Dataset Information

Wang2009 - PI3K Ras Crosstalk

ABSTRACT: This model is from the article: PI3K-dependent cross-talk interactions converge with Ras as quantifiable inputs integrated by Erk. Wang CC, Cirit M, Haugh JM Mol. Syst. Biol. 2009;5:246. 19225459 , Abstract: Although it is appreciated that canonical signal-transduction pathways represent dominant modes of regulation embedded in larger interaction networks, relatively little has been done to quantify pathway cross-talk in such networks. Through quantitative measurements that systematically canvas an array of stimulation and molecular perturbation conditions, together with computational modeling and analysis, we have elucidated cross-talk mechanisms in the platelet-derived growth factor (PDGF) receptor signaling network, in which phosphoinositide 3-kinase (PI3K) and Ras/extracellular signal-regulated kinase (Erk) pathways are prominently activated. We show that, while PI3K signaling is insulated from cross-talk, PI3K enhances Erk activation at points both upstream and downstream of Ras. The magnitudes of these effects depend strongly on the stimulation conditions, subject to saturation effects in the respective pathways and negative feedback loops. Motivated by those dynamics, a kinetic model of the network was formulated and used to precisely quantify the relative contributions of PI3K-dependent and -independent modes of Ras/Erk activation. This model is parameterized with the median of the estimated parameters given in the supplementary material of the original publication's (doi: 10.1038/msb.2009.4 ) supplement on pages 8 and 9. This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2010 The BioModels.net Team. 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. In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not.. 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: Lukas Endler

PROVIDER: BIOMD0000000288 | BioModels | 2024-09-02

REPOSITORIES: BioModels

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			Action	DRS
	BIOMD0000000288?filename=BIOMD0000000288-biopax2.owl	Owl
	BIOMD0000000288?filename=BIOMD0000000288-biopax3.owl	Owl
	BIOMD0000000288?filename=BIOMD0000000288-matlab.m	Other
	BIOMD0000000288?filename=BIOMD0000000288-octave.m	Other
	BIOMD0000000288?filename=BIOMD0000000288.m	Other

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PI3K-dependent cross-talk interactions converge with Ras as quantifiable inputs integrated by Erk.

Wang Chun-Chao CC Cirit Murat M Haugh Jason M JM

Molecular systems biology 20090217

Although it is appreciated that canonical signal-transduction pathways represent dominant modes of regulation embedded in larger interaction networks, relatively little has been done to quantify pathway cross-talk in such networks. Through quantitative measurements that systematically canvas an array of stimulation and molecular perturbation conditions, together with computational modeling and analysis, we have elucidated cross-talk mechanisms in the platelet-derived growth factor (PDGF) recepto ...[more]

PMID: 19225459

Publication: 1/3

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