Hepatocyte growth factor-induced Ras activation requires ERM proteins linked to both CD44v6 and F-Actin
Hepatocyte growth factor-induced Ras activation requires ERM proteins linked to both CD44v6 and F-Actin
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DOI：
10.1091/mbc.e06-08-0674
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发表时间：
2007-01-01
影响因子：
3.3
通讯作者：
Ponta, Helmut
中科院分区：
文献类型：
--
作者：
Orian-Rousseau, Veronique;Morrison, Helen;Ponta, Helmut
在几种类型的细胞中，受体酪氨酸激酶c-Met通过其配体肝细胞生长因子（HGF）的激活需要辅助受体CD 44 v6。CD 44细胞外结构域是c-Met自身磷酸化所必需的，而细胞内结构域是信号转导所必需的。我们已经表明，CD 44胞质尾区将ezrin、radixin和moesin（ERM）蛋白募集到CD 44 v6、c-Met和HGF的复合物中。我们现在已经确定了ERM蛋白的功能和它们在信号级联中促进的步骤。ERM蛋白与辅助受体的关联是绝对需要的，以介导鸟嘌呤核苷酸交换因子Sos对Ras的HGF依赖性激活。此外，ERM蛋白需要连接到肌动蛋白细胞骨架以催化Ras的活化。因此，我们在这里描述一个新的功能的细胞骨架。它是“信号体”复合物的一部分，该复合物组织Ras被Sos激活。到目前为止，细胞骨架主要被认为是信号转导的“应答者”。在这里，我们现在表明，F-肌动蛋白作为一个“诱导剂”，积极组织的信号级联。
In several types of cells, the activation of the receptor tyrosine kinase c-Met by its ligand hepatocyte growth factor (HGF) requires the coreceptor CD44v6. The CD44 extracellular domain is necessary for c-Met autophosphorylation, whereas the intracellular domain is required for signal transduction. We have already shown that the CD44 cytoplasmic tail recruits ezrin, radixin and moesin (ERM) proteins to the complex of CD44v6, c-Met, and HGF. We have now defined the function of the ERM proteins and the step they promote in the signaling cascade. The association of ERM proteins to the coreceptor is absolutely required to mediate the HGF-dependent activation of Ras by the guanine nucleotide exchange factor Sos. The ERM proteins need, in addition, to be linked to the actin cytoskeleton to catalyze the activation of Ras. Thus, we describe here a new function of the cytoskeleton. It is part of a "signalosome" complex that organizes the activation of Ras by Sos. So far the cytoskeleton has mainly been identified as a "responder" to signal transduction. Here, we show now that F-actin acts as an "inducer" that actively organizes the signaling cascade.