Protein Phosphatase 1α Interacting Proteins in the Human Brain
Protein Phosphatase 1α Interacting Proteins in the Human Brain
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DOI：
10.1089/omi.2011.0041
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发表时间：
2012-02-01
影响因子：
3.3
通讯作者：
da Cruz e Silva, Edgar F.
中科院分区：
文献类型：
--
作者：
Esteves, Sara L. C.;Domingues, Sara C.;da Cruz e Silva, Edgar F.
蛋白磷酸酶1 （PP1）是一种主要的丝氨酸/苏氨酸磷酸酶，其活性依赖于与PP1相互作用蛋白（PIPs）的调节亚基的结合，PP1相互作用蛋白负责将PP1靶向到特定的细胞位置，指定其底物或调节其作用。目前，已有超过200种pip被描述为涉及PP1的细胞机制。此外，已经确定了几种pip是组织和事件特异性的。此外，PP1/PIP复合物的多样性还可以通过多种PP1同工异构体的存在来进一步实现，这些PP1同工异构体可以优先结合特定的PIP。因此，PP1/PIP复合物对细胞中的特定功能具有高度特异性，因此，它们是极好的药理学靶点。因此，通过高通量酵母双杂交方法对人类大脑中特异性PP1 α PIPs进行了深入调查。66种蛋白被识别为结合PP1 α，其中39种是新的pip。为了与PP1 α人脑酵母双杂交的结果进行整合，我们还进行了大型蛋白质相互作用数据库的检索，共检索到246种相互作用。
Protein Phosphatase 1 (PP1) is a major serine/threonine-phosphatase whose activity is dependent on its binding to regulatory subunits known as PP1 interacting proteins (PIPs), responsible for targeting PP1 to a specific cellular location, specifying its substrate or regulating its action. Today, more than 200 PIPs have been described involving PP1 in panoply of cellular mechanisms. Moreover, several PIPs have been identified that are tissue and event specific. In addition, the diversity of PP1/PIP complexes can further be achieved by the existence of several PP1 isoforms that can bind preferentially to a certain PIP. Thus, PP1/PIP complexes are highly specific for a particular function in the cell, and as such, they are excellent pharmacological targets. Hence, an in-depth survey was taken to identify specific PP1 alpha PIPs in human brain by a high-throughput Yeast Two-Hybrid approach. Sixty-six proteins were recognized to bind PP1 alpha, 39 being novel PIPs. A large protein interaction databases search was also performed to integrate with the results of the PP1 alpha Human Brain Yeast Two-Hybrid and a total of 246 interactions were retrieved.