Interleukin-1 Receptor-Associated Kinase (IRAK)

Sino Biological offers a comprehensive set of tools for interleukin-1 receptor-associated kinase related studies, including proteins, antibodies (rabbit mAbs, mouse mAbs, and rabbit pAbs), ELISA kits, and ORF cDNA clones. The interleukin-1 receptor-associated kinase is a family of protein  kinases, which mediate signal transduction downstream of the toll-like receptor (TLR) and IL-1 receptor (IL-1R) superfamilies. The interleukin-1 receptor-associated kinase family includes four members: IRK1, IRK2, IRK3, and IRK4.

Interleukin-1 Receptor-Associated Kinase (IRAK) Products

• IRAK4

Interleukin-1 Receptor-Associated Kinase (IRAK) Background

The interleukin-1 receptor-associated kinase is a family of kinases, which mediate signal transduction downstream of the toll-like receptor (TLR) and IL-1 receptor (IL-1R) superfamilies. The interleukin-1 receptor associated kinase family includes four members: IRK1, IRK2, IRK3, and IRK4.

The interleukin-1 receptor-associated kinase 1 (IRAK-1) is a critical protein kinase involved in innate immunity signaling processes. IRAK-1 is known to be not only involved in the inducible expression of pro-inflammatory mediators, but also in macrophage migration. IRAK1 is also partially responsible for IL1-induced upregulation of the transcription factor NF-kappa B. the role of NF-κB has been abundantly investigated in human tumors, and IRAK-1 has also been suggested a potential target for lung cancer chemopreventive strategies.

The interleukin-1 receptor-associated kinase 2 (IRAK-2) has been implicated in multiple TLR signaling pathways, because the overexpression of IRAK2 activates NF-kappa B. In a recent study, peritoneal macrophages from IRAK2-deficient mice showed impaired production of cytokines in response to multiple TLR ligands.

Interleukin-1 receptor–associated kinase 3 (IRAK-3), also known as Interleukin-1 receptor (IL-1R)–associated kinase M (IRAK-M), might plays a pivotal role in the process of endotoxin tolerance (ET) in human monocytes. In a recent study, IRAK-M has been demonstrated to selectively attenuate Pam3CSK4-induced p38 activation through an IRAK1 independent and MKP-1 dependent pathway.

Interleukin-1 receptor–associated kinase 4 (IRAK-4), a first proximal kinase downstream of IL-1R and most Toll-like receptors (TLRs), has been reported to be pivotal for receptor-induced signaling and proinflammatory mediator activation. Its deficiency leads to a defect in innate immunity that is primarily associated with infection with the gram-positive organisms Streptococcus pneumoniae and Staphylococcus aureus. Recent studies have demonstrated that IRAK-4 kinase activity is crucial for IL-1R– and TLR-mediated myeloid differentiation factor 88 (MyD88)–dependent signaling and expression of proinflammatory mediators in vitro.

Interleukin-1 Receptor-Associated Kinase (IRAK) Related Studies

1. Escoll P, et al. (2004) Rapid up-regulation of IRAK-M expression following a second endotoxin challenge in human monocytes and in monocytes isolated from septic patients. Biochem. Biophys. Res. Commun. 311 (2): 465–72.
2. Su J, et al. (2007) Differential regulation and role of interleukin-1 receptor associated kinase-M in innate immunity signaling. Cell. Signal. 19 (7): 1596–601.
3. Krause JC, et al. (2009) Very late-onset group B Streptococcus meningitis, sepsis, and systemic shigellosis due to interleukin-1 receptor-associated kinase-4 deficiency. Clin Infect Dis. 49(9):1393-6.
4. Koziczak-Holbro M, et al. (2009) The critical role of kinase activity of interleukin-1 receptor-associated kinase 4 in animal models of joint inflammation. Arthritis Rheum. 60(6):1661-71.
5. Wan Y, et al. (2009) nterleukin-1 receptor-associated kinase 2 is critical for lipopolysaccharide-mediated post-transcriptional control. J Biol Chem. 284(16):10367-75.
6. Behrens C, (2010) Expression of interleukin-1 receptor-associated kinase-1 in non-small cell lung carcinoma and preneoplastic lesions. Clin Cancer Res. 16(1):34-44.
7. Gan L,et al. (2010) Interleukin-1 Receptor-Associated Kinase-1 (IRAK-1) functionally associates with PKCepsilon and VASP in the regulation of macrophage migration. Mol Immunol. 47(6):1278-82.