Identification of B cell adaptor for PI3-kinase (BCAP) as an Abl interactor 1-regulated substrate of Abl kinases

Identification of B cell adaptor for PI3-kinase (BCAP) as an Abl interactor 1-regulated substrate of Abl kinases
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DOI:
10.1016/j.febslet.2005.04.052
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发表时间:
2005-06-06
期刊:
影响因子:
3.5
通讯作者:
Shishido, T
Shishido, T
中科院分区:
生物学3区
文献类型:
--
作者:
Maruoka, M;Suzuki, J;Shishido, T

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在之前的工作中,我们表明 AN 相互作用子 1 (Abi-1) 通过连接酶和底物,促进 c-Ab1 对哺乳动物启用 (Mena) 的磷酸化。为了确定这种机制是否扩展到其他 c-Ab1 底物,我们使用酵母双杂交系统来寻找与 Abi-1 相互作用的蛋白质。通过筛选人类白细胞 cDNA 文库,我们确定 BCAP(磷酸肌醇 3 激酶的 B 细胞接头)是另一种 Abi-1 相互作用蛋白。结合实验表明,Abi-1 的 SH3 结构域和 BCAP 的 C 端聚脯氨酸结构参与了两者之间的相互作用。在培养的细胞中,Abi-1不仅促进c-Ab1而且还促进v-Ab1对BCAP的磷酸化。 c-Ab1 对 BCAP 的磷酸化位点被定位到 C 末端区域的五个酪氨酸残基,这些残基在哺乳动物中非常保守。这些结果表明 Abi-1 促进 Ab1 介导的 BCAP 磷酸化,并表明 Abi-1 一般协调激酶-底物相互作用。 (c) 2005 年欧洲生化学会联合会。由 Elsevier B.V. 出版。保留所有权利。
In previous work we showed that AN interactor 1 (Abi-1), by linking enzyme and substrate, promotes the phosphorylation of Mammalian Enabled (Mena) by c-Ab1. To determine whether this mechanism extends to other c-Ab1 substrates, we used the yeast two-hybrid system to search for proteins that interact with Abi-1. By screening a human leukocyte cDNA library, we identified BCAP (B-cell adaptor for phosphoinositide 3-kinase) as another Abi-1-interacting protein. Binding experiments revealed that the SH3 domain of Abi-1 and the C-terminal polyproline structure of BCAP are involved in interactions between the two. In cultured cells, Abi-1 promoted phosphorylation of BCAP not only by c-Ab1 but also by v-Ab1. The phosphorylation sites of BCAP by c-Ab1 were mapped to five tyrosine residues in the C-terminal region that are well conserved in mammals. These results show that Abi-1 promotes Ab1-mediated BCAP phosphorylation and suggest that Abi-1 in general coordinates kinase-substrate interactions. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.