IRAK4: The "master IRAK" critical for initiating immune responses

Thu, 06/19/2014 - 13:30

IRAK4, also known as Interleukin-1 receptor-associated kinase 4, is a serine/threonine-protein kinase that plays a critical role in initiating innate and adaptive immune responses against foreign pathogens. It activates NF-kappaB in both Toll-like receptor (TLR) and T-cell receptor (TCR) signaling pathways.

IRAK-4 belongs to a family of mammalian IRAKs that include IRAK-1 [11], IRAK-2 [12], and IRAK-M, also known as IRAK-3 [13]. Out of the four members in the mammalian IRAK family, IRAK-4 is considered to be the “master IRAK”, the only family member indispensable for IL-1R/TLR signaling. In humans, mutations resulting in IRAK-4 deficiency have been linked to susceptibility to bacterial infections, especially recurrent pyogenic bacterial infections. Though characterized functionally as a serine/threonine kinase, the crystal structures revealed that IRAK-4 contains characteristic structural features of both serine/threonine and tyrosine kinases, as well as additional novel attributes, including the unique tyrosine gatekeeper residue (1). A study using Novus’ IRAK4 Antibody NB500-597 has shown that prolonged stimulation of TLR2, TLR4, or TLR9 causes a down-regulation of IRAK-4 protein, which may be mediated through cleavage of IRAK-4 by a protease induced by the activation of nuclear factor-kappaB. (2) Another study using the same Novus IRAK4 antibody, NB100-1527, has suggested that IRAK-4 is an integral part of the IL-1R signaling cascade and is capable of transmitting signals both dependent on and independent of its kinase activity. (3)

Western Blot: IRAK4 Antibody Western Blot: IRAK4 Antibody

Expanding the spectrum of infections associated with IRAK-4 deficiency, it has been shown that immunity mediated by IRAK-4 seems to be crucial for both the containment of and the inflammatory response to Shigella sonnei meningitis infection in the intestinal mucosa. This study suggested that IRAK-4 deficiency and related disorders should be considered in patients with systemic shigellosis. (4)

Novus Biologicals offers IRAK4 reagents for your research needs including:


  1. PMID: 19689377
  2. PMID: 15258191
  3. PMID: 15292196
  4. PMID: 15825022

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