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ABSTRACT: This a model from the article: Prediction and validation of the distinct dynamics of transient and sustained ERK activation. Sasagawa S, Ozaki Y, Fujita K, Kuroda S Nat. Cell Biol.[2005 Apr; Volume: 7 (Issue: 4 )]: 365-73 15793571, Abstract: To elucidate the hidden dynamics of extracellular-signal-regulated kinase (ERK) signalling networks, we developed a simulation model of ERK signalling networks by constraining in silico dynamics based on in vivo dynamics in PC12 cells. We predicted and validated that transient ERK activation depends on rapid increases of epidermal growth factor and nerve growth factor (NGF) but not on their final concentrations, whereas sustained ERK activation depends on the final concentration of NGF but not on the temporal rate of increase. These ERK dynamics depend on Ras and Rap1 dynamics, the inactivation processes of which are growth-factor-dependent and -independent, respectively. Therefore, the Ras and Rap1 systems capture the temporal rate and concentration of growth factors, and encode these distinct physical properties into transient and sustained ERK activation, respectively. Dynamics of active Ras, active Rap1 and phosphorylated ERK were correctly reproduced with CellDesigner 3.0 This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2012 The BioModels.net Team. For more information see the terms of use. To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

SUBMITTER: Shinya Kuroda  

PROVIDER: BIOMD0000000049 | BioModels | 2005-12-21


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Autocrine loops with positive feedback enable context-dependent cell signaling.

Shvartsman S Y SY   Hagan M P MP   Yacoub A A   Dent P P   Wiley H S HS   Lauffenburger D A DA  

American journal of physiology. Cell physiology 20020301 3

We describe a mechanism for context-dependent cell signaling mediated by autocrine loops with positive feedback. We demonstrate that the composition of the extracellular medium can critically influence the intracellular signaling dynamics induced by extracellular stimuli. Specifically, in the epidermal growth factor receptor (EGFR) system, amplitude and duration of mitogen-activated protein kinase (MAPK) activation are modulated by the positive-feedback loop formed by the EGFR, the Ras-MAPK sign  ...[more]

Publication: 1/4

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