Abstract
Protein-tyrosine phosphatase (PTP)-PEST (PTPN12) is ubiquitously expressed. It is essential for normal embryonic development and embryonic viability in mice. Herein we addressed the involvement of PTP-PEST in endothelial cell functions using a combination of genetic and biochemical approaches. By generating primary endothelial cells from an inducible PTP-PEST-deficient mouse, we found that PTP-PEST is not needed for endothelial cell differentiation and proliferation or for the control of endothelial cell permeability. Nevertheless, it is required for integrin-mediated adhesion and migration of endothelial cells. PTP-PEST-deficient endothelial cells displayed increased tyrosine phosphorylation of Cas, paxillin, and Pyk2, which were previously also implicated in integrin functions. By eliminating PTP-PEST in endothelial cells in vivo, we obtained evidence that expression of PTP-PEST in endothelial cells is required for normal vascular development and embryonic viability. Therefore, PTP-PEST is a key regulator of integrin-mediated functions in endothelial cells seemingly through its capacity to control Cas, paxillin, and Pyk2. This function explains at least in part the essential role of PTP-PEST in embryonic development and viability.
Highlights
Protein-tyrosine phosphatase (PTP)-PEST is a phosphatase essential for embryonic viability
We bred mice carrying a conditional allele of the PTP-PEST-encoding gene (Ptpn12fl/fl) with mice expressing an estrogen-responsive Cre (Cre-ERT2), under the control of the ubiquitin C (UBC) promoter (Fig. 1A) [34]
Immunoblot analyses of total cell lysates with antiPTP-PEST antibodies showed that cells from tamoxifen-fed Ptpn12fl/fl;UBC-Cre-ERT2ϩ mice completely lacked expression of PTP-PEST (Fig. 1B)
Summary
PTP-PEST is a phosphatase essential for embryonic viability. Results: PTP-PEST is critical for adhesion and migration of endothelial cells. PTP-PEST is a key regulator of integrin-mediated functions in endothelial cells seemingly through its capacity to control Cas, paxillin, and Pyk. PTP-PEST is a key regulator of integrin-mediated functions in endothelial cells seemingly through its capacity to control Cas, paxillin, and Pyk2 This function explains at least in part the essential role of PTP-PEST in embryonic development and viability. Using primary endothelial cells from an inducible PTP-PESTdeficient mouse, we found that PTP-PEST is required for migration and adhesion of endothelial cells, but not for proliferation, differentiation, and modulation of permeability to macromolecules by these cells This function correlates with the capacity of PTP-PEST to dephosphorylate Cas, paxillin, and Pyk. Studies of a mouse in which PTP-PEST was eliminated in endothelial cells provided evidence that the function of PTP-PEST in endothelial cells is critical for normal vascular development and embryonic viability
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call