Format

Send to

Choose Destination
See comment in PubMed Commons below
J Biol Chem. 1997 Aug 22;272(34):21540-7.

The interleukin-1 receptor-associated kinase is degraded by proteasomes following its phosphorylation.

Author information

1
Department of Inflammation Research, Merck Research Laboratories, Rahway, New Jersey 07065, USA.

Abstract

Following interleukin (IL)-1 stimulation, the majority of the cellular interleukin-1 receptor-associated kinase (IRAK) translocates to a discrete subset of the Type I IL-1 receptor (IL-1R1) in MRC-5 human lung fibroblasts. As the IRAK becomes multiphosphorylated, it is degraded by proteasomes at a rate comparable to that of the degradation of the phosphorylated IkappaBalpha protein. Proteasome inhibitors block the degradation of phosphorylated IRAK and correspondingly increase the amount of IL-1R1 that can be coimmunoprecipitated with IRAK. The nonspecific kinase inhibitor K-252b blocks IRAK phosphorylation and degradation, but does not inhibit IRAK association with the IL-1R1 indicating that translocation of IRAK to the IL-1R1 and its phosphorylation are independent events. The IL-1 specificity of these effects is indicated by the lack of IRAK phosphorylation and degradation by IL-1 in the presence of the IL-1 receptor antagonist or by the activation of MRC-5 cells by tumor necrosis factor alpha. Long term exposure of MRC-5 cells to IL-1 desensitizes the resynthesized IkappaBalpha to IL-1, but not to tumor necrosis factor alpha stimulation, but no additional effects on IRAK are seen.

PMID:
9261174
[Indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Support Center