Premium
Signal transduction pathways activated by the IL‐1 receptor family: ancient signaling machinery in mammals, insects, and plants
Author(s) -
O'Neill Luke A. J.,
Greene Catherine
Publication year - 1998
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.63.6.650
Subject(s) - biology , signal transduction , microbiology and biotechnology , signal transducing adaptor protein , interleukin 1 receptor , receptor , kinase , immunology , genetics , interleukin , cytokine
Interleukin‐1 (IL‐1) is a central regulator of the immune and inflammatory responses. Recently, significant advances have been made in the area of IL‐1 receptors and IL‐1 signal transduction. A family of proteins has been described that share significant homology in their signaling domains with the Type I IL‐1 receptor (IL‐1RI). These include the IL‐1 receptor accessory protein (IL‐1AcP), which does not bind IL‐1 but is essential for IL‐1 signaling; a Drosophila protein Toll; a number of human Toll‐like receptors (hTLRs); the putative IL‐18/IL‐1‐γ receptor IL‐1Rrp (IL‐1 receptor‐related protein); and a number of plant proteins. All appear to be involved in host responses to injury and infection. These homologies also extend to novel signaling proteins implicated in IL‐1 action. Two IL‐1 receptor‐associated kinases, IRAK‐1 and IRAK‐2, which have homologs in Drosophila (Pelle) and plants (Pto), have been implicated in the activation of the transcription factor, nuclear factor κB (NF‐κB). IRAK‐1 has also been implicated in AP1 induction, Jun amino‐terminal kinase (JNK) activation, and IL‐2 induction. It recruits the adapter protein TRAF6 to the IL‐1 receptor complex via an interaction with IL‐1AcP. TRAF6 then relays the signal via NF‐κB‐inducing kinase (NIK) to two I‐κB kinases (IKK‐1 and ‐2), leading to NF‐κB activation. Progress has also been made on other IL‐1‐responsive kinases, including JNK and p38 MAP kinase, with the latter having a role in multiple responses to IL‐1. The remarkable conservation between diverse species indicates that the IL‐1 system represents an ancient signaling machine critical for responses to environmental stresses and attack by pathogens. J. Leukoc. Biol . 63: 650–657; 1998.