Genome-wide analysis of human kinases in clathrin- and caveolae/raft-mediated endocytosis
Genome-wide analysis of human kinases in clathrin- and caveolae/raft-mediated endocytosis
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DOI：
10.1038/nature03571
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发表时间：
2005-07-07
期刊：
影响因子：
64.8
通讯作者：
Zerial, M
中科院分区：
文献类型：
--
作者：
Pelkmans, L;Fava, E;Zerial, M
内吞作用是一个关键的细胞过程，包含不同的进入途径和内吞小室。细胞信号传导机制在多大程度上对内吞作用进行高阶调控仍不清楚。利用高通量RNA干扰和自动图像分析，我们探究了人类激酶在两种主要内吞作用类型中的功能：网格蛋白介导的内吞作用以及小窝/脂筏介导的内吞作用。我们通过水疱性口炎病毒、猿猴病毒40的感染以及转铁蛋白运输进行监测，同时也通过细胞增殖和凋亡检测来进行。在此我们表明，大量的激酶参与内吞作用，并且每种内吞途径都由特定的激酶亚群调控。值得注意的是，一组激酶对两种内吞途径产生相反的作用，这表明存在协同调控。我们的分析表明，诸如控制细胞黏附、生长和增殖等信号传导功能在内吞作用机制中的整合程度比之前所认识到的要高得多。
Endocytosis is a key cellular process, encompassing different entry routes and endocytic compartments. To what extent endocytosis is subjected to high-order regulation by the cellular signalling machinery remains unclear. Using high-throughput RNA interference and automated image analysis, we explored the function of human kinases in two principal types of endocytosis: clathrin- and caveolae/raft-mediated endocytosis. We monitored this through infection of vesicular stomatitis virus, simian virus 40 and transferrin trafficking, and also through cell proliferation and apoptosis assays. Here we show that a high number of kinases are involved in endocytosis, and that each endocytic route is regulated by a specific kinase subset. Notably, one group of kinases exerted opposite effects on the two endocytic routes, suggesting coordinate regulation. Our analysis demonstrates that signalling functions such as those controlling cell adhesion, growth and proliferation, are built into the machinery of endocytosis to a much higher degree than previously recognized.