Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, 13092 Berlin, Germany.
Institute of Virology, Charité-Universitätsmedizin, 10117 Berlin, Germany.
J Proteome Res. 2022 Jun 3;21(6):1575-1587. doi: 10.1021/acs.jproteome.2c00198. Epub 2022 May 24.
Phosphoproteomics routinely quantifies changes in the levels of thousands of phosphorylation sites, but functional analysis of such data remains a major challenge. While databases like PhosphoSitePlus contain information about many phosphorylation sites, the vast majority of known sites is not assigned to any protein kinase. Assigning changes in the phosphoproteome to the activity of individual kinases therefore remains a key challenge. A recent large-scale study systematically identified in vitro substrates for most human protein kinases. Here, we reprocessed and filtered these data to generate an (iKiP-DB). We show that iKiP-DB can accurately predict changes in kinase activity in published phosphoproteomic data sets for both well-studied and poorly characterized kinases. We apply iKiP-DB to a newly generated phosphoproteomic analysis of SARS-CoV-2 infected human lung epithelial cells and provide evidence for coronavirus-induced changes in host cell kinase activity. In summary, we show that iKiP-DB is widely applicable to facilitate the functional analysis of phosphoproteomic data sets.
磷酸化蛋白质组学通常可定量检测数千个磷酸化位点水平的变化，但此类数据的功能分析仍然是一个主要挑战。虽然像 PhosphoSitePlus 这样的数据库包含了许多磷酸化位点的信息，但绝大多数已知的磷酸化位点都没有被分配给任何蛋白激酶。因此，将磷酸蛋白质组的变化分配给单个激酶的活性仍然是一个关键挑战。最近的一项大规模研究系统地鉴定了大多数人类蛋白激酶的体外底物。在这里，我们重新处理和过滤了这些数据，生成了一个 （iKiP-DB）。我们表明，iKiP-DB 可以准确预测已发表的磷酸蛋白质组数据集以及研究较好和研究较差的激酶的激酶活性变化。我们将 iKiP-DB 应用于新生成的 SARS-CoV-2 感染人肺上皮细胞的磷酸蛋白质组分析，并提供了冠状病毒引起宿主细胞激酶活性变化的证据。总之，我们表明，iKiP-DB 广泛适用于促进磷酸蛋白质组数据集的功能分析。
