toll-like receptor pathway
| PAG Title | toll-like receptor pathway |
| PAG ID | WAG001246 |
| Type | P |
| Source Link |  BioCarta |
| Publication Reference | NA |
| PAG Description | The inte 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 inte 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 sigls stimulated by these factors, activating sigl transduction pathways that result in transcriptiol regulation and stimulate immune function. TLR2 is activated by bacterial lipoproteins, TLR4 is activated by LPS, and TLR9 is activated by CpG D; peptidoglycan recognition protein (PGRP) is activated by peptidoglycan (PGN). The downstream sigling pathways used by these receptors are similar to that used by the IL-1 receptor, activating the IL-1 receptor associated kise (IRAK) through the MyD88 adaptor protein, and sigling through TRAF-6 and protein kise 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 recent reports have suggested that the functiol outcomes of sigling 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 intracelular 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 D fragmentation in target cells in the same way as many known members of the TNF family. Fragmentation of D 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 canot be ruled out. |
| Species | Homo sapiens |
| nCoCo Score | 4,503 |
| Base PAG ID | WAG001246 |
| Human Phenotyte Annotation | |
| Curator | PAGER curation team |
| Curator Contact | PAGER-contact@googlegroups.com |
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