Phosphatase activities on PI(3,4,5)P3 and PI(3,4)P2

  public model
Model Identifier
MODEL1704190000
Short description
Phosphatase activities on PI(3,4,5)P3 and PI(3,4)P2
This model describes the action of various phosphatases on
PI(3,4,5)P3 and PI(3,4)P2, in response to a stimulation by EGF. It
contains boolean switches to simulate knock-down and knock-out of
phosphatases as well as inhibition of PI3 kinase.

This model is described in the article:

Mouhannad Malek, Anna Kielkowska, Tamara Chessa, Karen E. Anderson, David Barneda, P?nar Pir, Hiroki Nakanishi, Satoshi Eguchi, Atsushi Koizumi, Junko Sasaki, Véronique Juvin, Vladimir Y. Kiselev, Izabella Niewczas, Alexander Gray, Alexandre Valayer, Dominik Spensberger, Marine Imbert, Sergio Felisbino, Tomonori Habuchi, Soren Beinke, Sabina Cosulich, Nicolas Le Novère, Takehiko Sasaki, Jonathan Clark, Phillip T. Hawkins and Len R. Stephens
Molecular Cell

Abstract:

The PI3K signaling pathway regulates cell growth and movement and is heavily mutated in cancer. Class I PI3Ks synthesize the lipid messenger PI(3,4,5)P3. PI(3,4,5)P3 can be dephosphorylated by 3- or 5-phosphatases, the latter producing PI(3,4)P2. The PTEN tumor suppressor is thought to function primarily as a PI(3,4,5)P3 3-phosphatase, limiting activation of this pathway. Here we show that PTEN also functions as a PI(3,4)P2 3-phosphatase, both in vitro and in vivo. PTEN is a major PI(3,4)P2 phosphatase in Mcf10a cytosol, and loss of PTEN and INPP4B, a known PI(3,4)P2 4-phosphatase, leads to synergistic accumulation of PI(3,4)P2, which correlated with increased invadopodia in epidermal growth factor (EGF)-stimulated cells. PTEN deletion increased PI(3,4)P2 levels in a mouse model of prostate cancer, and it inversely correlated with PI(3,4)P2 levels across several EGF-stimulated prostate and breast cancer lines. These results point to a role for PI(3,4)P2 in the phenotype caused by loss-of-function mutations or deletions in PTEN.

This model is hosted on BioModels Database and identified by: MODEL1704190000.

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.

Format
SBML (L2V4)
Related Publication
  • PTEN Regulates PI(3,4)P2 Signaling Downstream of Class I PI3K
  • Mouhannad Malek, Anna Kielkowska, Tamara Chessa, Karen E. Anderson, David Barneda, P?nar Pir, Hiroki Nakanishi, Satoshi Eguchi, Atsushi Koizumi, Junko Sasaki, Véronique Juvin, Vladimir Y. Kiselev, Izabella Niewczas, Alexander Gray, Alexandre Valayer, Dominik Spensberger, Marine Imbert, Sergio Felisbino, Tomonori Habuchi, Soren Beinke, Sabina Cosulich, Nicolas Le Novère, Takehiko Sasaki, Jonathan Clark, Phillip T. Hawkins and Len R. Stephens
  • Molecular Cell , DOI: 10.1016/j.molcel.2017.09.024
  • Babraham Institute, Cambridge, UK
  • The PI3K signaling pathway regulates cell growth and movement and is heavily mutated in cancer. Class I PI3Ks synthesize the lipid messenger PI(3,4,5)P3. PI(3,4,5)P3 can be dephosphorylated by 3- or 5-phosphatases, the latter producing PI(3,4)P2. The PTEN tumor suppressor is thought to function primarily as a PI(3,4,5)P3 3-phosphatase, limiting activation of this pathway. Here we show that PTEN also functions as a PI(3,4)P2 3-phosphatase, both in vitro and in vivo. PTEN is a major PI(3,4)P2 phosphatase in Mcf10a cytosol, and loss of PTEN and INPP4B, a known PI(3,4)P2 4-phosphatase, leads to synergistic accumulation of PI(3,4)P2, which correlated with increased invadopodia in epidermal growth factor (EGF)-stimulated cells. PTEN deletion increased PI(3,4)P2 levels in a mouse model of prostate cancer, and it inversely correlated with PI(3,4)P2 levels across several EGF-stimulated prostate and breast cancer lines. These results point to a role for PI(3,4)P2 in the phenotype caused by loss-of-function mutations or deletions in PTEN.
Contributors
Nicolas Le Novère

Metadata information

is
BioModels Database MODEL1704190000
hasProperty
Mathematical Modelling Ontology Ordinary differential equation model

Curation status
Non-curated


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MODEL1704190000_url.xml SBML L2V4 representation of Phosphatase activities on PI(3,4,5)P3 and PI(3,4)P2 88.19 KB Preview | Download

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MODEL1704190000-biopax3.owl Auto-generated BioPAX (Level 3) 32.99 KB Preview | Download
MODEL1704190000.sci Auto-generated Scilab file 67.00 bytes Preview | Download
MODEL1704190000_urn.xml Auto-generated SBML file with URNs 87.79 KB Preview | Download
MODEL1704190000-biopax2.owl Auto-generated BioPAX (Level 2) 22.17 KB Preview | Download
MODEL1704190000.xpp Auto-generated XPP file 7.90 KB Preview | Download
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MODEL1704190000.vcml Auto-generated VCML file 99.80 KB Preview | Download
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MODEL1704190000.svg Auto-generated Reaction graph (SVG) 31.71 KB Preview | Download

  • Model originally submitted by : Nicolas Le Novère
  • Submitted: 19-Apr-2017 10:55:01
  • Last Modified: 20-Oct-2017 15:49:15
Revisions
  • Version: 2 public model Download this version
    • Submitted on: 20-Oct-2017 15:49:15
    • Submitted by: Nicolas Le Novère
    • With comment: Current version of MODEL1704190000
  • Version: 1 public model Download this version
    • Submitted on: 19-Apr-2017 10:55:01
    • Submitted by: Nicolas Le Novère
    • With comment: Original import of MODEL1704190000
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