Reconstruction of Insulin Signal Flow from Phosphoproteome and Metabolome Data

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...

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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2014-08-01
Series:Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124714005907
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author 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
author_facet 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
author_sort Katsuyuki Yugi
collection DOAJ
description 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.
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spelling doaj.art-5aeb92b1cd164234a5216b8ad109b25a2022-12-21T20:01:12ZengElsevierCell Reports2211-12472014-08-01841171118310.1016/j.celrep.2014.07.021Reconstruction of Insulin Signal Flow from Phosphoproteome and Metabolome DataKatsuyuki Yugi0Hiroyuki Kubota1Yu Toyoshima2Rei Noguchi3Kentaro Kawata4Yasunori Komori5Shinsuke Uda6Katsuyuki Kunida7Yoko Tomizawa8Yosuke Funato9Hiroaki Miki10Masaki Matsumoto11Keiichi I. Nakayama12Kasumi Kashikura13Keiko Endo14Kazutaka Ikeda15Tomoyoshi Soga16Shinya Kuroda17Department of Biological Sciences, Graduate School of Science, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, JapanDepartment of Biological Sciences, Graduate School of Science, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, JapanDepartment of Biological Sciences, Graduate School of Science, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, JapanDepartment of Computational Biology, Graduate School of Frontier Sciences, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, JapanDepartment of Biological Sciences, Graduate School of Science, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, JapanDepartment of Biological Sciences, Graduate School of Science, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, JapanDepartment of Biological Sciences, Graduate School of Science, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, JapanDepartment of Biological Sciences, Graduate School of Science, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, JapanDepartment of Biological Sciences, Graduate School of Science, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, JapanDepartment of Cellular Regulation, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, JapanDepartment of Cellular Regulation, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, JapanDepartment of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka 812–8582, JapanDepartment of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka 812–8582, JapanInstitute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, JapanInstitute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, JapanInstitute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, JapanInstitute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, JapanDepartment of Biological Sciences, Graduate School of Science, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, JapanCellular 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.http://www.sciencedirect.com/science/article/pii/S2211124714005907
spellingShingle 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
Reconstruction of Insulin Signal Flow from Phosphoproteome and Metabolome Data
Cell Reports
title Reconstruction of Insulin Signal Flow from Phosphoproteome and Metabolome Data
title_full Reconstruction of Insulin Signal Flow from Phosphoproteome and Metabolome Data
title_fullStr Reconstruction of Insulin Signal Flow from Phosphoproteome and Metabolome Data
title_full_unstemmed Reconstruction of Insulin Signal Flow from Phosphoproteome and Metabolome Data
title_short Reconstruction of Insulin Signal Flow from Phosphoproteome and Metabolome Data
title_sort reconstruction of insulin signal flow from phosphoproteome and metabolome data
url http://www.sciencedirect.com/science/article/pii/S2211124714005907
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