Related Experiment Video
Updated: Jul 17, 2026

Imaging G-protein Coupled Receptor (GPCR)-mediated Signaling Events that Control Chemotaxis of Dictyostelium Discoideum
Published on: September 20, 2011
PtdIns(3,4,5)P(3)-dependent and -independent roles for PTEN in the control of cell migration
Nick R Leslie1, Xuesong Yang, C Peter Downes
1Division of Molecular Physiology, University of Dundee, Dundee, DD1 5EH, Scotland, United Kingdom. n.r.leslie@dundee.ac.uk
Background:
Phosphatase and tensin homolog (PTEN) mediates many of its effects on proliferation, growth, survival, and migration through its PtdIns(3,4,5)P(3) lipid phosphatase activity, suppressing phosphoinositide 3-kinase (PI3K)-dependent signaling pathways. PTEN also possesses a protein phosphatase activity, the role of which is less well characterized.
Results:
We have investigated the role of PTEN in the control of cell migration of mesoderm cells ingressing through the primitive streak in the chick embryo. Overexpression of PTEN strongly inhibits the epithelial-to-mesenchymal transition (EMT) of mesoderm cells ingressing through the anterior and middle primitive streak, but it does not affect EMT of cells located in the posterior streak. The inhibitory activity on EMT is completely dependent on targeting PTEN through its C-terminal PDZ binding site, but can be achieved by a PTEN mutant (PTEN G129E) with only protein phosphatase activity. Expression either of PTEN lacking the PDZ binding site or of the PTEN C2 domain, or inhibition of PI3K through specific inhibitors, does not inhibit EMT, but results in a loss of both cell polarity and directional migration of mesoderm cells. The PTEN-related protein TPTE, which normally lacks any detectable lipid and protein phosphatase activity, can be reactivated through mutation, and only this reactivated mutant leads to nondirectional migration of these cells in vivo.
Conclusions:
PTEN modulates cell migration of mesoderm cells in the chick embryo through at least two distinct mechanisms: controlling EMT, which involves its protein phosphatase activity; and controlling the directional motility of mesoderm cells, through its lipid phosphatase activity.
Insights
Phosphatase and tensin homolog (PTEN) controls mesoderm cell migration in chick embryos. It regulates epithelial-to-mesenchymal transition (EMT) via protein phosphatase activity and directional movement through lipid phosphatase activity.
Area of Science:
- Developmental Biology
- Cell Biology
- Molecular Biology
Background:
- Phosphatase and tensin homolog (PTEN) is a tumor suppressor that regulates cell signaling pathways.
- PTEN has both lipid and protein phosphatase activities, with the latter's role being less understood.
- PTEN's lipid phosphatase activity suppresses phosphoinositide 3-kinase (PI3K)-dependent signaling.
Purpose of the Study:
- To investigate the role of PTEN in controlling mesoderm cell migration during gastrulation in chick embryos.
- To determine the specific phosphatase activities of PTEN involved in cell migration and epithelial-to-mesenchymal transition (EMT).
Main Methods:
- Overexpression of wild-type PTEN and PTEN mutants in chick embryos.
- Inhibition of PI3K signaling using specific inhibitors.
- Analysis of cell migration, EMT, cell polarity, and directional movement of mesoderm cells.
Main Results:
- PTEN overexpression inhibited EMT in anterior and middle primitive streak mesoderm cells, dependent on its PDZ binding site.
- A PTEN mutant with only protein phosphatase activity (PTEN G129E) retained the ability to inhibit EMT.
- Inhibition of PI3K or expression of PTEN mutants lacking PDZ binding sites disrupted cell polarity and directional migration.
- Reactivated TPTE mutants caused nondirectional cell migration.
Conclusions:
- PTEN regulates mesoderm cell migration through distinct mechanisms involving both protein and lipid phosphatase activities.
- Protein phosphatase activity of PTEN is crucial for controlling EMT during gastrulation.
- Lipid phosphatase activity of PTEN is essential for maintaining cell polarity and directional migration.
Related Concept Videos
Cell Migration
Cell Migration
Abnormal Proliferation
PI3K/mTOR/AKT Signaling Pathway
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Cell Polarization by Rho Proteins