Interleukin-1 receptor-associated kinase 1 (IRAK1)

Interleukin-1 receptor-associated kinase 1 (IRAK1) is a serine/threonine protein kinase that plays a central role in innate immune signaling, particularly in the pathways mediated by Toll-like receptors (TLRs) and interleukin-1 receptors (IL-1Rs). It is rapidly recruited to the receptor-signaling complex upon activation of TLRs or IL-1R, primarily through interaction with the adaptor protein MyD88. Once recruited, IRAK4 phosphorylates IRAK1, which then undergoes autophosphorylation and becomes fully activated. Activated IRAK1 phosphorylates E3 ubiquitin ligases such as Pellino proteins to promote polyubiquitination and forms complexes with TRAF6 and TAK1-binding proteins, leading to activation of downstream kinases including MAPKs and IKKs. Ultimately, this results in nuclear translocation of NF-kappa B (NF‑κB) and AP‑1 transcription factors, driving expression of pro-inflammatory genes. Targeting/inhibiting IRAK family kinases—especially selective inhibition of IRAK‑I—is being explored for treating cancers as well as metabolic/inflammatory diseases due to their pivotal roles in disease pathogenesis.

Other names

IRAK-1

Inhibition of IRAK1 kinase activity