The CD14 region spanning amino acids 57-64 is critical for interaction with the extracellular Toll-like receptor 2 domain.
CD14 has been shown to enhance Toll-like receptor 2 (TLR2)-mediated signaling in response to peptidoglycan. Anti-CD14 monoclonal antibody MEM-18, whose epitope was located at the amino acid residues 57-64, blocked the binding of sCD14 to the recombinant soluble form of the extracellular TLR2 domain (sTLR2). The deletion mutant sCD14Delta57-64 lacking the amino acid residues 57-64 failed to bind to sTLR2. Cotransfection of wild type mCD14 but not mCD14Delta57-64 with TLR2 enhanced NF-kappaB activation in response to peptidoglycan. These results indicate that the CD14 region spanning amino acids 57-64 is critical for interacting with TLR2 and enhancing TLR2-mediated peptidoglycan signaling.
Iwaki
Daisuke
D
Department of Biochemistry, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-ku, Sapporo 060-8556, Japan.
Nishitani
Chiaki
C
Mitsuzawa
Hiroaki
H
Hyakushima
Naoki
N
Sano
Hitomi
H
Kuroki
Yoshio
Y
D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D002460:Cell Line; D005110:Extracellular Space / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors / Q000737:chemistry* / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010457:Peptidoglycan / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013329:Structure-Activity Relationship; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors
D000596:Amino Acids; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D010457:Peptidoglycan; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors