TIRAP: an adapter molecule in the Toll signaling pathway (original) (raw)

Nature Immunology volume 2, pages 835–841 (2001)Cite this article

Abstract

Mammalian Toll-like receptors (TLRs) recognize conserved products of microbial metabolism and activate NF-κB and other signaling pathways through the adapter protein MyD88. Although some cellular responses are completely abolished in MyD88-deficient mice, TLR4, but not TLR9, can activate NF-κB and mitogen-activated protein kinases and induce dendritic cell maturation in the absence of MyD88. These differences suggest that another adapter must exist that can mediate MyD88-independent signaling in response to TLR4 ligation. We have identified and characterized a Toll–interleukin 1 receptor (TIR) domain–containing adapter protein (TIRAP) and have shown that it controls activation of MyD88-independent signaling pathways downstream of TLR4. We have also shown that the double-stranded RNA-binding protein kinase PKR is a component of both the TIRAP- and MyD88-dependent signaling pathways.

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Acknowledgements

We thank S. Akira for MyD88-deficient mice; M. Katze and L. Jensen for p58 and IL-1R plasmids; and L. Kopp for helpful discussions and critical reading of the manuscript. Supported by NIH grant AI44220-01, the Searle Foundation (R. M.) and the Howard Hughes Medical Institute (R. M. and T. H.).

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  1. Tiffany Horng and Gregory M. Barton: These authors contributed equally to this work.

Authors and Affiliations

  1. Howard Hughes Medical Institute, Section of Immunobiology, Yale University School of Medicine, New Haven, 06520, CT, USA
    Tiffany Horng, Gregory M. Barton & Ruslan Medzhitov

Authors

  1. Tiffany Horng
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  2. Gregory M. Barton
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  3. Ruslan Medzhitov
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Correspondence toRuslan Medzhitov.

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Horng, T., Barton, G. & Medzhitov, R. TIRAP: an adapter molecule in the Toll signaling pathway.Nat Immunol 2, 835–841 (2001). https://doi.org/10.1038/ni0901-835

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