Recruitment of the interleukin-1 receptor (IL-1RI)-associated kinase IRAK to the IL-1RI is redox regulated.

Abstract:

:Interleukin-1 signaling is initiated by recruitment of adapter proteins and kinases to the type I interleukin-1 receptor (IL-1RI). It is modulated by accompanying redox processes at various levels, such as (auto-) phosphorylation of the IL-1RI-associated kinase IRAK, the phosphorylation of IkappaB and translocation and transcriptional activity of NF-kappaB. Here we demonstrate that the thiol-modifying agents diamide, menadione, and phenylarsine oxide (PAO) block the recruitment of IRAK to the receptor without inhibiting kinase activity in the immunoprecipitated IL-1RI complex in the human epithelial cell line ECV304 and the murine T cell line EL-4. Inhibition of IRAK receptor association by menadione is reversible in a GSH-dependent manner, while the PAO effect proved to be irreversible. Phospholipid hydroperoxide glutathione peroxidase attenuates inhibition by menadione. Recruitment correlates with the presence of thiol groups in IRAK that were available for IAIT-labeling. We conclude that recruitment of IRAK to the IL-1RI is redox regulated by the glutathione system, a reduced status being a prerequisite for an appropiate IL-1 response.

journal_name

Biol Chem

journal_title

Biological chemistry

authors

Böl GF,Jurrmann N,Brigelius-Flohé R

doi

10.1515/BC.2003.068

keywords:

subject

Has Abstract

pub_date

2003-04-01 00:00:00

pages

609-17

issue

4

eissn

1431-6730

issn

1437-4315

journal_volume

384

pub_type

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