@article{c89818e76fb948c98e36013c0179821e,
title = "Reconstruction of global regulatory network from signaling to cellular functions using phosphoproteomic data",
abstract = "Cellular signaling regulates various cellular functions via protein phosphorylation. Phosphoproteomic data potentially include information for a global regulatory network from signaling to cellular functions, but a procedure to reconstruct this network using such data has yet to be established. In this paper, we provide a procedure to reconstruct a global regulatory network from signaling to cellular functions from phosphoproteomic data by integrating prior knowledge of cellular functions and inference of the kinase–substrate relationships (KSRs). We used phosphoproteomic data from insulin-stimulated Fao hepatoma cells and identified protein phosphorylation regulated by insulin specifically over-represented in cellular functions in the KEGG database. We inferred kinases for protein phosphorylation by KSRs, and connected the kinases in the insulin signaling layer to the phosphorylated proteins in the cellular functions, revealing that the insulin signal is selectively transmitted via the Pi3k-Akt and Erk signaling pathways to cellular adhesions and RNA maturation, respectively. Thus, we provide a method to reconstruct global regulatory network from signaling to cellular functions based on phosphoproteomic data.",
author = "Kentaro Kawata and Katsuyuki Yugi and Atsushi Hatano and Toshiya Kokaji and Yoko Tomizawa and Masashi Fujii and Shinsuke Uda and Hiroyuki Kubota and Masaki Matsumoto and Nakayama, {Keiichi I.} and Shinya Kuroda",
note = "Funding Information: Japan Science and Technology Corporation, Grant/Award Number: JPMJPR1538; Grant‐in‐Aid for Scientific Research on Innovative Areas, Grant/Award Number: 18H04801; Core Research for Evolutional Science and Technology, Grant/Award Number: JPMJCR12W3; Japan Society for the Promotion of Science, Grant/Award Number: 16K12508, 16H06577, 17H06299, 17H06300, 17H06301, 17H06306, 18H03979, JP15H05582 and JP18H05431; National Institute of Genetics (NIG); Research Organization of Information and Systems (ROIS) Funding Information: We thank our laboratory members for critically reading this manuscript and for their technical assistance with the experiments. The computational analysis of this work was performed in part with support of the supercomputer system of National Institute of Genetics (NIG) and Research Organization of Information and Systems (ROIS). This manuscript was edited by Nancy R. Gough (BioSerendipity, LLC). This work was supported by the Creation of Fundamental Technologies for Understanding and Control of Biosystem Dynamics, CREST (JPMJCR12W3), from the Japan Science and Technology Agency (JST); by the Japan Society for the Promotion of Science (JSPS) KAKENHI Grant Numbers (17H06300, 17H06299 and 18H03979). K.Y. receives funding from JSPS KAKENHI Grant Numbers JP15H05582 and JP18H05431, and “Creation of Innovative Technology for Medical Applications Based on the Global Analyses and Regulation of Disease‐Related Metabolites,” PRESTO (JPMJPR1538), from JST. M.F. was supported by JSPS KAKENHI Grant Number 16K12508. H.K. was supported by JSPS KAKENHI Grant Number 16H06577. S.U. receives funding from a Grant‐in‐Aid for Scientific Research on Innovative Areas (18H04801). K.I.N. was supported by the JSPS KAKENHI Grant Numbers (17H06301 and 17H06306). Funding Information: We thank our laboratory members for critically reading this manuscript and for their technical assistance with the experiments. The computational analysis of this work was performed in part with support of the supercomputer system of National Institute of Genetics (NIG) and Research Organization of Information and Systems (ROIS). This manuscript was edited by Nancy R. Gough (BioSerendipity, LLC). This work was supported by the Creation of Fundamental Technologies for Understanding and Control of Biosystem Dynamics, CREST (JPMJCR12W3), from the Japan Science and Technology Agency (JST); by the Japan Society for the Promotion of Science (JSPS) KAKENHI Grant Numbers (17H06300, 17H06299 and 18H03979). K.Y. receives funding from JSPS KAKENHI Grant Numbers JP15H05582 and JP18H05431, and ?Creation of Innovative Technology for Medical Applications Based on the Global Analyses and Regulation of Disease-Related Metabolites,? PRESTO (JPMJPR1538), from JST. M.F. was supported by JSPS KAKENHI Grant Number 16K12508. H.K. was supported by JSPS KAKENHI Grant Number 16H06577. S.U. receives funding from a Grant-in-Aid for Scientific Research on Innovative Areas (18H04801). K.I.N. was supported by the JSPS KAKENHI Grant Numbers (17H06301 and 17H06306). Publisher Copyright: {\textcopyright} 2018 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd",
year = "2019",
month = jan,
doi = "10.1111/gtc.12655",
language = "English",
volume = "24",
pages = "82--93",
journal = "Genes to Cells",
issn = "1356-9597",
publisher = "Wiley-Blackwell",
number = "1",
}