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首页> 外文期刊>Nature >The Eps8 protein coordinates EGF receptor signalling through Rac and trafficking through Rab5
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The Eps8 protein coordinates EGF receptor signalling through Rac and trafficking through Rab5

机译：Eps8蛋白通过Rac协调EGF受体信号传导，并通过Rab5协调运输。

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How epidermal growth factor receptor (EGFR) signalling is linked to EGFR trafficking is largely unknown. Signalling and trafficking involve small GTPases of the Rho and Rab families, respectively. But it remains unknown whether the signalling relying on these two classes of GTPases is integrated, and, if it is, what molecular machinery is involved. Here we report that the protein Eps8 connects these signalling pathways. Eps8 is a substrate of the EGFR, which is held in a complex with Sos1 by the adaptor protein E3b1 (ref. 2), thereby mediating activation of Rac. Through its src homology-3 domain, Eps8 interacts with RN-tre. We show that RN-tre is a Rab5 GTPase-activating protein, whose activity is regulated by the EGFR. By entering in a complex with Eps8, RN-tre acts on Rab5 and inhibits internalization of the EGFR. Furthermore, RN-tre diverts Eps8 from its Rac-activating function, resulting in the attenuation of Rac signalling. Thus, depending on its state of association with E3b1 or RN-tre, Eps8 participates in both EGFR signalling through Rac, and trafficking through Rab5.
机译：表皮生长因子受体（EGFR）信号如何与EGFR交易相关联是未知的。信号和贩运分别涉及Rho和Rab家族的小GTP酶。但是，尚不清楚依赖于这两类GTP酶的信号传导是否已经整合，以及是否整合了分子机制。在这里我们报告蛋白质Eps8连接这些信号通路。 Eps8是EGFR的底物，它通过衔接蛋白E3b1（参考2）与Sos1形成复合物，从而介导Rac的激活。通过其src同源性3域，Eps8与RN-tre相互作用。我们显示，RN-tre是Rab5 GTPase激活蛋白，其活性受EGFR调节。通过与Eps8形成复合物，RN-tre作用于Rab5并抑制EGFR的内在化。此外，RN-tre转移了Eps8的Rac激活功能，导致Rac信号的衰减。因此，根据其与E3b1或RN-tre的缔合状态，Eps8既通过Rac参与EGFR信号传导，又通过Rab5参与运输。

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