Reconstruction of insulin signal flow from phosphoproteome and metabolome data

Katsuyuki Yugi, Hiroyuki Kubota, Yu Toyoshima, Rei Noguchi, Kentaro Kawata, Yasunori Komori, Shinsuke Uda, Katsuyuki Kunida, Yoko Tomizawa, Yosuke Funato, Hiroaki Miki, Masaki Matsumoto, Keiichi I. Nakayama, Kasumi Kashikura, Keiko Endo, Kazutaka Ikeda, Tomoyoshi Soga, Shinya Kuroda

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40 Citations (Scopus)

Abstract

Cellular homeostasis is regulated by signals through multiple molecular networks that include protein phosphorylation and metabolites. However, where and when the signal flows through a network and regulates homeostasis has not been explored. We have developed a reconstruction method for the signal flow based on time-course phosphoproteome and metabolome data, using multiple databases, and have applied it to acute action of insulin, an important hormone for metabolic homeostasis. An insulin signal flows through a network, through signaling pathways that involve 13 protein kinases, 26 phosphorylated metabolic enzymes, and 35 allosteric effectors, resulting in quantitative changes in 44 metabolites. Analysis of the network reveals that insulin induces phosphorylation and activation of liver-type phosphofructokinase 1, thereby controlling a key reaction in glycolysis. We thus provide a versatile method of reconstruction of signal flow through the network using phosphoproteome and metabolome data.

Original languageEnglish
Pages (from-to)1171-1183
Number of pages13
JournalCell Reports
Volume8
Issue number4
DOIs
Publication statusPublished - 2014 Aug 21

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Yugi, K., Kubota, H., Toyoshima, Y., Noguchi, R., Kawata, K., Komori, Y., Uda, S., Kunida, K., Tomizawa, Y., Funato, Y., Miki, H., Matsumoto, M., Nakayama, K. I., Kashikura, K., Endo, K., Ikeda, K., Soga, T., & Kuroda, S. (2014). Reconstruction of insulin signal flow from phosphoproteome and metabolome data. Cell Reports, 8(4), 1171-1183. https://doi.org/10.1016/j.celrep.2014.07.021