title: The phosphatase PTP-PEST/PTPN12 regulates endothelial cell migration and adhesion, but not permeability, and controls vascular development and embryonic viability.
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.
authors.affiliation: Laboratories of Molecular Oncology, Clinical Research Institute of Montréal, Montréal, Québec H2W 1R7, Canada.
authors.forename: Cleiton Martins
authors.initials: CM
authors.lastname: Souza
authors.forename: Dominique
authors.initials: D
authors.lastname: Davidson
authors.forename: Inmoo
authors.initials: I
authors.lastname: Rhee
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Gratton
authors.forename: Elaine C
authors.initials: EC
authors.lastname: Davis
authors.forename: André
authors.initials: A
authors.lastname: Veillette
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000196:embryology*; D002448:Cell Adhesion; D002454:Cell Differentiation; D002463:Cell Membrane Permeability; D002465:Cell Movement; D049109:Cell Proliferation; D048430:Cell Shape; D004622:Embryo, Mammalian / Q000166:cytology / Q000201:enzymology*; D042783:Endothelial Cells / Q000166:cytology* / Q000201:enzymology*; D005260:Female; D051418:Focal Adhesion Kinase 2 / Q000378:metabolism; D005838:Genotype; D016023:Integrins / Q000378:metabolism; D007365:Intercellular Junctions / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D051419:Paxillin / Q000378:metabolism; D010766:Phosphorylation; D054594:Protein Tyrosine Phosphatase, Non-Receptor Type 12 / Q000172:deficiency / Q000378:metabolism*
chemical_list: D016023:Integrins; D051419:Paxillin; D051418:Focal Adhesion Kinase 2; C496053:Ptk2b protein, mouse; D054594:Protein Tyrosine Phosphatase, Non-Receptor Type 12; C516739:Ptpn12 protein, mouse