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.
Lloyd, AT, Downing, T, Cormican, P, Bradley, D, O'Farrelly, C, Connell, SJ
Wesche, H, Li, S, Fontana, EJ, Strelow, A
© 2022 Reactome
