Aurora A is involved in central spindle assembly through phosphorylation of Ser 19 in P150Glued.

Aurora A is involved in central spindle assembly through phosphorylation of Ser 19 in P150Glued.
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DOI:
10.1083/jcb.201210060
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发表时间:
2013-04-01
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Prigent C
Prigent C
中科院分区:
其他
文献类型:
--
作者:
Reboutier D;Troadec MB;Cremet JY;Chauvin L;Guen V;Salaun P;Prigent C

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一种被ATP类似物1-Na-PP1特异性抑制的人Aurora A激酶允许剖析这种蛋白在中心纺锤体组装中的新角色。对Aurora A激酶功能的了解仅限于中期前事件,特别是中心体成熟、G2/M转变和有丝分裂纺锤体组装。极光A参与中期以后的事件只是因为适当的实验在技术上是困难的。我们在这里报告了第一个由化学遗传学技术设计的人类极光A激酶(AS-AURA)的设计。该激酶在生物化学和细胞内具有完全的功能,并被ATP类似物1-萘基-PP1(1-Na-PP1)迅速和特异性地抑制。通过用1-Na-PP1处理专门表达AS-AURA的细胞,我们发现Aurora A是通过P150Glued的Ser19的磷酸化在后期的中心纺锤体组装中所必需的。因此,本文描述了一个新的极光A函数,它发生在中后期转换之后,并为寻找和研究新的极光A函数提供了一个新的有力工具。
A human Aurora A kinase engineered to be specifically inhibited by the ATP analog 1-Na-PP1 allows dissection of a novel role for this protein in central spindle assembly. Knowledge of Aurora A kinase functions is limited to premetaphase events, particularly centrosome maturation, G2/M transition, and mitotic spindle assembly. The involvement of Aurora A in events after metaphase has only been suggested because appropriate experiments are technically difficult. We report here the design of the first human Aurora A kinase (as-AurA) engineered by chemical genetics techniques. This kinase is fully functional biochemically and in cells, and is rapidly and specifically inhibited by the ATP analogue 1-Naphthyl-PP1 (1-Na-PP1). By treating cells exclusively expressing the as-AurA with 1-Na-PP1, we discovered that Aurora A is required for central spindle assembly in anaphase through phosphorylation of Ser 19 of P150Glued. This paper thus describes a new Aurora A function that takes place after the metaphase-to-anaphase transition and a new powerful tool to search for and study new Aurora A functions.
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