Anti-IRAK4 Antibody Picoband® Fluoro488 Conjugated

IRAK-4 (interleukin-1 receptor-associated kinase 4), also called REN64, in the IRAK family, is a protein kinase involved in signaling innate immune responses from Toll-like receptors. It also supports signaling from T-cell receptors. Scott (2002) mapped the REN64/IRAK4 gene to chromosome 12 based on similarity between the REN64 sequence (GenBank AF155118) and a chromosome 12 clone (GenBank AC093012) . Functional analysis by Li et al. (2002) determined that IRAK4, like IRAK1 and Pelle, has auto- and cross-phosphorylation kinase activity. Precipitation and binding analyses showed weak interaction between IRAK4 and IRAK1, but IRAK4 did not interact with other IRAK family members. Overexpressed IRAK4 interacted with MYD88 and TRAF6 and activated mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NFKB) pathways.

Isoform 1 and isoform 4 are expressed in HTLV- 1-infected T-cell lines (at protein level) . Isoform 1 and isoform 2 are strongly expressed in HTLV-1-infected T-cell lines. Isoform 3 and isoform 4 are weakly expressed in HTLV-1-infected T-cell lines. .

Atherosclerosis, Cardiovascular, Cytokines, Immunology, Innate Immunity, Interleukins, Protein Phosphorylation, Ser/Thr Kinases, Signal Transduction, TLR Signaling, Vascular Inflammation

Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens. Involved in Toll-like receptor (TLR) and IL-1R signaling pathways (PubMed:17878374) . Is rapidly recruited by MYD88 to the receptor-signaling complex upon TLR activation to form the Myddosome together with IRAK2. Phosphorylates initially IRAK1, thus stimulating the kinase activity and intensive autophosphorylation of IRAK1. Phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2 and PELI3) to promote pellino- mediated polyubiquitination of IRAK1. Then, the ubiquitin-binding domain of IKBKG/NEMO binds to polyubiquitinated IRAK1 bringing together the IRAK1-MAP3K7/TAK1-TRAF6 complex and the NEMO-IKKA- IKKB complex. In turn, MAP3K7/TAK1 activates IKKs (CHUK/IKKA and IKBKB/IKKB) leading to NF-kappa-B nuclear translocation and activation. Alternatively, phosphorylates TIRAP to promote its ubiquitination and subsequent degradation. Phosphorylates NCF1 and regulates NADPH oxidase activation after LPS stimulation suggesting a similar mechanism during microbial infections. .

1. Day, N., Tangsinmankong, N., Ochs, H., Rucker, R., Picard, C., Casanova, J.-L., Haraguchi, S., Good, R. Interleukin receptor-associated kinase (IRAK-4) deficiency associated with bacterial infections and failure to sustain antibody responses. J. Pediat. 144: 524-526, 2004. 2. Li, S., Strelow, A., Fontana, E. J., Wesche, H. IRAK-4: a novel member of the IRAK family with the properties of an IRAK-kinase. Proc. Nat. Acad. Sci. 99: 5567-5572, 2002. 3. Scott, A. F. Personal Communication. Baltimore, Md. 4/25/2002.