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

研究成果: Article

40 引用 (Scopus)

抜粋

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.

元の言語English
ページ(範囲)1171-1183
ページ数13
ジャーナルCell Reports
8
発行部数4
DOI
出版物ステータスPublished - 2014 8 21

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

これを引用

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