title: Construction and Deciphering of Human Phosphorylation-Mediated Signaling Transduction Networks.
abstract: Protein phosphorylation is the most abundant reversible covalent modification. Human protein kinases participate in almost all biological pathways, and approximately half of the kinases are associated with disease. PhoSigNet was designed to store and display human phosphorylation-mediated signal transduction networks, with additional information related to cancer. It contains 11 976 experimentally validated directed edges and 216 871 phosphorylation sites. Moreover, 3491 differentially expressed proteins in human cancer from dbDEPC, 18 907 human cancer variation sites from CanProVar, and 388 hyperphosphorylation sites from PhosphoSitePlus were collected as annotation information. Compared with other phosphorylation-related databases, PhoSigNet not only takes the kinase-substrate regulatory relationship pairs into account, but also extends regulatory relationships up- and downstream (e.g., from ligand to receptor, from G protein to kinase, and from transcription factor to targets). Furthermore, PhoSigNet allows the user to investigate the impact of phosphorylation modifications on cancer. By using one set of in-house time series phosphoproteomics data, the reconstruction of a conditional and dynamic phosphorylation-mediated signaling network was exemplified. We expect PhoSigNet to be a useful database and analysis platform benefiting both proteomics and cancer studies.
authors.affiliation: †Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.|‡Shanghai Center for Bioinformation Technology, Shanghai Academy of Science and Technology, Shanghai 201203, China.
authors.forename: Menghuan
authors.initials: M
authors.lastname: Zhang
authors.affiliation: ‡Shanghai Center for Bioinformation Technology, Shanghai Academy of Science and Technology, Shanghai 201203, China.|§Key Laboratory of Systems Biology, Shanghai Institutes for Biological Science, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: ‡Shanghai Center for Bioinformation Technology, Shanghai Academy of Science and Technology, Shanghai 201203, China.|§Key Laboratory of Systems Biology, Shanghai Institutes for Biological Science, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: He
authors.affiliation: ‡Shanghai Center for Bioinformation Technology, Shanghai Academy of Science and Technology, Shanghai 201203, China.|§Key Laboratory of Systems Biology, Shanghai Institutes for Biological Science, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Han
authors.initials: H
authors.lastname: Sun
authors.affiliation: ⊥Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai Jiao Tong University, Shanghai 200025, China.
authors.forename: Li
authors.initials: L
authors.lastname: Xia
authors.affiliation: ⊥Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai Jiao Tong University, Shanghai 200025, China.
authors.forename: Lishun
authors.initials: L
authors.lastname: Wang
authors.affiliation: †Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.|‡Shanghai Center for Bioinformation Technology, Shanghai Academy of Science and Technology, Shanghai 201203, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Sun
authors.affiliation: ‡Shanghai Center for Bioinformation Technology, Shanghai Academy of Science and Technology, Shanghai 201203, China.
authors.forename: Liangxiao
authors.initials: L
authors.lastname: Ma
authors.affiliation: ‡Shanghai Center for Bioinformation Technology, Shanghai Academy of Science and Technology, Shanghai 201203, China.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Zhang
authors.affiliation: †Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: †Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.|‡Shanghai Center for Bioinformation Technology, Shanghai Academy of Science and Technology, Shanghai 201203, China.|§Key Laboratory of Systems Biology, Shanghai Institutes for Biological Science, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Yixue
authors.initials: Y
authors.lastname: Li
authors.affiliation: ‡Shanghai Center for Bioinformation Technology, Shanghai Academy of Science and Technology, Shanghai 201203, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Xie
mesh_terms: D006801:Humans; D009369:Neoplasms / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D015398:Signal Transduction; D013379:Substrate Specificity
chemical_list: D011494:Protein Kinases
keywords: cancer; database; network; phosphorylation; signal transduction