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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.

Related Publication
  • 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.
Yu-ichi Ozaki

Metadata information

BioModels Database MODEL7944007619
BioModels Database BIOMD0000000088
Gene Ontology regulation of Rho protein signal transduction
Gene Ontology actin cytoskeleton organization
PubMed 16923126
Taxonomy Homo sapiens

Curation status

Name Description Size Actions

Model files

BIOMD0000000088_url.xml SBML L2V1 representation of Maeda2006_MyosinPhosphorylation 241.65 KB Preview | Download

Additional files

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
  • Version: 2 public model Download this version
    • Submitted on: 08-Apr-2016 16:36:16
    • Submitted by: Yu-ichi Ozaki
    • With comment: Current version of Maeda2006_MyosinPhosphorylation
  • Version: 1 public model Download this version
    • Submitted on: 28-Jan-2007 23:57:52
    • Submitted by: Yu-ichi Ozaki
    • With comment: Original import of BIOMD0000000088.xml.origin

(*) You might be seeing discontinuous revisions as only public revisions are displayed here. Any private revisions unpublished model revision of this model will only be shown to the submitter and their collaborators.

: Variable used inside SBML models

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
Curator's comment:
(added: 24 Jan 2007, 01:59:09, updated: 24 Jan 2007, 01:59:09)
Plots correspond to Fig 2B, D, F, and 2H of the paper. Results obtained from Cell Designer.