Epidermal growth factor-mediated caveolin recruitment to early endosomes and MAPK activation -: Role of cholesterol and actin cytoskeleton
Epidermal growth factor-mediated caveolin recruitment to early endosomes and MAPK activation -: Role of cholesterol and actin cytoskeleton
复制标题
DOI：
10.1074/jbc.m001131200
复制
发表时间：
2000-09-29
影响因子：
4.8
通讯作者：
Enrich, C
中科院分区：
文献类型：
--
作者：
Pol, A;Lu, A;Enrich, C
真核细胞的内吞区室是一种复杂的细胞内结构，参与多种内化分子的分选、加工和降解。近年来，细胞膜小窝摄取作为一种替代性的内化途径出现，似乎与某些信号转导途径直接相关。然而，调节小窝蛋白从细胞表面转运到内吞区室的机制、分子和结构在很大程度上是未知的。在这项研究中，正常静止的成纤维细胞（正常大鼠肾（NRK））被用来证明，表皮生长因子导致部分小窝蛋白从细胞表面重新分配到一个cellubrevin早期内吞隔室。用细胞松弛素D或latrunculin A处理NRK细胞抑制该途径以及伴随的Mek和有丝分裂活化蛋白（MAP）激酶的活化;然而，如果用菲律宾肽预处理细胞，则细胞松弛素D不抑制由表皮生长因子诱导的MAP激酶的磷酸化。从这些结果中，我们得出结论，在NRK细胞中，完整的肌动蛋白细胞骨架是必要的EGF介导的运输小窝蛋白从细胞表面进入早期内吞隔室和激活MAP激酶途径。
The endocytic compartment of eukaryotic cells is a complex intracellular structure involved in sorting, processing, and degradation of a great variety of internalized molecules. Recently, the uptake through caveolae has emerged as an alternative internalization pathway, which seems to be directly related with some signal transduction pathways. However, the mechanisms, molecules, and structures regulating the transport of caveolin from the cell surface into the endocytic compartment are largely unknown. In this study, normal quiescent fibroblasts (normal rat kidney (NRK)) were used to demonstrate that epidermal growth factor causes partial redistribution of caveolin from the cell surface into a cellubrevin early endocytic compartment. Treatment of NRK cells with cytochalasin D or latrunculin A inhibits this pathway and the concomitant activation of Mek and mitotic-activated protein (MAP) kinase; however, if cells were pre-treated with filipin, cytochalasin D does not inhibit the phosphorylation of MAP kinase induced by epidermal growth factor. From these results we conclude that in NRK cells the intact actin cytoskeleton is necessary for the EGF-mediated transport of caveolin from the cell surface into the early endocytic compartment and the activation of MAP kinase pathway.