Maeda2006_MyosinPhosphorylation
The model reproduces Fig 2B, D, F, and 2H. The dynamics correspond to a stimulus of 1 U/ml of thrombin which is equal to 0.01 uM. Phosphorylated MLC is the sum of pMLC (s359) and ppMLC (s360). A slight discrepancy in peak values of species between the figure in the paper and simulation result might be due to different initial conditions in the two sets. The model was successfully tested on MathSBML. It is possible to simulate the model on other software that do not support "Events" at this time by removing the "listOfEvents" and substituting a value of 0.01 for thrombin (s2). This does not change the model very much. With the latter format, the model was also successfully tested on Copasi.
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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.
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Ca2+ -independent phospholipase A2-dependent sustained Rho-kinase activation exhibits all-or-none response.
- Maeda A, Ozaki Y, Sivakumaran S, Akiyama T, Urakubo H, Usami A, Sato M, Kaibuchi K, Kuroda S
- Genes to cells : devoted to molecular & cellular mechanisms , 9/ 2006 , Volume 11 , pages: 1071-1083 , PubMed ID: 16923126
- Undergraduate Program for Bioinformatics and Systems Biology, Graduate School of Information Science and Technology, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
- Sustained contraction of cells depends on sustained Rho-associated kinase (Rho-kinase) activation. We developed a computational model of the Rho-kinase pathway to understand the systems characteristics. Thrombin-dependent in vivo transient responses of Rho activation and Ca2+ increase could be reproduced in silico. Low and high thrombin stimulation induced transient and sustained phosphorylation, respectively, of myosin light chain (MLC) and myosin phosphatase targeting subunit 1 (MYPT1) in vivo. The transient phosphorylation of MLC and MYPT1 could be reproduced in silico, but their sustained phosphorylation could not. This discrepancy between in vivo and in silico in the sustained responses downstream of Rho-kinase indicates that a missing pathway(s) may be responsible for the sustained Rho-kinase activation. We found, experimentally, that the sustained phosphorylation of MLC and MYPT1 exhibit all-or-none responses. Bromoenol lactone, a specific inhibitor of Ca2+ -independent phospholipase A2 (iPLA2), inhibited sustained phosphorylation of MLC and MYPT1, which indicates that sustained Rho-kinase activation requires iPLA2 activity. Thus, the systems analysis of the Rho-kinase pathway identified a novel iPLA2-dependent mechanism of the sustained Rho-kinase activation, which exhibits an all-or-none response.
Metadata information
BioModels Database BIOMD0000000088
Gene Ontology regulation of Rho protein signal transduction
Gene Ontology actin cytoskeleton organization
| Name | Description | Size | Actions |
|---|---|---|---|
Model files |
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| BIOMD0000000088_url.xml | SBML L2V1 representation of Maeda2006_MyosinPhosphorylation | 241.65 KB | Preview | Download |
Additional files |
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| BIOMD0000000088.xpp | Auto-generated XPP file | 38.43 KB | Preview | Download |
| BIOMD0000000088-biopax3.owl | Auto-generated BioPAX (Level 3) | 329.43 KB | Preview | Download |
| BIOMD0000000088.m | Auto-generated Octave file | 50.63 KB | Preview | Download |
| BIOMD0000000088.png | Auto-generated Reaction graph (PNG) | 1.98 MB | Preview | Download |
| BIOMD0000000088_urn.xml | Auto-generated SBML file with URNs | 233.62 KB | Preview | Download |
| BIOMD0000000088.sci | Auto-generated Scilab file | 67.00 Bytes | Preview | Download |
| BIOMD0000000088-biopax2.owl | Auto-generated BioPAX (Level 2) | 200.41 KB | Preview | Download |
| BIOMD0000000088.pdf | Auto-generated PDF file | 721.11 KB | Preview | Download |
| BIOMD0000000088.svg | Auto-generated Reaction graph (SVG) | 274.02 KB | Preview | Download |
| BIOMD0000000088.vcml | Auto-generated VCML file | 322.23 KB | Preview | Download |
- Model originally submitted by : Yu-ichi Ozaki
- Submitted: 28-Jan-2007 23:57:52
- Last Modified: 08-Apr-2016 16:36:16
Revisions
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Version: 2
- Submitted on: 08-Apr-2016 16:36:16
- Submitted by: Yu-ichi Ozaki
- With comment: Current version of Maeda2006_MyosinPhosphorylation
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Version: 1
- Submitted on: 28-Jan-2007 23:57:52
- Submitted by: Yu-ichi Ozaki
- With comment: Original import of BIOMD0000000088.xml.origin
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: Variable used inside SBML models
| Species | Initial Concentration/Amount |
|---|---|
| s314 Protein kinase C alpha type |
0.68193 ÎĽmol |
| s324 Protein kinase C alpha type |
0.0 ÎĽmol |
| s330 | 0.0 ÎĽmol |
| s331 | 0.0 ÎĽmol |
| s335 Protein phosphatase 1 regulatory subunit 14A ; Protein kinase C alpha type |
0.0 ÎĽmol |
| s355 Protein phosphatase 1 regulatory subunit 12A ; Protein phosphatase 1 regulatory subunit 14A |
0.0 ÎĽmol |
| s293 calcium(2+) ; Calmodulin-3Calmodulin-1Calmodulin-2 ; Myosin light chain kinase 2, skeletal/cardiac muscle ; Calmodulin ; Calcium cation |
0.0 ÎĽmol |
| s294 calcium(2+) ; Calmodulin-3Calmodulin-1Calmodulin-2 ; Myosin light chain kinase 2, skeletal/cardiac muscle ; Calmodulin ; Calcium cation |
0.0 ÎĽmol |
| s295 calcium(2+) ; Calmodulin-3Calmodulin-1Calmodulin-2 ; Myosin light chain kinase 2, skeletal/cardiac muscle ; Calmodulin ; Calcium cation |
0.0 ÎĽmol |
| Reactions | Rate | Parameters |
|---|---|---|
| s314 => s330 | c1*kf*s314 | kf=4.63E-5 per_sec |
| s314 + s349 => s335 | c1*((1+ratio)*Vmax*s314*s349/Km-ratio*Vmax*s335) | Vmax=3.94 per_sec; Km=0.0014 microMolar; ratio=4.0 dimensionless |
| s335 => s314 + s350 | c1*Vmax*s335 | Vmax=3.94 per_sec |
| s565 => s324 | c1*(kf*s565-kb*s324) | kb=0.1 per_sec; kf=1.0 per_sec |
| s310 => s331 | c1*kf*s310 | kf=4.63E-5 per_sec |
| s351 + s349 => s355 | c1*(kf*s351*s349-kb*s355) | kb=0.1 per_sec; kf=0.01 per_uM_per_sec |
| s539 => s359 + s293 | c1*Vmax*s539 | Vmax=3.67 per_sec |
| s358 + s294 => s520 | c1*((1+ratio)*Vmax*s294*s358/Km-Vmax*ratio*s520) | Vmax=3.67 per_sec; Km=10.019 microMolar; ratio=1.7299 dimensionless |
| s512 => s360 + s294 | c1*Vmax*s512 | Vmax=3.67 per_sec |
| s520 => s359 + s294 | c1*Vmax*s520 | Vmax=3.67 per_sec |
| s280 + s289 => s295 | c1*(kf*s280*s289-kb*s295) | kb=0.01 per_sec; kf=10.0 per_uM_per_sec |
| s358 + s295 => s513 | c1*((1+ratio)*Vmax*s295*s358/Km-Vmax*ratio*s513) | Vmax=3.67 per_sec; Km=10.019 microMolar; ratio=1.7299 dimensionless |
| s359 + s295 => s506 | c1*((1+ratio)*Vmax*s295*s359/Km-Vmax*ratio*s506) | Vmax=3.67 per_sec; Km=10.019 microMolar; ratio=1.7299 dimensionless |
(added: 24 Jan 2007, 01:59:09, updated: 24 Jan 2007, 01:59:09)