Molecular & Cellular Proteomics
Volume 7, Issue 9, September 2008, Pages 1598-1608
Journal home page for Molecular & Cellular Proteomics

Research
GPS 2.0, a Tool to Predict Kinase-specific Phosphorylation Sites in Hierarchy

https://doi.org/10.1074/mcp.M700574-MCP200Get rights and content
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Identification of protein phosphorylation sites with their cognate protein kinases (PKs) is a key step to delineate molecular dynamics and plasticity underlying a variety of cellular processes. Although nearly 10 kinase-specific prediction programs have been developed, numerous PKs have been casually classified into subgroups without a standard rule. For large scale predictions, the false positive rate has also never been addressed. In this work, we adopted a well established rule to classify PKs into a hierarchical structure with four levels, including group, family, subfamily, and single PK. In addition, we developed a simple approach to estimate the theoretically maximal false positive rates. The on-line service and local packages of the GPS (Group-based Prediction System) 2.0 were implemented in Java with the modified version of the Group-based Phosphorylation Scoring algorithm. As the first stand alone software for predicting phosphorylation, GPS 2.0 can predict kinase-specific phosphorylation sites for 408 human PKs in hierarchy. A large scale prediction of more than 13,000 mammalian phosphorylation sites by GPS 2.0 was exhibited with great performance and remarkable accuracy. Using Aurora-B as an example, we also conducted a proteome-wide search and provided systematic prediction of Aurora-B-specific substrates including protein-protein interaction information. Thus, the GPS 2.0 is a useful tool for predicting protein phosphorylation sites and their cognate kinases and is freely available on line.

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Published, MCP Papers in Press, May 6, 2008, DOI 10.1074/mcp.M700574-MCP200

This work was supported, in whole or in part, by National Institutes of Health Grant DK56292. This work was also supported by Chinese 973 Project Grants 2002CB713700, 2006CB943603, 2007CB914503, and 2006CB933300; Chinese Academy of Sciences Grants KSCX1-YW-R65, KSCX2-YW-21, and KJCX2-YW-M02; Chinese Natural Science Foundation Grants 39925018, 30270293, 90508002, and 30700138. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.mcponline.org) contains supplemental material.

§

Both authors contributed equally to this work.

A Georgia Cancer Coalition Eminent Scholar.