Department of Medicine, Division of Infectious Diseases and Immunology
Antibodies, Monoclonal; Cell Line; Cell Membrane; Cytokines; Extracellular Space; Humans; Intracellular Fluid; Leukocytes, Mononuclear; Membrane Glycoproteins; NF-kappa B; Protein Structure, Tertiary; Receptors, Cell Surface; Recombinant Fusion Proteins; Signal Transduction; Toll-Like Receptor 1; Toll-Like Receptor 2; Toll-Like Receptors; Zymosan
Cell and Developmental Biology | Immunology and Infectious Disease
Recognition of ligands by toll-like receptor (TLR) 2 requires interactions with other TLRs. TLRs form a combinatorial repertoire to discriminate between the diverse microbial ligands. Diversity results from extracellular and intracellular interactions of different TLRs. This paper demonstrates that TLR1 and TLR2 are required for ara-lipoarabinomannan- and tripalmitoyl cysteinyl lipopeptide-stimulated cytokine secretion from mononuclear cells. Confocal microscopy revealed that TLR1 and TLR2 cotranslationally form heterodimeric complexes on the cell surface and in the cytosol. Simultaneous cross-linking of both receptors resulted in ligand-independent signal transduction. Using chimeric TLRs, we found that expression of the extracellular domains along with simultaneous expression of the intracellular domains of both TLRs was necessary to achieve functional signaling. The domains from each receptor did not need to be contained within a single contiguous protein. Chimeric TLR analysis further defined the toll/IL-1R domains as the area of crucial intracellular TLR1-TLR2 interaction.
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Citation: J Cell Biol. 2003 Sep 15;162(6):1099-110. Link to article on publisher's site
Sandor, Frantisek; Latz, Eicke; Re, Fabio; Mandell, Leisa; Repik, Galina; Golenbock, Douglas T.; Espevik, Terje; Kurt-Jones, Evelyn A.; and Finberg, Robert W., "Importance of extra- and intracellular domains of TLR1 and TLR2 in NFkappa B signaling" (2003). Open Access Articles. Paper 920.