TY - JOUR
T1 - Reconstruction of insulin signal flow from phosphoproteome and metabolome data
AU - Yugi, Katsuyuki
AU - Kubota, Hiroyuki
AU - Toyoshima, Yu
AU - Noguchi, Rei
AU - Kawata, Kentaro
AU - Komori, Yasunori
AU - Uda, Shinsuke
AU - Kunida, Katsuyuki
AU - Tomizawa, Yoko
AU - Funato, Yosuke
AU - Miki, Hiroaki
AU - Matsumoto, Masaki
AU - Nakayama, Keiichi I.
AU - Kashikura, Kasumi
AU - Endo, Keiko
AU - Ikeda, Kazutaka
AU - Soga, Tomoyoshi
AU - Kuroda, Shinya
N1 - Funding Information:
We deeply thank Christian Klukas and Hendrik Rohn (Leibniz Institute of Plant Genetics and Crop Plant Research) for technical advices regarding visualization of the biological network using their VANTED software. The computational analysis of this work was performed in part with support of the super computer system of National Institute of Genetics (NIG), Research Organization of Information and Systems (ROIS). We thank Takashi Ito (Department of Biochemistry, Kyushu University Graduate School of Medical Sciences) for critically reading this manuscript and for helpful comments. We thank our laboratory members for critically reading this manuscript and for their technical assistance with the experiments. This work was supported by the Creation of Fundamental Technologies for Understanding and Control of Biosystem Dynamics, CREST, from the Japan Science and Technology (JST) , by a Kakenhi Scientific Research grant (A) (# 21240025 ) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT) ; and by a Human Frontier Science Project (HFSP) grant ( RGP0061/2011 ). This work was performed in part in the Cooperative Research Project Program of the Medical Institute of Bioregulation, Kyushu University. H.K. (Kubota) receives funding from a Grant-in-Aid for Scientific Research on Innovative Areas (# 25117712 ) from MEXT , and Elucidation and regulation in the dynamic maintenance and transfiguration of homeostasis in living body, PRESTO, from JST . T.S. (Soga) receives funding from a Grant-in-Aid for Scientific Research on Innovative Areas KAKENHI (# 22134007 ) from MEXT , and Creation of Innovative Technology for Medical Applications Based on the Global Analyses and Regulation of Disease-Related Metabolites, CREST, from JST , and the Yamagata Prefectural Government and City of Tsuruoka .
PY - 2014/8/21
Y1 - 2014/8/21
N2 - 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.
AB - 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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U2 - 10.1016/j.celrep.2014.07.021
DO - 10.1016/j.celrep.2014.07.021
M3 - Article
C2 - 25131207
AN - SCOPUS:84908356647
SN - 2211-1247
VL - 8
SP - 1171
EP - 1183
JO - Cell Reports
JF - Cell Reports
IS - 4
ER -