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激酶信号转导的进化、动态和失调。

Evolution, dynamics and dysregulation of kinase signalling.

机构信息

European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Cambridge CB10 1SD, UK.

European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Cambridge CB10 1SD, UK.

出版信息

Curr Opin Struct Biol. 2018 Feb;48:133-140. doi: 10.1016/j.sbi.2017.12.008. Epub 2018 Jan 6.

Abstract

Protein kinases are central regulators of most eukaryotic cellular processes. While kinase signalling has been studied for decades, only through recent advances in mass spectrometry have we been able to identify phophosites in large scale and quantify their regulation across conditions. These advances are challenging our understanding of kinase signalling and shedding light into how these systems have evolved. Kinase substrate specificity appears to be strongly conserved but their target phosphosites diverge at a very fast rate. However, less is known about the functional consequences of such changes and the fraction of phosphosites that are crucial for organismal fitness. A better understanding of these evolutionary processes will facilitate the study of disease related genomic alterations that target these signalling circuits.

摘要

蛋白激酶是大多数真核细胞过程的核心调节剂。虽然激酶信号已经研究了几十年,但只有通过近年来质谱技术的进步,我们才能够大规模地鉴定磷酸化位点,并在不同条件下对其调控进行定量分析。这些进展正在挑战我们对激酶信号的理解,并揭示了这些系统是如何进化的。激酶底物特异性似乎是高度保守的,但它们的靶标磷酸化位点的变化速度非常快。然而,对于这些变化的功能后果以及对生物体适应性至关重要的磷酸化位点的比例,我们知之甚少。更好地了解这些进化过程将有助于研究针对这些信号通路的与疾病相关的基因组改变。

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