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髓样分化蛋白-2在识别和转导内毒素信号中的作用 被引量:7

The Role of MD-2 in The Process of Endotoxin Recognition and Signal Transduction
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摘要 脂多糖(LPS)通过TLR4介导细胞炎症反应.研究表明,髓样分化蛋白-2(MD-2)通过与TLR4形成复合物参与LPS诱导的细胞信号过程.TLR4/MD-2复合物中的MD-2结合LPS后,引起TLR4低聚化,进而激发下游信号.MD-2合成后,大部分在内质网/高尔基体和TLR4结合,然后以TLR4/MD-2复合物的形式在细胞表面表达.这既能调节TLR4的胞内分布,又能辅助TLR4识别LPS.还有一部分MD-2释放到血浆中,形成可溶性的MD-2(sMD-2).sMD-2在CD14参与下,能结合血浆中的LPS,形成LPS-sMD-2复合物从而辅助只表达TLR4而不表达MD-2的细胞识别LPS,但过度表达的sMD-2又能抑制LPS信号.MD-2在TLR4介导的内毒素识别和信号转导过程中发挥了重要的调控作用. Lipopolysaccharide(LPS) can induce cell inflammation through interacting with TLR4. Recent studies have revealed that MD-2 participate in the process of LPS induced signal transduction pathway by forming a complex with TLR4. After binding to the MD-2 of the TLR4/MD-2 complex, LPS can induce TLR4- oligomerization and activate the downstream signal pathway. After being synthesized, most MD-2 can bind to TLR4 at the endoplasmic reticulum/Golgi apparatus and expresse as TLR4/MD-2 complex at the cellular surface. Therefore MD-2 not only can regulate the distribution of TLR4 in the cytoplasm, but also help TLR4 to recognize LPS. Another part of MD-2 can be released into plasma as soluble MD-2(sMD-2). With the help of CDI4, sMD-2 would interact with LPS in the plasma to constitute LPS-sMD-2 complex, helping cell who express only TLR4, to recognize LPS, however excessive expressed sMD-2 would repress the LPS signal transduction pathway. In conclusion, MD-2 plays a crucially modulating role in the process of TLR4 mediated endotoxin recognition and signal transduction.
出处 《生物化学与生物物理进展》 SCIE CAS CSCD 北大核心 2007年第5期460-464,共5页 Progress In Biochemistry and Biophysics
基金 国家重点基础研究发展计划项目(973)(2002CB513005) 国家自然科学基金重点资助项目(30270538)~~
关键词 髓样分化蛋白-2(MD-2) TLR4 脂多糖(LPS) 信号转导 myeloid differentiation-2 (MD-2), Toll-like receptor 4 (TLR4), lipopolysaccharide (LPS), signal transduction
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参考文献21

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二级参考文献16

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