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Pathway Description
Toll-Like Receptor Pathway 1
Homo sapiens
Category:
Protein Pathway
Sub-Categories:
Immunological
Pathogen-Activated Signaling
Gene Regulatory
Cellular Response
Created: 2018-07-30
Last Updated: 2019-08-16
Toll-like receptors (TLRs) are part of the innate immune system. These receptors recognize pathogen-associated molecular patterns from different microbes. TLR2 recognizes a variety of PAMPs including lipoproteins, peptidoglycans, lipotechoic acids, and mannan. TLR3 recognizes viral double-stranded RNA, small interfering RNAsa, and self-RNAs. TLR4 recognizes lipopolysaccharides. TLR7 recognizes single-stranded RNA. TLR9 recognizes bacterial and viral DNA with unmethylated CpG-DNA motifs. TLRs are synthesized in the endoplasmic reticulum, moved to the Golgi, and then recruited to the cell surface or intracellular compartments. TLRs recruit adaptor molecules such as MYD88, TRIF, TIRAP, or TRAM leading to the activation of transcription factors NF-kappa-B causing innate immune responses. MYD88 is recruited by all TLRs. Adaptor TIRAP recruits MYD88 to cell surface TLRs, including TLR2 and TLR4. TLR signaling molecule IRAK1 activation activates TRAF6 causing the activation of IKK complex then NF-kappa-B and kinases. Activated TRAF6 promotes polyubiquination of TRAF6 and TAK1, TAB1, TAB2 complex. TAK1 activates pathways causing activation of IKK complex and NF-kappa-B and MAPK pathways. The IKK complex phosphorylates and activates IKK-beta. IKK complex also phosphorylates I-kappa-B-alpha allowing dissociation and translocation of NF-kappa-B to the nucleus resulting in proinflammatory gene expression. Activated TAK1 complex also activates p38 and JNK, regulating the activation of AP-1 transcription factors to regulate inflammatory responses. Many transmembrane molecules, such as glycophosphatidylinositol-anchored protein CD14, also regulate TLR signaling pathways.
References
Toll-Like Receptor Pathway 1 References
https://cgap.nci.nih.gov/Pathways/BioCarta/h_tollPathway
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