TIRAP: an adapter molecule in the Toll signaling pathway

Nat Immunol. 2001 Sep;2(9):835-41. doi: 10.1038/ni0901-835.

Abstract

Mammalian Toll-like receptors (TLRs) recognize conserved products of microbial metabolism and activate NF-kappa B 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-kappa B 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Animals
  • Antigens, Differentiation / metabolism
  • Cell Differentiation
  • Cell Line
  • Cloning, Molecular
  • CpG Islands
  • Dendritic Cells / immunology
  • Drosophila Proteins*
  • HSP40 Heat-Shock Proteins
  • Humans
  • Lipopolysaccharides / pharmacology
  • Membrane Glycoproteins / antagonists & inhibitors
  • Membrane Glycoproteins / metabolism
  • Mice
  • Molecular Sequence Data
  • Mutation
  • Myeloid Differentiation Factor 88
  • Receptors, Cell Surface / antagonists & inhibitors
  • Receptors, Cell Surface / metabolism
  • Receptors, Cell Surface / physiology*
  • Receptors, Immunologic*
  • Receptors, Interleukin-1 / genetics*
  • Receptors, Interleukin-1 / physiology*
  • Sequence Homology, Amino Acid
  • Signal Transduction*
  • Toll-Like Receptor 4
  • Toll-Like Receptor 9
  • Toll-Like Receptors
  • eIF-2 Kinase / physiology

Substances

  • Adaptor Proteins, Signal Transducing
  • Antigens, Differentiation
  • DNAJC3 protein, human
  • Drosophila Proteins
  • HSP40 Heat-Shock Proteins
  • Lipopolysaccharides
  • MYD88 protein, human
  • Membrane Glycoproteins
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Receptors, Cell Surface
  • Receptors, Immunologic
  • Receptors, Interleukin-1
  • TIRAP protein, human
  • TIRAP protein, mouse
  • TLR4 protein, human
  • TLR9 protein, human
  • Toll-Like Receptor 4
  • Toll-Like Receptor 9
  • Toll-Like Receptors
  • eIF-2 Kinase

Associated data

  • GENBANK/AF378129
  • GENBANK/AF378130