IRAK4 Protein, Human (Active, sf9, His-Strep)

The IRAK4 protein functions as a pivotal serine/threonine-protein kinase, playing a crucial role in initiating the innate immune response against foreign pathogens. It is actively involved in Toll-like receptor (TLR) and IL-1R signaling pathways, and upon TLR activation, it is rapidly recruited by MYD88 to form the Myddosome in conjunction with IRAK2. Initially, IRAK1 is phosphorylated, stimulating its kinase activity and inducing intensive autophosphorylation. Additionally, IRAK4 phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2, and PELI3), facilitating pellino-mediated polyubiquitination of IRAK1. Consequently, the polyubiquitinated IRAK1 binds with the ubiquitin-binding domain of IKBKG/NEMO, assembling the IRAK1-MAP3K7/TAK1-TRAF6 complex and the NEMO-IKKA-IKKB complex. This, in turn, activates IKKs (CHUK/IKKA and IKBKB/IKKB), leading to nuclear translocation and activation of NF-kappa-B. Alternatively, TIRAP is phosphorylated by IRAK4, promoting its ubiquitination and subsequent degradation. Moreover, IRAK4 phosphorylates NCF1, which regulates NADPH oxidase activation following LPS stimulation, suggesting a similar mechanism during microbial infections.