Tomida2003 - Calcium Oscillatory-induced translocation of nuclear factor of activated T cells
This model is described in the article:
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.
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NFAT functions as a working memory of Ca2+ signals in decoding Ca2+ oscillation.
- Tomida T, Hirose K, Takizawa A, Shibasaki F, Iino M
- The EMBO journal , 8/ 2003 , Volume 22 , Issue 15 , pages: 3825-3832 , PubMed ID: 12881417
- Department of Pharmacology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
- 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.
Submitter of this revision: administrator
Modellers: administrator, Vijayalakshmi Chelliah
Metadata information
isDescribedBy (2 statements)
hasTaxon (1 statement)
isVersionOf (1 statement)
occursIn (1 statement)
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| Name | Description | Size | Actions |
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Model files |
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| BIOMD0000000678_url.xml | SBML L2V4 representation of Tomida2003 - Calcium Oscillatory-induced translocation of nuclear factor of activated T cells | 37.39 KB | Preview | Download |
Additional files |
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| BIOMD0000000678-biopax2.owl | Auto-generated BioPAX (Level 2) | 11.47 KB | Preview | Download |
| BIOMD0000000678-biopax3.owl | Auto-generated BioPAX (Level 3) | 15.67 KB | Preview | Download |
| BIOMD0000000678.m | Auto-generated Octave file | 4.74 KB | Preview | Download |
| BIOMD0000000678.pdf | Auto-generated PDF file | 155.20 KB | Preview | Download |
| BIOMD0000000678.png | Auto-generated Reaction graph (PNG) | 23.53 KB | Preview | Download |
| BIOMD0000000678.sci | Auto-generated Scilab file | 154.00 Bytes | Preview | Download |
| BIOMD0000000678.svg | Auto-generated Reaction graph (SVG) | 10.04 KB | Preview | Download |
| BIOMD0000000678.vcml | Auto-generated VCML file | 47.03 KB | Preview | Download |
| BIOMD0000000678.xpp | Auto-generated XPP file | 3.31 KB | Preview | Download |
| BIOMD0000000678_urn.xml | Auto-generated SBML file with URNs | 37.18 KB | Preview | Download |
| MODEL0912160005.cps | Curated and annotated COPASI file. | 46.77 KB | Preview | Download |
| MODEL0912160005.sedml | SED-ML file for figure 3C (high frequency) of the reference publication. | 2.22 KB | Preview | Download |
- Model originally submitted by : Vijayalakshmi Chelliah
- Submitted: Dec 16, 2009 4:55:41 PM
- Last Modified: Mar 14, 2018 9:35:37 AM
Revisions
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Version: 3
- Submitted on: Mar 14, 2018 9:35:37 AM
- Submitted by: administrator
- With comment: Current curated version of Tomida2003_NFATfunctions_CalciumOscillation
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Version: 2
- Submitted on: Jan 21, 2010 1:01:13 PM
- Submitted by: Vijayalakshmi Chelliah
- With comment: Current version of Tomida2003_NFATfunctions_CalciumOscillation
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Version: 1
- Submitted on: Dec 16, 2009 4:55:41 PM
- Submitted by: Vijayalakshmi Chelliah
- With comment: Original import of Tomida2003_NFATfunctions_CalciumOscillation
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: Variable used inside SBML models
| Species | Initial Concentration/Amount |
|---|---|
| NFAT phosphorylated NFAT protein ; Nuclear factor of activated T-cells, cytoplasmic 3 |
1.0 mmol |
| NFAT dephosphorylated NFAT protein ; Nuclear factor of activated T-cells, cytoplasmic 3 |
0.0 mmol |
| NFAT transported Nuclear factor of activated T-cells, cytoplasmic 3 ; nucleus ; NFAT protein |
0.0 mmol |
| stimulus Stimulus |
1.0 mmol |
| Reactions | Rate | Parameters |
|---|---|---|
| NFAT_transported => NFAT_phosphorylated | Jurkat_cell*k4*NFAT_transported | k4 = 0.035 |
| NFAT_phosphorylated => NFAT_dephosphorylated; stimulus | Jurkat_cell*k1*stimulus*NFAT_phosphorylated | k1 = 0.359 |
| NFAT_dephosphorylated => NFAT_phosphorylated | Jurkat_cell*k2*NFAT_dephosphorylated | k2 = 0.147 |
| NFAT_dephosphorylated => NFAT_transported | Jurkat_cell*k3*NFAT_dephosphorylated | k3 = 0.06 |
| NFAT_transported = (1-NFAT_phosphorylated)-NFAT_dephosphorylated | [] | [] |
| stimulus = piecewise(1, (time-floor(time/ModelValue_13)*ModelValue_13) < ModelValue_17, 0) | [] | ModelValue_17 = 1.0; ModelValue_13 = 3.0 |
(added: 22 Feb 2018, 17:18:27, updated: 22 Feb 2018, 17:18:27)