Dataset Information

Fisher2006_NFAT_Activation

ABSTRACT: The model reproduces the kinetics of the nuclear factor of activated cells (NFAT) as depicted in Figure 3a of the paper. Model was successfully tested on Jarnac and MathSBML 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: BIOMD0000000123 | BioModels | 2007-06-26

REPOSITORIES: BioModels

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Publications

NFAT and NFkappaB activation in T lymphocytes: a model of differential activation of gene expression.

Fisher Wayne G WG Yang Pei-Chi PC Medikonduri Ram K RK Jafri M Saleet MS

Annals of biomedical engineering 20061010 11

Mathematical models for the regulation of the Ca(2+)-dependent transcription factors NFAT and NFkappaB that are involved in the activation of the immune and inflammatory responses in T lymphocytes have been developed. These pathways are important targets for drugs, which act as powerful immunosuppressants by suppressing activation of NFAT and NFkappaB in T cells. The models simulate activation and deactivation over physiological concentrations of Ca(2+), diacyl glycerol (DAG), and PKCtheta using ...[more]

PMID: 17031595

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Project description:Tomida2003 - NFAT functions Calcium Oscillation This model is described in the article: NFAT functions as a working memory of Ca2+ signals in decoding Ca2+ oscillation. Tomida T, Hirose K, Takizawa A, Shibasaki F, Iino M. EMBO J. 2003 Aug; 22(15): 3825-3832 Abstract: Transcription by the nuclear factor of activated T cells (NFAT) is regulated by the frequency of Ca(2+) oscillation. However, why and how Ca(2+) oscillation regulates NFAT activity remain elusive. NFAT is dephosphorylated by Ca(2+)-dependent phosphatase calcineurin and translocates from the cytoplasm to the nucleus to initiate transcription. We analyzed the kinetics of dephosphorylation and translocation of NFAT. We show that Ca(2+)-dependent dephosphorylation proceeds rapidly, while the rephosphorylation and nuclear transport of NFAT proceed slowly. Therefore, after brief Ca(2+) stimulation, dephosphorylated NFAT has a lifetime of several minutes in the cytoplasm. Thus, Ca(2+) oscillation induces a build-up of dephosphorylated NFAT in the cytoplasm, allowing effective nuclear translocation, provided that the oscillation interval is shorter than the lifetime of dephosphorylated NFAT. We also show that Ca(2+) oscillation is more cost-effective in inducing the translocation of NFAT than continuous Ca(2+) signaling. Thus, the lifetime of dephosphorylated NFAT functions as a working memory of Ca(2+) signals and enables the control of NFAT nuclear translocation by the frequency of Ca(2+) oscillation at a reduced cost of Ca(2+) signaling. This model is hosted on BioModels Database and identified by: BIOMD0000000678. 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

Fisher2006_NFAT_Activation

Publications

NFAT and NFkappaB activation in T lymphocytes: a model of differential activation of gene expression.

Similar Datasets

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