The p85beta regulatory subunit of PI3K serves as a substrate for PTEN protein phosphatase activity during insulin

Related Experiment Video

Updated: Jun 12, 2026

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry
08:07

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry

Published on: July 26, 2019

Jiman He1, Suzanne de la Monte, Jack R Wands

  • 1Liver Research Center, Warren Alpert Medical School of Brown University, Providence, RI 02913, United States.

Biochemical and Biophysical Research Communications
|June 3, 2010
PubMed

Insights

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) dephosphorylates the PI3K p85beta subunit, a key player in insulin signaling. This action impacts cell migration, motility, and invasion, offering insights into cancer progression.

Area of Science:

  • Molecular Biology
  • Cellular Signaling
  • Oncology

Background:

  • The tumor suppressor gene PTEN (Phosphatase and tensin homolog deleted on chromosome 10) is frequently mutated in various cancers.
  • The precise protein phosphatase activity of PTEN remains incompletely understood.
  • PTEN plays a critical role in regulating cell growth and survival pathways.

Purpose of the Study:

  • To investigate the specific targets and activity of PTEN within the insulin signaling pathway.
  • To elucidate the role of PTEN in the dephosphorylation of phosphatidylinositol 3-kinase (PI3K) subunits.
  • To understand how PTEN's phosphatase activity influences downstream cellular processes like migration and invasion.

Main Methods:

  • Utilized cell lines such as Huh-7 and HEK 293 to study insulin-stimulated phosphorylation.
  • Investigated the interaction and dephosphorylation of PI3K subunits by PTEN.
  • Analyzed the impact of PTEN activity on downstream signaling events.

Main Results:

  • Demonstrated that insulin stimulates the phosphorylation of tyrosine and threonine/proline residues on the p85 regulatory subunit of PI3K.
  • Identified the p85beta subunit as the specific target for PTEN binding and dephosphorylation.
  • Confirmed that PTEN phosphatase is active against PI3K p85beta, affecting a protein crucial for insulin signaling.

Conclusions:

  • PTEN directly dephosphorylates the PI3K p85beta subunit, modulating insulin signaling.
  • This PTEN activity influences cellular behaviors, including migration, motility, and invasion.
  • Findings provide a clearer understanding of PTEN's function in cancer and metabolic pathways.

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