IRAK1 Protein, Human (Active, sf9, GST)

IRAK1, a serine/threonine-protein kinase, assumes a crucial role in initiating the innate immune response against foreign pathogens by participating in Toll-like receptor (TLR) and IL-1R signaling pathways. Upon TLR activation, IRAK1 is swiftly recruited by MYD88 to the receptor-signaling complex, leading to its phosphorylation by IRAK4, subsequent autophosphorylation, and activation of its kinase function. IRAK1 then phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2, and PELI3), promoting pellino-mediated polyubiquitination of IRAK1. The ubiquitin-binding domain of IKBKG/NEMO binds to polyubiquitinated IRAK1, facilitating the assembly of the IRAK1-MAP3K7/TAK1-TRAF6 complex and the NEMO-IKKA-IKKB complex. This cascade activates IKKs (CHUK/IKKA and IKBKB/IKKB), leading to NF-kappa-B nuclear translocation and activation. Additionally, IRAK1 phosphorylates TIRAP, promoting its ubiquitination and degradation. Furthermore, IRAK1 phosphorylates interferon regulatory factor 7 (IRF7), inducing its activation and translocation to the nucleus, thereby initiating the transcriptional activation of type I IFN genes, establishing an antiviral cellular state. When sumoylated, IRAK1 translocates to the nucleus and phosphorylates STAT3.