Reactome | IRAK4 recruitment to the activated TLR complexed with ligand, TIRAP and MyD88

IRAK4 recruitment to the activated TLR complexed with ligand, TIRAP and MyD88

Stable Identifier

R-GGA-434073

Type

Reaction [binding]

Species

Gallus gallus

Compartment

plasma membrane, cytosol

ReviewStatus

5/5

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IRAK4 recruitment to the activated TLR complexed with ligand, TIRAP and MyD88

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Mammalian IL-1 receptor-associated kinases IRAK-1, IRAK-2 and IRAK-4 form a multigene family. Those proteins are Ser/Thr protein kinases that are required for TLR mediated pathways leading to NFkB activation. Another IRAK family member IRAK-M has been identified as an inhibitor of TLR signaling.

Mammalian IRAK-4 is the homolog of Drosophila melanogaster Pelle. Like Pelle and unlike the other mammalian IRAKs, IRAK-4 is considered to be a central TIR signalling mediator in innate immunity. Mutagenesis analysis showed that any interference with IRAK-4's kinase activity virtually abolished downstream events. This is not the case with other members of the IRAK family.

Formation of MyD88:IRAKs multimer relies on homotypic interactions of death domains (DD). It triggers a cascade of phosphorylation reactions that leads to activation of NF-kB/AP-1 and transcription of multiple genes involved in the immune response.

The predicted chicken full-length IRAK-4 protein contains 414aa and is 58% identical to human IRAK-4. Chicken IRAK-4 contains a conserved N-terminal death domain and C-terminal protein kinase domain.

Literature References

PubMed ID	Title	Journal	Year
11923871	Severe impairment of interleukin-1 and Toll-like receptor signalling in mice lacking IRAK-4 Suzuki, N, Suzuki, S, Duncan, GS, Millar, DG, Wada, T, Mirtsos, C, Takada, H, Wakeham, A, Itie, A, Li, S, Penninger, JM, Wesche, H, Ohashi, PS, Mak, TW, Yeh, WC	Nature	2002
19539094	The avian Toll-Like receptor pathway--subtle differences amidst general conformity Cormican, P, Lloyd, AT, Downing, T, Connell, SJ, Bradley, D, O'Farrelly, C	Dev Comp Immunol	2009
11960013	IRAK-4: a novel member of the IRAK family with the properties of an Li, S, Strelow, A, Fontana, EJ, Wesche, H	Proc Natl Acad Sci U S A	2002