IRAK-4: a novel member of the IRAK family with the properties of an IRAK-kinase.

Article Details

Citation

Li S, Strelow A, Fontana EJ, Wesche H

IRAK-4: a novel member of the IRAK family with the properties of an IRAK-kinase.

Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5567-72.

PubMed ID
11960013 [ View in PubMed
]
Abstract

Toll/IL-1 receptor family members are central components of host defense mechanisms in a variety of species. One well conserved element in their signal transduction is Ser/Thr kinases, which couple early signaling events in a receptor complex at the plasma membrane to larger signalosomes in the cytosol. The fruit fly Drosophila melanogaster has one member of this family of kinases, termed Pelle. The complexity of this pathway is vastly increased in vertebrates, and several Pelle homologs have been described and termed IL-1 receptor-associated kinase (IRAK). Here we report the identification of a novel and distinct member of the IRAK family, IRAK-4. IRAK-4 is the closest human homolog to Pelle. Endogenous IRAK-4 interacts with IRAK-1 and TRAF6 in an IL-1-dependent manner, and overexpression of IRAK-4 can activate NF-kappa B as well as mitogen-activated protein (MAP) kinase pathways. Most strikingly, and in contrast to the other IRAKs, IRAK-4 depends on its kinase activity to activate NF-kappa B. In addition, IRAK-4 is able to phosphorylate IRAK-1, and overexpression of dominant-negative IRAK-4 is blocking the IL-1-induced activation and modification of IRAK-1, suggesting a role of IRAK-4 as a central element in the early signal transduction of Toll/IL-1 receptors, upstream of IRAK-1.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Interleukin-1 receptor-associated kinase 4Q9NWZ3Details
Interleukin-1 receptor-associated kinase 1P51617Details