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Human Interaction Network Ontology
Last uploaded:
June 27, 2014
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| Id | http://purl.obolibrary.org/obo/HINO_0009159
http://purl.obolibrary.org/obo/HINO_0009159
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|---|---|
| Preferred Name | Endocytosis of TLR4:MD2:LPS:CD14 |
| Definitions |
Edited: Shamovsky, V, 2012-05-25
Authored: Shamovsky, V, 2012-04-19
Reviewed: Granucci, Francesca, Zanoni, Ivan, 2012-11-13
Reviewed: D'Eustachio, P, 2012-05-25
Upon LPS stimulation TLR4 is internalized into endosomes where the signaling pathway is triggered through the adaptors TRAM and TRIF leading to the activation of IRF3 and induction of IFN-beta [Tanimuro N et al 2008; Kagan JC et al 2008]. While TLR4 translocation to endosomes is governed by known regulators of general endocytic processes such as dynamins and clathrin, other proteins that specifically regulate LPS-stimulated TLR4 endocytosis have been also identified [Husebye et al 2006; Kagan JC et al 2008; Zanoni I et al 2011]. Thus, CD14 has been implicated both in transporting LPS to TLR4 and in delivering TLR4 to an endosomal compartment. TLR4 translocation activated by CD14 appears to be Syk-mediated, and requires its downstream effector phospholipase C gamma 2 (PLCgamma2), which in turn induces a drop in the concentration of PIP2 required for endosomal sealing [Zanoni I et al 2011]. It has also been shown that PLCgamma2 induces inositol 1,4,5-trisphosphate (IP(3)) production and subsequent calcium (Ca2+) release. Released intracellular Ca2+ was reported to mediate TLR4 trafficking and subsequent activation of IRF3. [Aki D et al 2008; Chiang CY et al 2012].
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| Type | http://www.w3.org/2002/07/owl#Class |
All Properties
| label |
Endocytosis of TLR4:MD2:LPS:CD14
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|---|---|
| comment |
Edited: Shamovsky, V, 2012-05-25
Authored: Shamovsky, V, 2012-04-19
Reviewed: Granucci, Francesca, Zanoni, Ivan, 2012-11-13
Reviewed: D'Eustachio, P, 2012-05-25
Upon LPS stimulation TLR4 is internalized into endosomes where the signaling pathway is triggered through the adaptors TRAM and TRIF leading to the activation of IRF3 and induction of IFN-beta [Tanimuro N et al 2008; Kagan JC et al 2008]. While TLR4 translocation to endosomes is governed by known regulators of general endocytic processes such as dynamins and clathrin, other proteins that specifically regulate LPS-stimulated TLR4 endocytosis have been also identified [Husebye et al 2006; Kagan JC et al 2008; Zanoni I et al 2011]. Thus, CD14 has been implicated both in transporting LPS to TLR4 and in delivering TLR4 to an endosomal compartment. TLR4 translocation activated by CD14 appears to be Syk-mediated, and requires its downstream effector phospholipase C gamma 2 (PLCgamma2), which in turn induces a drop in the concentration of PIP2 required for endosomal sealing [Zanoni I et al 2011]. It has also been shown that PLCgamma2 induces inositol 1,4,5-trisphosphate (IP(3)) production and subsequent calcium (Ca2+) release. Released intracellular Ca2+ was reported to mediate TLR4 trafficking and subsequent activation of IRF3. [Aki D et al 2008; Chiang CY et al 2012].
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| prefLabel |
Endocytosis of TLR4:MD2:LPS:CD14
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| definition source |
Pubmed18233961
Pubmed22158869
Reactome, http://www.reactome.org
Pubmed18297073
Pubmed22078883
Pubmed16467847
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| prefixIRI |
HINO:0009159
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| seeAlso |
ReactomeREACT_121112
Reactome Database ID Release 432201293
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| subClassOf | |
| type | |
| has input | |
| has output |
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