Insulin induces phosphorylation and activation of liver-type phosphofructokinase 1, which thereby controls a key reaction in glycolysis. This mechanism is revealed using the mathematical model. In this model, the PFKL phosphorylation time courses are obtained from experimental data.
Author's Note: Katsuyuki Yugi thank Akira Funahashi (Keio University, Japan) for his kind advice in converting the model from MATLAB to SBML.
This model is described in the article:
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.
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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
- Cell reports , 8/ 2014 , Volume 8 , Issue 4 , pages: 1171-1183 , PubMed ID: 25131207
- Department of Biological Sciences, Graduate School of Science, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.
- 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.
Submitter of this revision: administrator
Curator: Lucian Smith
Modellers: administrator, Katsuyuki Yugi
Metadata information
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Model files (1) |
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BIOMD0000000540_url.xml | SBML L2V4 representation of Yugi2014 - Insulin induced signalling (PFKL phosphorylation) - model 1 | 93.44 KB | Preview | Download |
Additional files (11) |
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BIOMD0000000540-biopax2.owl | Auto-generated BioPAX (Level 2) | 20.37 KB | Preview | Download |
BIOMD0000000540-biopax3.owl | Auto-generated BioPAX (Level 3) | 30.47 KB | Preview | Download |
BIOMD0000000540.m | Auto-generated Octave file | 10.25 KB | Preview | Download |
BIOMD0000000540.pdf | Auto-generated PDF file | 213.60 KB | Preview | Download |
BIOMD0000000540.png | Auto-generated Reaction graph (PNG) | 153.38 KB | Preview | Download |
BIOMD0000000540.sci | Auto-generated Scilab file | 67.00 Bytes | Preview | Download |
BIOMD0000000540.svg | Auto-generated Reaction graph (SVG) | 31.78 KB | Preview | Download |
BIOMD0000000540.vcml | Auto-generated VCML file | 50.82 KB | Preview | Download |
BIOMD0000000540.xpp | Auto-generated XPP file | 7.13 KB | Preview | Download |
BIOMD0000000540_urn.xml | Auto-generated SBML file with URNs | 93.03 KB | Preview | Download |
PFKL_ins001.xml | The SBML model that was used to generate the blue plot (0.01 nM insulin concentration) in the curation figure. This file was provided by the author as an additional file. | 70.21 KB | Preview | Download |
- Model originally submitted by : Katsuyuki Yugi
- Submitted: Jun 13, 2014 3:01:29 AM
- Last Modified: Aug 21, 2024 10:54:07 PM
Revisions
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Version: 4
- Submitted on: Aug 21, 2024 10:54:07 PM
- Submitted by: Lucian Smith
- With comment: CRBM-sponsored manual and automated updates.
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Version: 3
- Submitted on: Dec 21, 2018 5:32:17 PM
- Submitted by: administrator
- With comment: Include the additional files provided by the submitter in the original submission: PFKL_ins001.xml
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Version: 2
- Submitted on: Sep 8, 2014 3:05:40 PM
- Submitted by: Katsuyuki Yugi
- With comment: Current version of Yugi2014 - Insulin induced signalling (PFKL phosphorylation) - model 1
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Version: 1
- Submitted on: Jun 13, 2014 3:01:29 AM
- Submitted by: Katsuyuki Yugi
- With comment: Original import of BIOMD0000000540.xml.origin
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(added: 14 Aug 2014, 13:50:34, updated: 14 Aug 2014, 13:50:34)