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Requirement for a conserved Toll/interleukin-1 resistance domain protein in the Caenorhabditis elegans immune response.

http://www.ncbi.nlm.nih.gov/pubmed/15123841

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-kappaB 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.

Pubmed ID: 15123841 RIS Download

Mesh terms: Animals | Base Sequence | Caenorhabditis elegans | DNA Primers | Enzyme Activation | Gene Expression Regulation | Membrane Glycoproteins | Mitogen-Activated Protein Kinases | Receptors, Interleukin-1 | Signal Transduction | p38 Mitogen-Activated Protein Kinases

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Associated grants

  • Agency: NIAID NIH HHS, Id: AI52455
  • Agency: NIGMS NIH HHS, Id: GM48707

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