1 (reaction)
  • Reactome Reaction: MYD88 → IRAK1 (indirect_complex)
  • Reactome Reaction: CD36 → MYD88 (indirect_complex)
  • Reactome Reaction: IL1B → IRAK1 (indirect_complex)
  • Reactome Reaction: TOLLIP → IRAK1 (reaction)
  • Reactome Reaction: MYD88 → TLR7 (reaction)
  • Reactome Reaction: BTK → MYD88 (indirect_complex)
  • Reactome Reaction: MYD88 → TIRAP (reaction)
In total, 50 gene pairs are associated to this article in curated databases