Heterotrimeric G proteins physically associated with the lipopolysaccharide receptor CD14 modulate both in vivo and in vitro responses to lipopolysaccharide
Heterotrimeric G proteins physically associated with the lipopolysaccharide receptor CD14 modulate both in vivo and in vitro responses to lipopolysaccharide
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DOI：
10.1172/jci4317
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发表时间：
1998-12-01
影响因子：
15.9
通讯作者：
Finberg, RW
中科院分区：
文献类型：
--
作者：
Solomon, KR;Kurt-Jones, EA;Finberg, RW
内毒素(LPS)刺激单核/巨噬细胞产生细胞因子而引起的感染性休克是导致发病和死亡的主要原因。主要的单核/巨噬细胞内毒素受体是糖基磷脂酰肌醇(GPI)锚定的糖蛋白CD14。在这里，我们证明了CD14与G(I)/G(O)异三聚体G蛋白共沉淀。此外，我们还证明了异三聚体G蛋白在正常人单核细胞和培养细胞中特异性地调节CD14介导的、脂多糖诱导的丝裂原活化蛋白激酶(MAPK)的激活和细胞因子的产生。我们在这里报道了G蛋白结合肽保护大鼠免受脂多糖诱导的死亡，这表明GPI锚定的受体和它物理上与之相关的细胞内信号分子之间存在功能联系。
Septic shock induced by lipopolysaccharide (LPS) triggering of cytokine production from monocytes/macrophages is a major cause of morbidity and mortality. The major monocyte/macrophage LPS receptor is the glycosylphosphatidylinositol (GPI)-anchored glycoprotein CD14. Here we demonstrate that CD14 coimmunoprecipitates with G(i)/G(o) heterotrimeric G proteins. Furthermore, we demonstrate that heterotrimeric G proteins specifically regulate CD14-mediated, LPS-induced mitogen-activated protein kinase (MAPK) activation and cytokine production in normal human monocytes and cultured cells. We report here that a G protein binding peptide protects rats from LPS-induced mortality, suggesting a functional linkage between a GPI-anchored receptor and the intracellular signaling molecules with which it is physically associated.