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Molecular & Cellular Proteomics 7:1598-1608, 2008.
© 2008 by The American Society for Biochemistry and Molecular Biology, Inc.

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Research

GPS 2.0, a Tool to Predict Kinase-specific Phosphorylation Sites in Hierarchy ^*,S

Yu Xue^,, Jian Ren^,, Xinjiao Gao, Changjiang Jin, Longping Wen^,|| and Xuebiao Yao^,**,,¶

From the Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China and ^** Department of Physiology and Cancer Biology Program, Morehouse School of Medicine, Atlanta, Georgia 30310

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.

To whom correspondence may be addressed. Tel.: 86-551-3606304; Fax: 86-551-3607141; E-mail: yaoxb{at}ustc.edu.cn

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