Elucidation of the evolutionary expansion of phosphorylation signaling networks using comparative phosphomotif analysis.

Elucidation of the evolutionary expansion of phosphorylation signaling networks using comparative phosphomotif analysis.
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DOI:
10.1186/1471-2164-15-546
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发表时间:
2014-07-01
期刊:
影响因子:
4.4
通讯作者:
Okuda S
Okuda S
中科院分区:
生物学2区
文献类型:
--
作者:
Yoshizaki H;Okuda S

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蛋白质磷酸化由激酶催化,并参与调节广泛的过程。蛋白质序列基序中的磷酸化位点决定了所涉及的激酶类型。磷酸化蛋白质组学的发展已经允许鉴定大量的磷酸化位点,其中一些不参与生理功能。我们开发了一种提取在细胞功能中具有重要作用的磷酸化位点的方法,并根据对34,366个磷酸化位点的分析确定了178个磷酸化位点。我们比较了丝氨酸/苏氨酸/酪氨酸残基在人类和其他七个物种中观察到的保守性。因此,我们确定了16个磷酸铁,物种之间的保护水平增加。在人和蠕虫中高度保守的磷酸化突变是激酶的调控位点。果蝇中存在的基序是新的磷酸化基序,包括参与基因表达调控的锌指基序。随后,我们发现这个锌指基序有助于亚细胞蛋白定位。在鱼类中识别的基序使我们能够检测到与选择性剪接相关的磷酸化信号的扩展。我们还表明,存在于特定物种中的基序在一个额外的网络中发挥作用,该网络直接与从酵母到人类的核心信号网络相互作用。我们的方法可能有助于有效地提取新的磷酸化的生理功能,从而大大有助于复杂的磷酸化信号级联反应的分析。我们的研究表明,在进化过程中获得的磷酸化网络增加了信号网络模块的核心信号网络。本文的在线版本(doi:10.1186/1471-2164-15-546)包含补充材料,可供授权用户使用。
Protein phosphorylation is catalyzed by kinases and is involved in the regulation of a wide range of processes. The phosphosites in protein sequence motifs determine the types of kinases involved. The development of phosphoproteomics has allowed the identification of huge numbers of phosphosites, some of which are not involved in physiological functions. We developed a method for extracting phosphosites with important roles in cellular functions and determined 178 phosphomotifs based on the analysis of 34,366 phosphosites. We compared the conservation of serine/threonine/tyrosine residues observed in humans and seven other species. Consequently, we identified 16 phosphomotifs, where the level of conservation increased among species. The highly conserved phosphomotifs in humans and the worm were kinase regulatory sites. The motifs present in the fly were novel phosphomotifs, including zinc finger motifs involved in the regulation of gene expression. Subsequently, we found that this zinc finger motif contributed to subcellular protein localization. The motifs identified in fish allowed us to detect the expansion of phosphorylation signals related to alternative splicing. We also showed that the motifs present in specific species functioned in an additional network that interacted directly with the core signaling network conserved from yeast to humans. Our method may facilitate the efficient extraction of novel phosphomotifs with physiological functions, thereby contributing greatly to the analysis of complex phosphorylation signaling cascades. Our study suggests that the phosphorylation networks acquired during evolution have added signaling network modules to the core signaling networks. The online version of this article (doi:10.1186/1471-2164-15-546) contains supplementary material, which is available to authorized users.
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