Requirement for a conserved Toll/interleukin-1 resistance domain protein in the Caenorhabditis elegans immune response
| Autor: | Katherine A. Fitzgerald, Dennis H. Kim, Frederick M. Ausubel, Douglas T. Golenbock, Nicole T. Liberati, Rhonda L. Feinbaum |
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| Rok vydání: | 2004 |
| Předmět: |
Protein domain
Biology p38 Mitogen-Activated Protein Kinases digestive system RNA interference parasitic diseases Animals Caenorhabditis elegans Protein kinase A DNA Primers Regulation of gene expression Genetics Membrane Glycoproteins Multidisciplinary Innate immune system Base Sequence Receptors Interleukin-1 Signal transducing adaptor protein Biological Sciences biochemical phenomena metabolism and nutrition biology.organism_classification Cell biology Enzyme Activation Gene Expression Regulation Mitogen-Activated Protein Kinases Signal transduction Signal Transduction |
| Zdroj: | Proceedings of the National Academy of Sciences. 101:6593-6598 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0308625101 |
| Popis: | The p38 mitogen-activated protein kinase pathway regulates innate immune responses in evolutionarily diverse species. We have previously shown that the Caenorhabditis elegans p38 mitogen-activated protein kinase, PMK-1, functions in an innate immune response pathway that mediates resistance to a variety of microbial pathogens. Here, we show that tir-1, a gene encoding a highly conserved Toll/IL-1 resistance (TIR) domain protein, is also required for C. elegans resistance to microbial pathogens. RNA interference inactivation of tir-1 resulted in enhanced susceptibility to killing by pathogens and correspondingly diminished PMK-1 phosphorylation. Unlike all known TIR-domain adapter proteins, overexpression of the human TIR-1 homologue, SARM, in mammalian cells was not sufficient to induce expression of NF-κB or IRF3-dependent reporter genes that are activated by Toll-like receptor signaling. These data reveal the involvement of a previously uncharacterized, evolutionarily conserved TIR domain protein in innate immunity that is functionally distinct from other known TIR domain signaling adapters. |
| Databáze: | OpenAIRE |
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