Autoinhibition of c-Abl
Autoinhibition of c-Abl
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DOI：
10.1016/s0092-8674(02)00623-2
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发表时间：
2002-01-25
期刊：
影响因子：
64.5
通讯作者：
Superti-Furga, G
中科院分区：
文献类型：
--
作者：
Pluk, H;Dorey, K;Superti-Furga, G
尽管多年的研究，负责调节c-Abl酪氨酸激酶的分子机制仍然难以捉摸。我们现在报告的抑制纯化的c-Abl在体外的催化活性，表明调节是一个内在的属性的分子。我们表明，N-末端80个残基与蛋白质的其余部分的相互作用介导的自动调节。这种N-末端“帽”是实现和维持抑制所必需的，其丢失将c-Abl转化为致癌蛋白并有助于BCR-Abl的失调。
Despite years of investigation, the molecular mechanism responsible for regulation of the c-Abl tyrosine kinase has remained elusive. We now report inhibition of the catalytic activity of purified c-Abl in vitro, demonstrating that regulation is an intrinsic property of the molecule. We show that the interaction of the N-terminal 80 residues with the rest of the protein mediates autoregulation. This N-terminal "cap" is required to achieve and maintain inhibition, and its loss turns c-Abl into an oncogenic protein and contributes to deregulation of BCR-Abl.