IRAK4
IRAK4 (interleukin 1 receptor associated kinase 4, also known as NY-REN-64) is a serine/threonine-protein kinase that initiates innate immune responses against foreign pathogens. It acts downstream of Toll-like receptors and the IL-1 receptor to drive NF-kappa-B activation. Browse Assay Genie's current range of IRAK4 research reagents below, or read on for the biology behind the target.
IRAK4 is a serine/threonine-protein kinase with a critical role in starting the innate immune response to foreign pathogens. It participates in Toll-like receptor (TLR) and IL-1R signalling. On TLR activation, MYD88 rapidly recruits IRAK4 to the receptor-signalling complex, where it forms the Myddosome together with IRAK2. IRAK4 first phosphorylates IRAK1, which stimulates IRAK1 kinase activity and intensive autophosphorylation.
IRAK4 also phosphorylates the Pellino E3 ubiquitin ligases (PELI1, PELI2 and PELI3), promoting Pellino-mediated polyubiquitination of IRAK1. The ubiquitin-binding domain of IKBKG/NEMO then binds polyubiquitinated IRAK1. This brings the IRAK1-MAP3K7/TAK1-TRAF6 complex together with the NEMO-IKKA-IKKB complex. MAP3K7/TAK1 activates the IKKs (CHUK/IKKA and IKBKB/IKKB), leading to nuclear translocation and activation of NF-kappa-B. In an alternative route, IRAK4 phosphorylates TIRAP, promoting its ubiquitination and degradation. It also phosphorylates NCF1 and regulates NADPH oxidase activation after LPS stimulation, which suggests a similar mechanism during microbial infection.
The human IRAK4 gene encodes a cytoplasmic kinase of the protein kinase superfamily, in the TKL Ser/Thr protein kinase family, Pelle subfamily. HGNC places it in the interleukin 1 receptor associated kinase family, alongside IRAK1, IRAK2 and IRAK3. According to NCBI Gene, IRAK4 activates NF-kappaB in both the TLR and T-cell receptor signalling pathways and is essential for most innate immune responses. Mutations cause IRAK4 deficiency and recurrent invasive pneumococcal disease. Multiple transcript variants encoding different isoforms have been described. The mouse ortholog is Irak4.
IRAK4 is critical for initiating the innate immune response against foreign pathogens through TLR and IL-1R signalling.
IRAK4 phosphorylates IRAK1 and Pellino proteins, leading to TAK1 and IKK activation and NF-kappa-B nuclear translocation.
MYD88 recruits IRAK4 upon TLR activation to form the Myddosome with IRAK2, a key early signalling complex.
Mutations in IRAK4 cause IRAK4 deficiency and recurrent invasive pneumococcal disease.
IRAK4 is a serine/threonine kinase that starts innate immune signalling downstream of TLRs and IL-1R. Recruited by MYD88, it phosphorylates IRAK1 and Pellino proteins, which ultimately activates NF-kappa-B. It also phosphorylates TIRAP and NCF1, linking it to TIRAP degradation and NADPH oxidase regulation.
IRAK4 is the HGNC symbol for interleukin 1 receptor associated kinase 4, and NY-REN-64 is a listed alias. UniProt names the protein interleukin-1 receptor-associated kinase 4. NCBI Gene reports multiple transcript variants that encode different isoforms.
Mutations in the IRAK4 gene result in IRAK4 deficiency and recurrent invasive pneumococcal disease, according to NCBI Gene. The mouse ortholog is Irak4. Check the datasheet of any product for its validated reactivity.
Other IRAK family kinases that act alongside IRAK4 in Toll-like receptor and IL-1R signalling.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q9NWZ3; product specifications from Assay Genie datasheets.