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Department of Molecular Biology, Genentech, Inc., San Francisco, CA 94080
Human Toll-like receptor 2 (TLR2) is a signaling receptor that
responds to LPS and activates NF-
B. Here, we investigate further the
events triggered by TLR2 in response to LPS. We show that TLR2
associates with the high-affinity LPS binding protein membrane CD14 to
serve as an LPS receptor complex, and that LPS treatment enhances the
oligomerization of TLR2. Concomitant with receptor oligomerization, the
IL-1R-associated kinase (IRAK) is recruited to the TLR2 complex.
Intracellular deletion variants of TLR2 lacking C-terminal 13 or 141 aa
fail to recruit IRAK, which is consistent with the inability of these
mutants to transmit LPS cellular signaling. Moreover, both deletion
mutants could still form complexes with wild-type TLR2 and act in a
dominant-negative (DN) fashion to block TLR2-mediated signal
transduction. DN constructs of myeloid differentiation protein, IRAK,
TNF receptor-associated factor 6, and NF-B-inducing kinase, when
coexpressed with TLR2, abrogate TLR2-mediated NF-B activation. These
results reveal a conserved signaling pathway for TLR2 and IL-1Rs and
suggest a molecular mechanism for the inhibition of TLR2 by DN
variants.
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S. C. Dreskin, G. W. Thomas, S. N. Dale, and L. E. Heasley Isoforms of Jun Kinase Are Differentially Expressed and Activated in Human Monocyte/Macrophage (THP-1) Cells J. Immunol., May 1, 2001; 166(9): 5646 - 5653. [Abstract] [Full Text] [PDF]
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Q. Wang, R. Dziarski, C. J. Kirschning, M. Muzio, and D. Gupta Micrococci and Peptidoglycan Activate TLR2{right-arrow}MyD88{right-arrow}IRAK{right-arrow}TRAF{right-arrow}NIK{right-arrow}IKK{right-arrow}NF-{kappa}B Signal Transduction Pathway That Induces Transcription of Interleukin-8 Infect. Immun., April 1, 2001; 69(4): 2270 - 2276. [Abstract] [Full Text] [PDF]
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 J. M. Kyriakis and J. Avruch Mammalian Mitogen-Activated Protein Kinase Signal Transduction Pathways Activated by Stress and Inflammation Physiol Rev, April 1, 2001; 81(2): 807 - 869. [Abstract] [Full Text] [PDF]
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T. Kikuchi, T. Matsuguchi, N. Tsuboi, A. Mitani, S. Tanaka, M. Matsuoka, G. Yamamoto, T. Hishikawa, T. Noguchi, and Y. Yoshikai Gene Expression of Osteoclast Differentiation Factor Is Induced by Lipopolysaccharide in Mouse Osteoblasts Via Toll-Like Receptors J. Immunol., March 1, 2001; 166(5): 3574 - 3579. [Abstract] [Full Text] [PDF]
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P.-Y. Perera, T. N. Mayadas, O. Takeuchi, S. Akira, M. Zaks-Zilberman, S. M. Goyert, and S. N. Vogel CD11b/CD18 Acts in Concert with CD14 and Toll-Like Receptor (TLR) 4 to Elicit Full Lipopolysaccharide and Taxol-Inducible Gene Expression J. Immunol., January 1, 2001; 166(1): 574 - 581. [Abstract] [Full Text] [PDF]
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D. H. Wyllie, E. Kiss-Toth, A. Visintin, S. C. Smith, S. Boussouf, D. M. Segal, G. W. Duff, and S. K. Dower Evidence for an Accessory Protein Function for Toll-Like Receptor 1 in Anti-Bacterial Responses J. Immunol., December 15, 2000; 165(12): 7125 - 7132. [Abstract] [Full Text] [PDF]
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Hua Yang, J. M. Daun, J. R. Rose, W. J. Christ, F. Gusovsky, and J. C. Chow Examination of chlorpromazine and other amphipathic drugs on the activity of lipopolysaccharide antagonists, E5564 and E5531 Innate Immunity, December 1, 2000; 6(6): 447 - 452. [Abstract] [PDF]
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R. I. Tapping, S. Akashi, K. Miyake, P. J. Godowski, and P. S. Tobias Toll-Like Receptor 4, But Not Toll-Like Receptor 2, Is a Signaling Receptor for Escherichia and Salmonella Lipopolysaccharides J. Immunol., November 15, 2000; 165(10): 5780 - 5787. [Abstract] [Full Text] [PDF]
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M. M. Monick, A. B. Carter, D. M. Flaherty, M. W. Peterson, and G. W. Hunninghake Protein Kinase C {zeta} Plays a Central Role in Activation of the p42/44 Mitogen-Activated Protein Kinase by Endotoxin in Alveolar Macrophages J. Immunol., October 15, 2000; 165(8): 4632 - 4639. [Abstract] [Full Text] [PDF]
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S. Thoma-Uszynski, S. M. Kiertscher, M. T. Ochoa, D. A. Bouis, M. V. Norgard, K. Miyake, P. J. Godowski, M. D. Roth, and R. L. Modlin Activation of Toll-Like Receptor 2 on Human Dendritic Cells Triggers Induction of IL-12, But Not IL-10 J. Immunol., October 1, 2000; 165(7): 3804 - 3810. [Abstract] [Full Text] [PDF]
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K. M. Ardeshna, A. R. Pizzey, S. Devereux, and A. Khwaja The PI3 kinase, p38 SAP kinase, and NF-kappa B signal transduction pathways are involved in the survival and maturation of lipopolysaccharide-stimulated human monocyte-derived dendritic cells Blood, August 1, 2000; 96(3): 1039 - 1046. [Abstract] [Full Text] [PDF]
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M. Hirschfeld, Y. Ma, J. H. Weis, S. N. Vogel, and J. J. Weis Cutting Edge: Repurification of Lipopolysaccharide Eliminates Signaling Through Both Human and Murine Toll-Like Receptor 2 J. Immunol., July 15, 2000; 165(2): 618 - 622. [Abstract] [Full Text] [PDF]
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K. Tabeta, K. Yamazaki, S. Akashi, K. Miyake, H. Kumada, T. Umemoto, and H. Yoshie Toll-Like Receptors Confer Responsiveness to Lipopolysaccharide from Porphyromonas gingivalis in Human Gingival Fibroblasts Infect. Immun., June 1, 2000; 68(6): 3731 - 3735. [Abstract] [Full Text] [PDF]
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L. Caradonna, L. Amati, T. Magrone, N.M. Pellegrino, E. Jirillo, and D. Caccavo Invited review: Enteric bacteria, lipopolysaccharides and related cytokines in inflammatory bowel disease: biological and clinical significance Innate Immunity, June 1, 2000; 6(3): 205 - 214. [Abstract] [PDF]
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A. E. Medvedev, K. M. Kopydlowski, and S. N. Vogel Inhibition of Lipopolysaccharide-Induced Signal Transduction in Endotoxin-Tolerized Mouse Macrophages: Dysregulation of Cytokine, Chemokine, and Toll-Like Receptor 2 and 4 Gene Expression J. Immunol., June 1, 2000; 164(11): 5564 - 5574. [Abstract] [Full Text] [PDF]
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G. Scholz, K. Cartledge, and A. R. Dunn Hck Enhances the Adherence of Lipopolysaccharide-stimulated Macrophages via Cbl and Phosphatidylinositol 3-Kinase J. Biol. Chem., May 5, 2000; 275(19): 14615 - 14623. [Abstract] [Full Text] [PDF]
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 J. A. Thomas, R. L. Modlin, H. D. Brightbill, and P. J. Godowski Toll Genes and Responsiveness to Bacterial Endotoxins N. Engl. J. Med., March 2, 2000; 342(9): 664 - 665. [Full Text]
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T. K. Means, E. Lien, A. Yoshimura, S. Wang, D. T. Golenbock, and M. J. Fenton The CD14 Ligands Lipoarabinomannan and Lipopolysaccharide Differ in Their Requirement for Toll-Like Receptors J. Immunol., December 15, 1999; 163(12): 6748 - 6755. [Abstract] [Full Text] [PDF]
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M. N. Becker, G. Diamond, M. W. Verghese, and S. H. Randell CD14-dependent Lipopolysaccharide-induced beta -Defensin-2 Expression in Human Tracheobronchial Epithelium J. Biol. Chem., September 15, 2000; 275(38): 29731 - 29736. [Abstract] [Full Text] [PDF]
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S. H. Rhee and D. Hwang Murine TOLL-like Receptor 4 Confers Lipopolysaccharide Responsiveness as Determined by Activation of NFkappa B and Expression of the Inducible Cyclooxygenase J. Biol. Chem., October 27, 2000; 275(44): 34035 - 34040. [Abstract] [Full Text] [PDF]
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S. Frantz, R. A. Kelly, and T. Bourcier Role of TLR-2 in the Activation of Nuclear Factor kappa B by Oxidative Stress in Cardiac Myocytes J. Biol. Chem., February 9, 2001; 276(7): 5197 - 5203. [Abstract] [Full Text] [PDF]
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A. S. Kristof, J. Marks-Konczalik, and J. Moss Mitogen-activated Protein Kinases Mediate Activator Protein-1-dependent Human Inducible Nitric-oxide Synthase Promoter Activation J. Biol. Chem., March 9, 2001; 276(11): 8445 - 8452. [Abstract] [Full Text] [PDF]
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W. Ma, W. Lim, K. Gee, S. Aucoin, D. Nandan, M. Kozlowski, F. Diaz-Mitoma, and A. Kumar The p38 Mitogen-activated Kinase Pathway Regulates the Human Interleukin-10 Promoter via the Activation of Sp1 Transcription Factor in Lipopolysaccharide-stimulated Human Macrophages J. Biol. Chem., April 20, 2001; 276(17): 13664 - 13674. [Abstract] [Full Text] [PDF]
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 S. Tauszig, E. Jouanguy, J. A. Hoffmann, and J.-L. Imler From the Cover: Toll-related receptors and the control of antimicrobial peptide expression in Drosophila PNAS, September 12, 2000; 97(19): 10520 - 10525. [Abstract] [Full Text] [PDF]
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