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PTEN as an effector in the signaling of antimigratory G protein-coupled receptor

Teresa Sanchez1, Shobha Thangada, Ming-Tao Wu

  • 1Center for Vascular Biology, Department of Cell Biology, University of Connecticut Health Center, Farmington, CT 06030, USA.

Proceedings of the National Academy of Sciences of the United States of America
|March 15, 2005
PubMed

Insights

Sphingosine 1-phosphate (S1P) inhibits cell migration via the S1P2 receptor (S1P2R) by activating phosphatase and tensin homolog (PTEN). This study reveals S1P2R actively regulates PTEN phosphatase activity to control cell movement.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • PTEN (phosphatase and tensin homolog deleted on chromosome 10) is a crucial tumor suppressor involved in cell migration and invasion.
  • The physiological regulation of PTEN by cell surface receptors is not well understood.
  • G protein-coupled receptors (GPCRs) play significant roles in cellular signaling pathways.

Purpose of the Study:

  • To investigate the role of PTEN as a signaling intermediate in S1P2R-mediated inhibition of cell migration.
  • To elucidate the mechanism by which S1P2R regulates PTEN activity.
  • To determine the relationship between PTEN and Rho GTPase in S1P2R signaling.

Main Methods:

  • Utilized dominant-negative PTEN and Rho GTPase constructs.
  • Employed Pten(DeltaloxP/DeltaloxP) mouse embryonic fibroblasts to assess S1P effects.
  • Performed co-immunoprecipitation assays to detect S1P2R and PTEN interactions.
  • Measured PTEN phosphatase activity in membrane fractions.
  • Analyzed tyrosine phosphorylation of PTEN.

Main Results:

  • S1P2R inhibition of cell migration was dependent on PTEN.
  • PTEN acts downstream of Rho GTPase in the S1P2R signaling pathway.
  • S1P2R activation led to co-immunoprecipitation of S1P2R and PTEN.
  • S1P2R signaling increased PTEN phosphatase activity and tyrosine phosphorylation of PTEN.

Conclusions:

  • The S1P2R receptor actively regulates PTEN phosphatase activity through a Rho GTPase-dependent pathway to inhibit cell migration.
  • GPCR regulation of PTEN may represent a general mechanism in signaling events controlling cell migration and invasion.

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