Dataset Information

Yugi2014 - Insulin induced signalling (PFKL phosphorylation) - model 2

ABSTRACT: Yugi2014 - Insulin induced signalling (PFKL phosphorylation) - model 2 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 calculation from the signalling pathway model developed by Kubata et al. (2012) ( MODEL1204060000 - Kubota2012_InsulinAction_AKTpathway). 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: Reconstruction of insulin signal flow from phosphoproteome and metabolome data. 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 KI, Kashikura K, Endo K, Ikeda K, Soga T, Kuroda S. Cell Rep 2014 Aug; 8(4): 1171-1183 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. This model is hosted on BioModels Database and identified by: BIOMD0000000541. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

OTHER RELATED OMICS DATASETS IN: PRJNA251959

SUBMITTER: Katsuyuki Yugi

PROVIDER: BIOMD0000000541 | BioModels | 2014-08-14

REPOSITORIES: BioModels

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Publications

Reconstruction of insulin signal flow from phosphoproteome and metabolome data.

Yugi Katsuyuki K Kubota Hiroyuki H Toyoshima Yu Y Noguchi Rei R Kawata Kentaro K Komori Yasunori Y Uda Shinsuke S Kunida Katsuyuki K Tomizawa Yoko Y Funato Yosuke Y Miki Hiroaki H Matsumoto Masaki M Nakayama Keiichi I KI Kashikura Kasumi K Endo Keiko K Ikeda Kazutaka K Soga Tomoyoshi T Kuroda Shinya S

Cell reports 20140814 4

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 sign ...[more]

PMID: 25131207

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Project description:Yugi2014 - Insulin induced signalling (PFKL phosphorylation) - model 1 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: Reconstruction of insulin signal flow from phosphoproteome and metabolome data. 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 KI, Kashikura K, Endo K, Ikeda K, Soga T, Kuroda S. Cell Rep 2014 Aug; 8(4): 1171-1183 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. This model is hosted on BioModels Database and identified by: BIOMD0000000540. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Project description:Neisseria meningitidis serogroup B is a pathogen that can infect diverse sites within the human host. According to the N. meningitidis genomic information and experimental observations glucose can be completely catabolized through the Entner-Doudoroff pathway and the pentose phosphate pathway. The Embden-Meyerhof-Parnas pathway is not functional, because the gene for phosphofructokinase is not present. The phylogenetic distribution of phosphofructokinase indicates that in most obligate aerobic organisms PFK is lacking. We conclude that this is because of the limited contribution of PFK to the energy supply in aerobically grown organisms in comparison with the energy generated through oxidative phosphorylation. Under anaerobic or microaerobic conditions the available energy is limiting and PFK provides an advantage, which explains the presence of PFK in many (facultative) anaerobic organisms. In accordance with this, in silico flux balance analysis predicted an increase of biomass yield as a result of PFK expression. However, analysis of a genetically engineered N. meningitidis strain that expresses a heterologous phosphofructokinase showed that the yield of biomass on substrate decreased in comparison with a pfkA deficient control strain, which was associated mainly with an increase in CO2 production, whereas production of by-products was comparable between the two strains. This might explain why the pfkA gene has not been obtained by horizontal gene transfer, since it is initially unfavourable for biomass yield. No large effects related to heterologous expression of pfkA were observed in the transcriptome. Although our results suggest that introduction of PFK does not contribute to a more efficient strain in terms of biomass yield, achievement of a robust, optimal metabolic network that enables a higher growth rate or a higher biomass yield, might be possible after adaptive evolution of the strain, which remains to be investigated. Two-condition experiment, 3 replicates per condition

Dataset Information

Yugi2014 - Insulin induced signalling (PFKL phosphorylation) - model 2

Publications

Reconstruction of insulin signal flow from phosphoproteome and metabolome data.

Similar Datasets

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