Phosphoproteomics of MEFs with loss-of-function PTEN mutations
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Q Exactive
ORGANISM(S): Mus Musculus (mouse)
TISSUE(S): Primary Cell, Early Embryonic Cell, Fibroblast
DISEASE(S): Disease Free
SUBMITTER: 
Hon Yan Kelvin Yip
LAB HEAD: Antonella Papa
PROVIDER: PXD016184 | Pride | 2020-10-15
REPOSITORIES: Pride
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Project 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:
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
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.
| MODEL1704190000 | BioModels
Project description:Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a tumor suppressor that negatively regulates cell survival and proliferation by antagonizing phosphatidylinositol 3-kinase(PI3K)/protein kinase B(PKB/Akt) signaling. Loss of heterozygosity (LOH) of PTEN, reduced expression of PTEN and overexpression of phosphorylated Akt are frequently found in human gastric cancer, and their changes correlate with tumor progression and prognosis. Previous studies have shown that the deregulated miRNAs in human gastric cancer play important roles in gastric cancer cell proliferation, apoptosis and inflammation. However, miRNAs downstream PTEN/Akt signaling is poorly investigated. To clarify whether PTEN is involved in gastric tumorigenesis, we have generated a gastric epithelium specific PTEN knockout mouse which exhibited gastric tumor formation with enhanced cell proliferation.So the objectives of the microarray experiment were to, a) screen miRNAs which might be regulated by PTEN/Akt signaling by comparing the miRNA expression profiles between PTEN deficient and control gastric epithelia. 2) explore the microRNA mechanism involved in gastric cell proliferation and gastric tumorigenesis. miRNA profiling of mouse gastric epithelium,comparing Pten mutant mouse with controls. 4 samples. Experiments in 2 different time point, 20 days and 60 days after birth, 2 Biological replicates. Mutant tissue vs. controls from mixture of 3-4 mouse.
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