Dataset Information

Kholodenko1999 - EGFR signaling

ABSTRACT: Kholodenko1999 - EGFR signaling This model has been generated by the JWS Online project by Jacky Snoep using PySCeS Run this model online at http://jjj.biochem.sun.ac.za To cite JWS Online please refer to: Olivier, B.G. and Snoep, J.L. (2004) Web-based modelling using JWS Online , Bioinformatics, 20:2143-2144 This model is described in the article: Quantification of short term signaling by the epidermal growth factor receptor. Kholodenko BN, Demin OV, Moehren G, Hoek JB J. Biol. Chem. 1999 Oct; 274(42): 30169-30181 Abstract: During the past decade, our knowledge of molecular mechanisms involved in growth factor signaling has proliferated almost explosively. However, the kinetics and control of information transfer through signaling networks remain poorly understood. This paper combines experimental kinetic analysis and computational modeling of the short term pattern of cellular responses to epidermal growth factor (EGF) in isolated hepatocytes. The experimental data show transient tyrosine phosphorylation of the EGF receptor (EGFR) and transient or sustained response patterns in multiple signaling proteins targeted by EGFR. Transient responses exhibit pronounced maxima, reached within 15-30 s of EGF stimulation and followed by a decline to relatively low (quasi-steady-state) levels. In contrast to earlier suggestions, we demonstrate that the experimentally observed transients can be accounted for without requiring receptor-mediated activation of specific tyrosine phosphatases, following EGF stimulation. The kinetic model predicts how the cellular response is controlled by the relative levels and activity states of signaling proteins and under what conditions activation patterns are transient or sustained. EGFR signaling patterns appear to be robust with respect to variations in many elemental rate constants within the range of experimentally measured values. On the other hand, we specify which changes in the kinetic scheme, rate constants, and total amounts of molecular factors involved are incompatible with the experimentally observed kinetics of signal transfer. Quantitation of signaling network responses to growth factors allows us to assess how cells process information controlling their growth and differentiation. The model correctly reproduces all the figures from the paper. The curation has been done using SBMLodeSolver. This model is hosted on BioModels Database and identified by: BIOMD0000000048 . 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.

SUBMITTER: Lu Li

PROVIDER: BIOMD0000000048 | BioModels | 2005-11-23

REPOSITORIES: BioModels

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Publications

Quantification of short term signaling by the epidermal growth factor receptor.

Kholodenko B N BN Demin O V OV Moehren G G Hoek J B JB

The Journal of biological chemistry 19991001 42

During the past decade, our knowledge of molecular mechanisms involved in growth factor signaling has proliferated almost explosively. However, the kinetics and control of information transfer through signaling networks remain poorly understood. This paper combines experimental kinetic analysis and computational modeling of the short term pattern of cellular responses to epidermal growth factor (EGF) in isolated hepatocytes. The experimental data show transient tyrosine phosphorylation of the EG ...[more]

PMID: 10514507

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Project description:Sivakumar2011 - EGF Receptor Signaling Pathway EGFR belongs to the human epidermal receptor (HER) family of receptor tyrosine kinases, which consists of four closely related receptors (EGFR (HER1, erbB1), HER2 (neu, erbB2), HER3 (erbB3), and HER4 (erbB4)) that mediate cellular signaling pathways involved in growth and proliferation in response to the binding of a variety of growth factor ligands. There are currently six known endogenous ligands for EGFR: EGF, transforming growth factor- (TGF-), amphiregulin, betacellulin, heparin-binding EGF (HB-EGF), and epiregulin.Upon ligand binding, the EGFR forms homo- or heterodimeric complexes (usually with HER2), which leads to activation of the receptor tyrosine kinase, via autophosphorylation. References: The EGF receptor family--multiple roles in proliferation, differentiation, and neoplasia with an emphasis on HER4. An open-and-shut case? Recent insights into the activation of EGF/ErbB receptors. EGF receptor signaling: putting a new spin on eye development. Epidermal growth factor receptor: a promising target in solid tumours. This model is described in the article: A systems biology approach to model neural stem cell regulation by notch, shh, wnt, and EGF signaling pathways. Sivakumar KC, Dhanesh SB, Shobana S, James J, Mundayoor S. Omics: a Journal of Integrative Biology. 2011; 15(10):729-737 Abstract: The Notch, Sonic Hedgehog (Shh), Wnt, and EGF pathways have long been known to influence cell fate specification in the developing nervous system. Here we attempted to evaluate the contemporary knowledge about neural stem cell differentiation promoted by various drug-based regulations through a systems biology approach. Our model showed the phenomenon of DAPT-mediated antagonism of Enhancer of split [E(spl)] genes and enhancement of Shh target genes by a SAG agonist that were effectively demonstrated computationally and were consistent with experimental studies. However, in the case of model simulation of Wnt and EGF pathways, the model network did not supply any concurrent results with experimental data despite the fact that drugs were added at the appropriate positions. This paves insight into the potential of crosstalks between pathways considered in our study. Therefore, we manually developed a map of signaling crosstalk, which included the species connected by representatives from Notch, Shh, Wnt, and EGF pathways and highlighted the regulation of a single target gene, Hes-1, based on drug-induced simulations. These simulations provided results that matched with experimental studies. Therefore, these signaling crosstalk models complement as a tool toward the discovery of novel regulatory processes involved in neural stem cell maintenance, proliferation, and differentiation during mammalian central nervous system development. To our knowledge, this is the first report of a simple crosstalk map that highlights the differential regulation of neural stem cell differentiation and underscores the flow of positive and negative regulatory signals modulated by drugs. This model is hosted on BioModels Database and identified by: BIOMD0000000394. 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.

Dataset Information

Kholodenko1999 - EGFR signaling

Publications

Quantification of short term signaling by the epidermal growth factor receptor.

Similar Datasets

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