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Published on: July 17, 2020

Evidence That the Protein Phosphatase Activity of PTEN Contributes to Embryonic Development and Tumor Suppression

Priyanka Tibarewal1,2,3, Laura Spinelli1,2, Nisha Kriplani1

  • 1Institute of Biological Chemistry, Biophysics and Bioengineering, Heriot Watt University, Edinburgh, UK.

Cancer Science
|July 19, 2026
PubMed

Insights

The protein phosphatase activity of PTEN (phosphatase and tensin homolog deleted on chromosome ten) is crucial for embryonic development and tumor suppression. This study shows PTEN

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • PTEN (phosphatase and tensin homolog deleted on chromosome ten) is a critical tumor suppressor.
  • Its function is often impaired in various cancers.
  • PTEN possesses both lipid and protein phosphatase activities, regulating the PI3K signaling pathway.

Purpose of the Study:

  • To investigate the specific roles of PTEN's protein phosphatase activity in vivo.
  • To generate and analyze mice with a mutation selectively disabling PTEN's protein phosphatase activity (PTEN-Y138L).

Main Methods:

  • Generation of germline knock-in mice expressing PTEN-Y138L.
  • Analysis of homozygous PtenY138L/Y138L embryonic lethality.
  • Assessment of AKT phosphorylation in primary MEFs and thymocytes.
  • Evaluation of tumor development and survival in heterozygous Pten+/Y138L mice.

Main Results:

  • Homozygous PtenY138L/Y138L mice exhibit embryonic lethality before E10.5.
  • PTEN-Y138L effectively regulates PI3K signaling in vivo, maintaining low AKT phosphorylation levels.
  • Heterozygous Pten+/Y138L mice show reduced survival and develop multiple tumors.

Conclusions:

  • PTEN's protein phosphatase activity, in addition to its lipid phosphatase activity, is essential for embryonic development.
  • PTEN's protein phosphatase activity plays a vital role in tumor suppression.
  • Disruption of PTEN's protein phosphatase activity leads to developmental defects and increased cancer susceptibility.
Keywords:
AKTPI3KPTENmicephosphatase

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