Dataset Information

Eungdamrong2007_Ras_Activation

ABSTRACT: The model reproduces the time profiles of Golgi Ras-GTP and plasma membrane Ras-GTP, subjected to a palmitoylation rate of 0.00015849 second inverse. This is depicted in Fig 5a and 5b for various palmitolylation rates, however the value used in this model is not present in the figure in the paper but corresponds to Fig S2 of the supplement. Model successfully reproduced using MathSBML. Please note that the units of volumetric species in this model are molecules/micrometer cubed, to convert this to microMolar as given in the paper, multiply the simulation result by 1/602. 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: Harish Dharuri

PROVIDER: BIOMD0000000161 | BioModels | 2008-01-29

REPOSITORIES: BioModels

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Publications

Compartment-specific feedback loop and regulated trafficking can result in sustained activation of Ras at the Golgi.

Eungdamrong Narat J NJ Iyengar Ravi R

Biophysical journal 20061110 3

Imaging experiments have shown that cell signaling components such as Ras can be activated by growth factors at distinct subcellular locations. Trafficking between these subcellular locations is a regulated dynamic process. The effects of trafficking and the molecular mechanisms underlying compartment-specific Ras activation were studied using numerical simulations of an ordinary differential equation-based multi-compartment model. The simulations show that interplay between two distinct mechani ...[more]

PMID: 17098795

Publication: 1/3

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Project description:Phillips2003 - The Mechanism of Ras GTPase Activation by Neurofibromin A mathematical model for Ras-GTP activation by neurofibromin and the kinetic rates of the relevant reactions. This model is described in the article: The mechanism of Ras GTPase activation by neurofibromin. Phillips RA, Hunter JL, Eccleston JF, Webb MR. Biochemistry 2003 Apr; 42(13): 3956-3965 Abstract: Individual rate constants have been determined for each step of the Ras.GTP hydrolysis mechanism, activated by neurofibromin. Fluorescence intensity and anisotropy stopped-flow measurements used the fluorescent GTP analogue, mantGTP (2'(3')-O-(N-methylanthraniloyl)GTP), to determine rate constants for binding and release of neurofibromin. Quenched flow measurements provided the kinetics of the hydrolytic cleavage step. The fluorescent phosphate sensor, MDCC-PBP was used to measure phosphate release kinetics. Phosphate-water oxygen exchange, using (18)O-substituted GTP and inorganic phosphate (P(i)), was used to determine the extent of reversal of the hydrolysis step and of P(i) binding. The data show that neurofibromin and P(i) dissociate from the NF1.Ras.GDP.P(i) complex with identical kinetics, which are 3-fold slower than the preceding cleavage step. A model is presented in which the P(i) release is associated with the change of Ras from "GTP" to "GDP" conformation. In this model, the conformation change on P(i) release causes the large change in affinity of neurofibromin, which then dissociates rapidly. This model is hosted on BioModels Database and identified by: BIOMD0000000692. To cite BioModels Database, please use: Chelliah V et al. BioModels: ten-year anniversary. Nucl. Acids Res. 2015, 43(Database issue):D542-8. 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

Eungdamrong2007_Ras_Activation

Publications

Compartment-specific feedback loop and regulated trafficking can result in sustained activation of Ras at the Golgi.

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