The Interleukin-1 Receptor Accessory Protein (IL-1RAcP) Is Essential for IL-1-induced Activation of Interleukin-1 Receptor-associated Kinase (IRAK) and Stress-activated Protein Kinases (SAP Kinases)*
- From the Department of Molecular Pharmacology, Medical School Hannover, D-30623 Hannover, Germany and the
- ‡ Department of Internal Medicine, University of Regensburg, D-93042 Regensburg, Germany
- § To whom correspondence should be addressed: Dept. of Molecular Pharmacology, Medical School Hannover, D-30623 Hannover, Germany. Tel.: 49-511-532-4082; Fax: 49-511-532-4081; E-mail:VERBIN{at}VM.MHRZ.MH-HANNOVER.DE.
Abstract
Interleukin-1 (IL-1) is a central mediator of the immune system involved in acute and chronic inflammatory responses. Although the sequences of two types of IL-1 receptors are known, the exact molecular events resulting in signal transduction and coupling to downstream signaling elements remain unclear. The recently cloned IL-1 receptor accessory protein (IL-1RAcP) has been suggested as a co-receptor molecule for IL-1RI, supported by the observation that its expression correlates to IL-1 responsiveness. We transfected the EL-4 subline D6/76 with IL-1RAcP cDNA. This cell line is an IL-1 non-responder expressing IL-1RI but lacking constitutive IL-1RAcP expression. The expression of IL-1RAcP in EL-4 D6/76 was sufficient to restore IL-1-induced activation of interleukin-1 receptor-associated kinase and of stress-activated protein kinases, translocation of the transcription factors NFκB and IL-1 NF to the nucleus, and induction of IL-2 mRNA synthesis. These results proved that IL-1RAcP is an indispensible molecule in the IL-1 receptor signal transduction complex, necessary to link events on the plasma membrane level to downstream signaling pathways, allowing IL-1-dependent activation of transcription factors and gene expression.
Footnotes
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↵* The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵1 The abbreviations used are:
- IL
-
interleukin
- rh
-
recombinant human
- IRAK
-
interleukin-1 receptor-associated kinase
- SAPK
-
stress-activated protein kinase
- RT-PCR
-
reverse transcriptase-polymerase chain reaction
- PBS
-
phosphate-buffered saline
- GAPDH
-
glyceraldehyde-3-phosphate dehydrogenase
- PAGE
-
polyacrylamide gel electrophoresis
- DTT
-
dithiothreitol
- GST
-
glutathione S-transferase
- CHO
-
Chinese hamster ovary.
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↵2 H. Wesche and M. U. Martin, unpublished data.
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- Received November 5, 1996.
- Revision received January 17, 1997.
- © 1997 by The American Society for Biochemistry and Molecular Biology, Inc.
