Phosphorylation of TPX2 by Plx1 enhances activation of Aurora A
Phosphorylation of TPX2 by Plx1 enhances activation of Aurora A
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DOI：
10.4161/cc.8.15.9086
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发表时间：
2009-08-01
期刊：
影响因子：
4.3
通讯作者：
Maller, James L.
中科院分区：
文献类型：
--
作者：
Eckerdt, Frank;Pascreau, Gaetan;Maller, James L.
进入有丝分裂需要激活有丝分裂激酶，包括Aurora A和polo样激酶1 （Plk1）。这些激酶水平的增加经常被发现与人类癌症有关，因此了解导致它们激活的过程是必要的。我们证明TPX2可以直接激活Aurora A，但Ajuba和inhibitor2都不能。此外，在卵母细胞成熟过程中，Plx1可以在体内间接诱导Aurora A t环磷酸化。我们发现TPX2中的Ser204是Plx1磷酸化位点。将Ser204突变为丙氨酸会降低Aurora A的激活，而拟磷Asp突变体则表现出增强的激活能力。最后，我们发现TPX2与Plx1的磷酸化增加了其激活Aurora A的能力。综上所述，我们的数据表明，Plx1很可能通过TPX2促进了Aurora A的激活。根据目前的文献，我们提出了一个模型，其中Plx1和Aurora a在一个正反馈回路中相互激活。
Entry into mitosis requires the activation of mitotic kinases, including Aurora A and Polo-like kinase 1 (Plk1). Increased levels of these kinases are frequently found associated with human cancers, and therefore it is imperative to understand the processes leading to their activation. We demonstrate that TPX2, but neither Ajuba nor Inhibitor-2, can activate Aurora A directly. Moreover, Plx1 can induce Aurora A T-loop phosphorylation indirectly in vivo during oocyte maturation. We identify Ser204 in TPX2 as a Plx1 phosphorylation site. Mutating Ser204 to alanine decreases activation of Aurora A, whereas a phosphomimetic Asp mutant exhibits enhanced activating ability. Finally, we show that phosphorylation of TPX2 with Plx1 increases its ability to activate Aurora A. Taken together, our data indicate that Plx1 promotes activation of Aurora A, most likely through TPX2. In light of the current literature, we propose a model in which Plx1 and Aurora A activate each other in a positive feedback loop.