期刊
CELL REPORTS
卷 8, 期 4, 页码 1171-1183出版社
CELL PRESS
DOI: 10.1016/j.celrep.2014.07.021
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资金
- Japan Science and Technology (JST)
- Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT) [21240025]
- Human Frontier Science Project (HFSP) grant [RGP0061/2011]
- MEXT [25117712, 22134007]
- JST
- Yamagata Prefectural Government
- City of Tsuruoka
- Grants-in-Aid for Scientific Research [26640080, 21240025, 22134007, 26120507, 25117712] Funding Source: KAKEN
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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