Cutting edge:: The nucleotide receptor P2X7 contains multiple protein- and lipid-interaction motifs including a potential binding site for bacterial lipopolysaccharide
Cutting edge:: The nucleotide receptor P2X7 contains multiple protein- and lipid-interaction motifs including a potential binding site for bacterial lipopolysaccharide
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DOI：
10.4049/jimmunol.167.4.1871
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发表时间：
2001-08-15
影响因子：
4.4
通讯作者：
Bertics, PJ
中科院分区：
文献类型：
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作者：
Denlinger, LC;Fisette, PL;Bertics, PJ
核苷酸受体P2 X（7）已被证明可调节LPS诱导的巨噬细胞产生多种炎症介质。虽然P2 X7的C-末端部分被认为是多种受体功能所必需的，但关于位于该区域内的结构基序知之甚少。我们在这里表明，P2 X7的C-末端结构域包含几个明显的蛋白质-蛋白质和蛋白质-脂质相互作用的基序与潜在的重要性，巨噬细胞信号和LPS的行动。令人惊讶的是，P2 X7还含有保守的LPS结合结构域。在这份报告中，我们证明了来自这个P2 X7序列的肽在体外结合LPS。此外，这些肽中和LPS激活细胞外信号调节激酶（ERK 1、ERK 2）和促进RAW 264.7巨噬细胞中κ β-α同种型（I κ β-α）抑制剂降解的能力。总的来说，这些数据表明，P2 X7的C-末端结构域可以直接协调与巨噬细胞功能和LPS作用相关的几个信号转导事件。
The nucleotide receptor P2X(7) has been shown to modulate LPS-induced macrophage production of numerous inflammatory mediators. Although the C-terminal portion of P2X7 is thought to be essential for multiple receptor functions, little is known regarding the structural motifs that lie within this region. We show here that the P2X7 C-terminal domain contains several apparent protein-protein and protein-lipid interaction motifs with potential importance to macrophage signaling and LPS action. Surprisingly, P2X7 also contains a conserved LPS-binding domain. In this report, we demonstrate that peptides derived from this P2X7 sequence bind LPS in vitro. Moreover, these peptides neutralize the ability of LPS to activate the extracellular signal-regulated kinases (ERK1, ERK2) and to promote the degradation of the inhibitor of kappa beta-alpha isoform (I kappa beta-alpha) in RAW 264.7 macrophages. Collectively, these data suggest that the C-terminal domain of P2X7 may directly coordinate several signal transduction events related to macrophage unction and LPS action.