Toll and Toll-like proteins: an ancient family of receptors signaling infection.
Innate immunity is the first-line host defense of multicellular organisms that rapidly operates to limit infection upon exposure to microbes. It involves intracellular signaling pathways in the fruit-fly Drosophila and in mammals that show striking similarities. Recent genetic and biochemical data have revealed, in particular, that proteins of the Toll family play a critical role in the immediate response to infection. We review here the recent developments on the structural and functional characterization of this evolutionary ancient and important family of proteins, which can function as cytokine receptors (Toll in Drosophila) or pattern recognition receptors (TLR4 in mammals) and activate similar, albeit non identical signal transduction pathways, in flies and mammals.
Institute of Molecular and Cellular Biology, CNRS, Strasbourg, France.
J L
JL
Imler
J A
JA
Hoffmann
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000943:Antigens, Differentiation / Q000502:physiology; D001324:Autoantigens / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics / Q000254:growth & development / Q000276:immunology; D005786:Gene Expression Regulation; D020672:I-kappa B Proteins / Q000502:physiology; D007113:Immunity, Innate / Q000502:physiology*; D007239:Infections / Q000276:immunology*; D019476:Insect Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D053592:Interleukin-1 Receptor-Associated Kinases; D007814:Larva; D018950:Lipopolysaccharide Receptors / Q000502:physiology; D008070:Lipopolysaccharides / Q000276:immunology; D020935:MAP Kinase Signaling System / Q000502:physiology; D008322:Mammals / Q000235:genetics / Q000276:immunology; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D005810:Multigene Family; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B / Q000502:physiology; D010457:Peptidoglycan / Q000494:pharmacology; D010766:Phosphorylation; D011494:Protein Kinases / Q000502:physiology; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D011971:Receptors, Immunologic; D011993:Recombinant Fusion Proteins / Q000276:immunology; D015398:Signal Transduction / Q000502:physiology*; D013682:Teichoic Acids / Q000276:immunology; D051197:Toll-Like Receptor 4; D051198:Toll-Like Receptor 5; D051216:Toll-Like Receptor 6; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors; D014452:Ubiquitins / Q000378:metabolism
C094464:18w protein, Drosophila; D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D001324:Autoantigens; D015815:Cell Adhesion Molecules; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D020672:I-kappa B Proteins; D019476:Insect Proteins; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C499312:Myd88 protein, Drosophila; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D010457:Peptidoglycan; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D011993:Recombinant Fusion Proteins; D013682:Teichoic Acids; C068721:Tl protein, Drosophila; C495369:Tlr6 protein, mouse; C495370:Tlr9 protein, mouse; D051197:Toll-Like Receptor 4; D051198:Toll-Like Receptor 5; D051216:Toll-Like Receptor 6; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors; D014452:Ubiquitins; C495341:tehao protein, Drosophila; C009900:lipoteichoic acid; D011494:Protein Kinases; D053592:Interleukin-1 Receptor-Associated Kinases