Regulating the regulator: Insights into the cardiac protein phosphatase 1 interactome.
Regulating the regulator: Insights into the cardiac protein phosphatase 1 interactome.
复制标题
调节调节剂：对心脏蛋白磷酸酶1相互作用的见解。
DOI：
10.1016/j.yjmcc.2016.09.009
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发表时间：
2016-12
影响因子：
5
通讯作者：
Wehrens, Xander H. T.
中科院分区：
文献类型：
--
作者：
Chiang, David Y.;Heck, Albert J. R.;Dobrev, Dobromir;Wehrens, Xander H. T.
蛋白质的可逆磷酸化是一种微妙而又动态平衡的蛋白激酶和磷酸酶之间的行为，它的紊乱是许多疾病过程的基础。虽然我们对蛋白激酶的了解在过去几十年里有了很大的增长，但对蛋白磷酸酶的了解相对较少。这可能是因为蛋白激酶数量多，功能相对特异，因此易于单独研究，而蛋白磷酸酶则少得多，功能更不特异。为了实现亚细胞定位和底物专一性，磷酸酶依赖于与大量的调节亚基、蛋白质支架和/或其他相互作用因子的合作。这一增加的复杂性给他们的研究带来了重大障碍，但也为新的药物干预提供了尚未探索的机会。本文主要介绍在心脏生理学和病理生理学中起重要作用的丝氨酸/苏氨酸蛋白磷酸酶-1(PP1)。尽管对PP1在包括心房颤动和心力衰竭在内的心脏疾病中的作用进行了大量的研究，但这些研究大多局限于对PP1催化亚单位(S)的检测和操纵，而没有充分考虑PP1的相互作用，这赋予了PP1‘S功能的特异性。为了补充这些研究，已经开发了三种无偏见的方法并应用于PP1相互作用组的作图：生物信息学方法、酵母双杂交筛选和亲和纯化质谱学。这些互补方法的应用有可能产生详细的心脏PP1相互作用组，这是确定新的和有针对性的药物干预的重要步骤。
Reversible phosphorylation of proteins is a delicate yet dynamic balancing act between kinases and phosphatases, the disturbance of which underlies numerous disease processes. While our understanding of protein kinases has grown tremendously over the past decades, relatively little is known regarding protein phosphatases. This may be because protein kinases are great in number and relatively specific in function, and thereby amenable to be studied in isolation, whereas protein phosphatases are much less abundant and more unspecific in their function. To achieve subcellular localization and substrate specificity, phosphatases depend on partnering with a large number of regulatory subunits, protein scaffolds and/or other interactors. This added layer of complexity presents a significant barrier to their study, but holds the key to unexplored opportunities for novel pharmacologic intervention. In this review we focus on the serine/threonine protein phosphatase type-1 (PP1), which plays an important role in cardiac physiology and pathophysiology. Although much work has been done to investigate the role of PP1 in cardiac diseases including atrial fibrillation and heart failure, most of these studies were limited to examining and manipulating the catalytic subunit(s) of PP1 without adequately considering the PP1 interactors, which give specificity to PP1’s functions. To complement these studies, three unbiased methods have been developed and applied to the mapping of the PP1 interactome: bioinformatics approaches, yeast two-hybrid screens, and affinity-purification mass spectrometry. The application of these complementary methods has the potential to generate a detailed cardiac PP1 interactome, which is an important step in identifying novel and targeted pharmacological interventions.
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影响因子：
3.3
作者：
Esteves, Sara L. C.;Domingues, Sara C.;da Cruz e Silva, Edgar F.
通讯作者：
da Cruz e Silva, Edgar F.
影响因子：
4.4
作者：
Hollin T;De Witte C;Lenne A;Pierrot C;Khalife J
通讯作者：
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影响因子：
10.8
作者：
El-Armouche, A;Pamminger, T;Eschenhagen, T
通讯作者：
Eschenhagen, T
DOI：
10.1152/ajpheart.00442.2003
发表时间：
2003-12-01
影响因子：
4.8
作者：
Gupta, RC;Mishra, S;Sabbah, HN
通讯作者：
Sabbah, HN
影响因子：
5
作者：
Greiser, Maura;Neuberger, Hans-Ruprecht;Schotten, Ulrich
通讯作者：
Schotten, Ulrich