Prediction of cyclin-dependent kinase phosphorylation substrates.
Prediction of cyclin-dependent kinase phosphorylation substrates.
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DOI：
10.1371/journal.pone.0000656
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发表时间：
2007-08-01
期刊：
影响因子：
3.7
通讯作者：
Gaasterland, Terry
中科院分区：
文献类型：
--
作者：
Chang, Emmanuel J.;Begum, Rashida;Chait, Brian T.;Gaasterland, Terry
细胞周期蛋白依赖性激酶（Cdks）家族介导的蛋白质磷酸化在真核生物的细胞分裂周期中起着核心作用。Cdks的磷酸化作用通过改变关键过程（如DNA复制和有丝分裂过程）调节因子的功能来指导细胞周期。在这里，我们提出了一种新的计算程序来预测酿酒酵母中周期蛋白依赖性激酶Cdc28 （Cdk1）的底物。目前，大多数计算磷酸化位点预测程序仅关注局部序列特征。在本程序中，我们基于底物的局部和全局特征对Cdk底物进行建模。因此，我们定义了代表Cdc28磷酸化位点的局部序列基序，并随后模拟了这些基序在蛋白质序列中的聚类。这种限制反映了许多已知Cdk底物含有多个聚集磷酸化位点的观察结果。目前的策略定义了Cdk底物高度富集的蛋白质组的一个子集，通过将其与一组真实的、已发表的、实验表征的Cdk底物进行比较来验证，据我们所知，在撰写本文时，这些底物是全面的。为了证实我们的模型，我们将其预测与三个实验独立的Cdk蛋白质组学数据集进行了比较，发现了显著的重叠。最后，我们使用质谱法直接检测了选定的假定底物的Cdk基序的体内磷酸化。
Protein phosphorylation, mediated by a family of enzymes called cyclin-dependent kinases (Cdks), plays a central role in the cell-division cycle of eukaryotes. Phosphorylation by Cdks directs the cell cycle by modifying the function of regulators of key processes such as DNA replication and mitotic progression. Here, we present a novel computational procedure to predict substrates of the cyclin-dependent kinase Cdc28 (Cdk1) in the Saccharomyces cerevisiae. Currently, most computational phosphorylation site prediction procedures focus solely on local sequence characteristics. In the present procedure, we model Cdk substrates based on both local and global characteristics of the substrates. Thus, we define the local sequence motifs that represent the Cdc28 phosphorylation sites and subsequently model clustering of these motifs within the protein sequences. This restraint reflects the observation that many known Cdk substrates contain multiple clustered phosphorylation sites. The present strategy defines a subset of the proteome that is highly enriched for Cdk substrates, as validated by comparing it to a set of bona fide, published, experimentally characterized Cdk substrates which was to our knowledge, comprehensive at the time of writing. To corroborate our model, we compared its predictions with three experimentally independent Cdk proteomic datasets and found significant overlap. Finally, we directly detected in vivo phosphorylation at Cdk motifs for selected putative substrates using mass spectrometry.
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影响因子：
14.9
作者：
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通讯作者：
Sali, A
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