Aurora-A Phosphorylates, Activates, and Relocalizes the Small GTPase RalA

Aurora-A Phosphorylates, Activates, and Relocalizes the Small GTPase RalA
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DOI:
10.1128/mcb.00916-08
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发表时间:
2010-01-15
影响因子:
5.3
通讯作者:
Counter, Christopher M.
Counter, Christopher M.
中科院分区:
生物学2区
文献类型:
--
作者:
Lim, Kian-Huat;Brady, Donita C.;Counter, Christopher M.

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将细胞外信号传递到细胞的小GTd-Ras和促进正常有丝分裂的激酶Aurora-A都可能在人类肿瘤中被不适当地激活。在这里,我们表明Aurora-A与致癌Ras一起增强转化细胞的生长。此外,这种转化以及在某些情况下的肿瘤发生依赖于RalA的S194,这是一个已知的Aurora-A磷酸化位点。Aurora-A不仅促进RalA活化,而且促进从质膜的易位和效应蛋白RalBP 1的活化。综上所述,这些数据表明Aurora-A可能通过RalA会聚于致癌Ras信号传导。
The small GTPase Ras, which transmits extracellular signals to the cell, and the kinase Aurora-A, which promotes proper mitosis, can both be inappropriately activated in human tumors. Here, we show that Aurora-A in conjunction with oncogenic Ras enhances transformed cell growth. Furthermore, such transformation and in some cases also tumorigenesis depend upon S194 of RalA, a known Aurora-A phosphorylation site. Aurora-A promotes not only RalA activation but also translocation from the plasma membrane and activation of the effector protein RalBP1. Taken together, these data suggest that Aurora-A may converge upon oncogenic Ras signaling through RalA.