CD209 (DC-SIGN) 信号通路
中文名称
通路描述
CD209（也称为 DC-SIGN，一种 DC 特异性胞内粘附分子 -3 非整合素）是一种 II 型跨膜 C 型凝集素受体，主要在树突状细胞（DCs）上表达。CD209 作为模式识别受体（PRR），可识别多种微生物和病原体，有助于产生病原体特异的免疫反应。CD209 与表达甘露糖的病原体相互作用，如结核分枝杆菌（Mycobacterium tuberculosis）和 HIV-1。它还作为粘附受体，与内皮细胞上的 ICAM2 和 T 细胞上的 ICAM3 相互作用。CD209 不仅作为独立的 PRR，还参与调节转录因子 NF-κB 水平的 Toll 样受体（TLR）信号。CLEC7A（Dectin-1）和 CD209（DC-SIGN）信号通过独立于 SYK 途径但整合于 NF-κB 激活水平的激酶 RAF1 调节 TLR 信号。CLEC7A 或 CD209 激活 RAF1 不会导致细胞外信号调节激酶 1（ERK1）/2 或丝裂原活化蛋白激酶 1（MEK1）/2 的激活，但会导致 RELA（p65）的磷酸化和随后的乙酰化。RELA 在 S276 位点磷酸化不仅通过乙酰化 p65 正调节 p65 活性，还通过将活性 RELB 隔离到不结合 DNA 的 p65-RELB 二聚体中抑制 RELB 活性。RAF1 依赖性信号通路对 Dectin-1 介导的免疫至关重要，它调节两种经典（促进 p65 磷酸化和乙酰化）和非经典（形成无活性的 p65-RELB 二聚体）NK-κB 激活。
英文描述
CD209 (DC-SIGN) signaling CD209 (also called as DC-SIGN (DC-specific intracellular adhesion molecule-3-grabbing non-integrin)) is a type II transmembrane C-type lectin receptor preferentially expressed on dendritic cells (DCs). CD209 functions as a pattern recognition receptor (PRR) that recognises several microorganisms and pathogens, contributing to generation of pathogen-tailored immune responses (Gringhuis & Geijtenbeek 2010, den Dunnen et al. 2009, Svajger et al. 2010). CD209 interacts with different mannose-expressing pathogens such as Mycobacterium tuberculosis and HIV-1 (Gringhuis et al. 2007, Geijtenbeek et al. 2000a). It also acts as an adhesion receptor that interacts with ICAM2 (intracellular adhesion molecule-2) on endothelial cells and ICAM3 on T cells (Geijtenbeek et al. 2000b,c). CD209 functions not only as an independent PRR, but is also implicated in the modulation of Toll-like receptor (TLR) signaling at the level of the transcription factor NF-kB (Gringhuis et al. 2009). CLEC7A (Dectin-1) and CD209 (DC-SIGN) signalling modulates Toll-like receptor (TLR) signalling through the kinase RAF1 that is independent of the SYK pathway but integrated with it at the level of NF-kB activation. The activation of RAF1 by CLEC7A or CD209 does not lead to activation of extracellular signal-regulated kinase 1 (ERK1)/2 or Mitogen-activated protein kinase kinase 1 (MEK1)/2 but leads to the phosphorylation and subsequent acetylation of RELA (p65). RELA phosphorylated on S276 not only positively regulates the activity of p65 through acetylation of p65, but also represses RELB activity by sequestering active RELB into inactive p65-RELB dimers that do not bind DNA (Gringhuis et al. 2007, Svajger et al. 2010, Jacque et al. 2005). RAF1-dependent signaling pathway is crucial in dectin-1 mediated immunity as it modulates both the canonical (promoting p65 phosphorylation and acetylation) and non-canonical (forming inactive p65-RELB dimers) NK-kB activation.
所含基因
18 个基因