The annexin protein lipocortin 1 regulates the MAPK/ERK pathway
The annexin protein lipocortin 1 regulates the MAPK/ERK pathway
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DOI：
10.1074/jbc.274.53.37620
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发表时间：
1999-12-31
影响因子：
4.8
通讯作者：
Bryant, CE
中科院分区：
文献类型：
--
作者：
Alldridge, LC;Harris, HJ;Bryant, CE
脂皮质素1（膜联蛋白1）是一种钙和磷脂结合蛋白，可调节抗炎反应，包括脂多糖诱导的抗炎反应。为了研究脂皮质素1在调节脂多糖诱导的信号转导途径中的确切作用，我们产生了稳定的RAW 264.7巨噬细胞系，表达减少和增加的脂皮质素1蛋白。几个RAW 264.7克隆与脂皮质素1蛋白水平增加，显示组成性激活的丝裂原活化蛋白激酶细胞外信号调节激酶，这是下调后脂多糖治疗。相反，脂皮质素1蛋白表达降低的克隆表现出延长的细胞外信号调节激酶活性，脂多糖激活后。脂皮质素1特异性调节细胞外信号调节激酶途径的组分，因为脂皮质素1蛋白表达的变化对相关的促分裂原活化蛋白激酶p38和c-Jun N-末端激酶没有影响。脂皮质素1调节细胞外信号调节激酶途径的上游组分，并与衔接蛋白生长因子结合蛋白相关。细胞外信号调节激酶活性改变的下游后果独立于促炎转录因子核因子κ B。这些数据表明，脂皮质素1特异性调节细胞外信号调节激酶信号转导途径的近端信号传导组分，导致RAW巨噬细胞中生化功能的调节。
Lipocortin 1 (annexin 1) is a calcium- and phospholipid-binding protein that modulates anti-inflammatory responses including those induced by lipopolysaccharide. To investigate the precise role of lipocortin 1 in regulating the lipopolysaccharide-induced signal transduction pathways, we generated stable RAW 264.7 macrophage cell lines expressing decreased and increased lipocortin 1 protein. Several RAW 264.7 clones with increased lipocortin 1 protein levels showed constitutive activation of the mitogen-activated protein kinase extracellular signal-regulated kinase, which was down-regulated following lipopolysaccharide treatment. Conversely, clones with decreased lipocortin 1 protein expression showed prolonged extracellular signal-regulated kinase activity, following lipopolysaccharide activation. Lipocortin 1 specifically regulates the components of the extracellular signal-regulated kinase pathway, since changes in lipocortin 1 protein expression had no affect on the related mitogen-activated protein kinases p38 and c-Jun N-terminal kinase. Lipocortin 1 modulated upstream components of the extracellular signal-regulated kinase pathway and associated with the adaptor protein growth factor binding protein. The downstream consequences of altered extracellular signal-regulated kinase activity were independent of the proinflammatory transcription factor nuclear factor kappa B. These data indicate that Lipocortin 1 specifically regulates proximal signaling components of the extracellular signal-regulated kinase signal transduction pathway, resulting in the modulation of biochemical functions in RAW macrophages.