极光激酶-A 使小 GTP 酶 RalA 磷酸化、激活并重新定位。
Aurora-A phosphorylates, activates, and relocalizes the small GTPase RalA.
机构信息
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
出版信息
Mol Cell Biol. 2010 Jan;30(2):508-23. doi: 10.1128/MCB.00916-08. Epub 2009 Nov 9.
Abstract
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.
摘要
小分子 GTP 酶 Ras 将细胞外信号传递到细胞内，激酶 Aurora-A 促进有丝分裂的正常进行，但这两者在人类肿瘤中都可能被异常激活。在这里，我们发现 Aurora-A 与致癌性 Ras 协同作用，增强了转化细胞的生长。此外，这种转化，在某些情况下还包括肿瘤发生，取决于 RalA 的 S194，这是一个已知的 Aurora-A 磷酸化位点。Aurora-A 不仅促进 RalA 的激活，还促进其从质膜易位以及效应蛋白 RalBP1 的激活。综上所述，这些数据表明，Aurora-A 可能通过 RalA 与致癌性 Ras 信号传导相融合。
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