Toll-Like Receptor Pathway

Preferred Label : Toll-Like Receptor Pathway;

Alternative definition : BIOCARTA: The innate immune response responds in a general manner to factors present in invading pathogens. Bacterial factors such as lipopolysaccharides (LPS, endotoxin), bacterial lipoproteins, peptidoglycans, and also CpG nucleic acids activate innate immunity as well as stimulating the antigen-specific immune response and triggering the inflammatory response. Members of the toll-like receptor (TLR) gene family convey signals stimulated by these factors, activating signal transduction pathways that result in transcriptional regulation and stimulate immune function. TLR2 is activated by bacterial lipoproteins, TLR4 is activated by LPS, and TLR9 is activated by CpG DNA; peptidoglycan recognition protein (PGRP) is activated by peptidoglycan (PGN). The downstream signaling pathways used by these receptors are similar to that used by the IL-1 receptor, activating the IL-1 receptor associated kinase (IRAK) through the MyD88 adaptor protein, and signaling through TRAF-6 and protein kinase cascades to activate NF-kB and Jun. NF-kB and c-Jun activate transcription of genes such as the proinflammatory cytokines IL-1 and IL-12. Several reports have suggested that the functional outcomes of signaling via TLR2, TLR4, and PGRP are not equivalent. For example, while the LPS-induced, p38-dependent response was dependent upon PU.1 binding, the PGN-induced, p38 response was not. The intracellular receptor for PGN, PGRP, is conserved from insects to mammals. In insects, PGRP activates prophenoloxidase cascade, a part of the insect antimicrobial defense system. Because mammals do not have the prophenoloxidase cascade, its function in mammals is unknown. However, it was suggested that an identical protein Tag7 was a tumor necrosis factor-like (TNF-like) cytokine. PGRP/Tag7 possesses cytotoxicity and triggers intranucleosomal DNA fragmentation in target cells in the same way as many known members of the TNF family. Fragmentation of DNA is one of the characteristics of apoptosis. The possibility that in another system, PGRP/Tag7 would induce NF-kB activation, as observed for TRAIL (TNF-related apoptosis-inducing ligand) receptors cannot be ruled out. (This definition may be outdated - see the DesignNote.);

NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA Definition might be outdated or inaccurate. Please see the Terms and Conditions for Use at http://www.biocarta.com/.;

Biocarta ID : h_tollPathway;

Details

Origin ID

C39257;

UMLS CUI

C1519544;

Semantic type(s)
- Cell Function [UMLS semantic type]
has_gene_product_element
- Dual Specificity Mitogen-Activated Protein Kinase Kinase 3 [NCIt concept]
- Dual Specificity Mitogen-Activated Protein Kinase Kinase 4 [NCIt concept]
- Dual Specificity Mitogen-Activated Protein Kinase Kinase 6 [NCIt concept]
- ETS Domain-Containing Protein Elk-1 [NCIt concept]
- Inhibitor of Nuclear Factor Kappa-B Kinase Subunit Alpha [NCIt concept]
- Inhibitor of Nuclear Factor Kappa-B Kinase Subunit Beta [NCIt concept]
- Interferon-Induced, Double-Stranded RNA-Activated Protein Kinase [NCIt concept]
- Interleukin-1 Receptor-Associated Kinase 1 [NCIt concept]
- Mitogen-Activated Protein Kinase 14 [NCIt concept]
- Mitogen-Activated Protein Kinase 8 [NCIt concept]
- Mitogen-Activated Protein Kinase Kinase Kinase 1 [NCIt concept]
- Mitogen-Activated Protein Kinase Kinase Kinase 14 [NCIt concept]
- Mitogen-Activated Protein Kinase Kinase Kinase 7 [NCIt concept]
- Monocyte Differentiation Antigen CD14 [NCIt concept]
- NF-Kappa-B Inhibitor Alpha [NCIt concept]
- Peroxisome Proliferator-Activated Receptor Alpha [NCIt concept]
- Proto-Oncogene c-Fos [NCIt concept]
- TGF-Beta-Activated Kinase 1 and MAP3K7-Binding Protein 1 [NCIt concept]
- TNF Receptor-Associated Factor 6 [NCIt concept]
- Toll-Interacting Protein [NCIt concept]
- Toll-Like Receptor 1 [NCIt concept]
- Toll-Like Receptor 2 [NCIt concept]
- Toll-Like Receptor 3 [NCIt concept]
- Toll-Like Receptor 4 [NCIt concept]
- Toll-Like Receptor 5 [NCIt concept]
- Toll-Like Receptor 6 [NCIt concept]
- Toll-Like Receptor 7 [NCIt concept]
- Toll-Like Receptor 8 [NCIt concept]
- Toll-Like Receptor 9 [NCIt concept]
- Transcription Factor AP-1 [NCIt concept]
- Transcription Factor p65 [NCIt concept]
pathway_has_gene_element
- CD14 wt Allele [NCIt concept]
- CHUK wt Allele [NCIt concept]
- EIF2AK2 wt Allele [NCIt concept]
- ELK1 wt Allele [NCIt concept]
- FOS wt Allele [NCIt concept]
- IKBKB wt Allele [NCIt concept]
- IRAK1 wt Allele [NCIt concept]
- JUN wt Allele [NCIt concept]
- MAP2K3 wt Allele [NCIt concept]
- MAP2K4 wt Allele [NCIt concept]
- MAP2K6 wt Allele [NCIt concept]
- MAP3K1 wt Allele [NCIt concept]
- MAP3K14 wt Allele [NCIt concept]
- MAP3K7 wt Allele [NCIt concept]
- MAPK14 wt Allele [NCIt concept]
- MAPK8 wt Allele [NCIt concept]
- NFKBIA wt Allele [NCIt concept]
- PPARA wt Allele [NCIt concept]
- RELA wt Allele [NCIt concept]
- TAB1 wt Allele [NCIt concept]
- TLR1 wt Allele [NCIt concept]
- TLR2 wt Allele [NCIt concept]
- TLR3 wt Allele [NCIt concept]
- TLR4 wt Allele [NCIt concept]
- TLR5 wt Allele [NCIt concept]
- TLR6 wt Allele [NCIt concept]
- TLR7 wt Allele [NCIt concept]
- TLR8 wt Allele [NCIt concept]
- TLR9 wt Allele [NCIt concept]
- TOLLIP wt Allele [NCIt concept]
- TRAF6 wt Allele [NCIt concept]

Keyword's position in hierarchy(ies) :

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