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首页> 外文期刊>Genomics >Proteome-wide prediction of PKA phosphorylation sites in eukaryotic kingdom.
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Proteome-wide prediction of PKA phosphorylation sites in eukaryotic kingdom.

机译：蛋白质组范围内真核生物中PKA磷酸化位点的预测。

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摘要

Protein phosphorylation is one of the most essential post-translational modifications (PTMs), and orchestrates a variety of cellular functions and processes. Besides experimental studies, numerous computational predictors implemented in various algorithms have been developed for phosphorylation sites prediction. However, large-scale predictions of kinase-specific phosphorylation sites have not been successfully pursued and remained to be a great challenge. In this work, we raised a "kiss farewell" model and conducted a high-throughput prediction of cAMP-dependent kinase (PKA) phosphorylation sites. Since a protein kinase (PK) should at least "kiss" its substrates and then run away, we proposed a PKA-binding protein to be a potential PKA substrate if at least one PKA site was predicted. To improve the prediction specificity, we reduced false positive rate (FPR) less than 1% when the cut-off value was set as 4. Successfully, we predicted 1387, 630, 568 and 912 potential PKA sites from 410, 217, 173 and 260 PKA-interacting proteins in Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster and Homo sapiens, respectively. Most of these potential phosphorylation sites remained to be experimentally verified. In addition, we detected two sites in one of PKA regulatory subunits to be conserved in eukaryotes as potentially ancient regulatory signals. Our prediction results provide an excellent resource for delineating PKA-mediated signaling pathways and their system integration underlying cellular dynamics and plasticity.
机译：蛋白质磷酸化是最重要的翻译后修饰（PTM）之一，并协调各种细胞功能和过程。除实验研究外，还开发了多种算法预测的计算预测因子用于磷酸化位点预测。但是，尚未成功地进行激酶特异性磷酸化位点的大规模预测，这仍然是一个巨大的挑战。在这项工作中，我们提出了“亲吻告别”模型，并进行了cAMP依赖性激酶（PKA）磷酸化位点的高通量预测。由于蛋白激酶（PK）至少应“亲吻”其底物然后逃逸，因此，如果预测到至少一个PKA位点，我们建议PKA结合蛋白是潜在的PKA底物。为了提高预测的特异性，当将临界值设置为4时，我们将假阳性率（FPR）降低了不到1％。成功地，我们从410、217、173和190位预测了1387、630、568和912个潜在的PKA位点。酿酒酵母，秀丽隐杆线虫，黑腹果蝇和智人中的260种PKA相互作用蛋白。这些潜在的磷酸化位点大多数仍需进行实验验证。此外，我们在真核生物中检测到一个PKA调控亚基中的两个位点，作为潜在的古老调控信号进行了保守。我们的预测结果为描述PKA介导的信号通路及其在细胞动力学和可塑性基础上的系统整合提供了极好的资源。

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