Requirement for a conserved Toll/interleukin-1 resistance domain protein in the Caenorhabditis elegans immune response
Authors
Liberati, Nicole TFitzgerald, Katherine A.
Kim, Dennis H.
Feinbaum, Rhonda
Golenbock, Douglas T.
Ausubel, Frederick M.
UMass Chan Affiliations
Department of Medicine, Division of Infectious Diseases and ImmunologyDocument Type
Journal ArticlePublication Date
2004-05-05Keywords
AnimalsBase 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
Immunology and Infectious Disease
Metadata
Show full item recordAbstract
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.Source
Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6593-8. Link to article on publisher's siteDOI
10.1073/pnas.0308625101Permanent Link to this Item
http://hdl.handle.net/20.500.14038/35258PubMed ID
15123841Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1073/pnas.0308625101