title: Substitution of C-terminus of VEGFR-2 with VEGFR-1 promotes VEGFR-1 activation and endothelial cell proliferation.
abstract: VEGFR-1 is devoid of ligand-dependent tyrosine autophosphorylation and its activation is not associated with proliferation of endothelial cells. The molecular mechanism responsible for this characteristic of VEGFR-1 is not known. In this study, we show that VEGFR-1 is devoid of ligand-dependent downregulation and failed to stimulate intracellular calcium release, cell migration and angiogenesis in vitro. To understand the molecular mechanisms responsible for the poor tyrosine autophosphorylation of VEGFR-1, we have either deleted the carboxyl terminus of VEGFR-1 or exchanged it with the carboxyl terminus of VEGFR-2. The deletion of carboxyl terminus of VEGFR-1 did not reverse its defective ligand-dependent autophosphorylation. The carboxyl terminus-swapped VEGFR-1, however, displayed ligand-dependent autophosphorylation, downregulation and also conveyed strong mitogenic responses. Thus, the carboxyl tail of VEGFR-1 restrains the ligand-dependent kinase activation and downregulation of VEGFR-1 and its ability to convey the angiogenic responses in endothelial cells.
authors.affiliation: Departments of Ophthalmology and Biochemistry, School of Medicine, Boston University, 715 Albany Street, Boston, MA 02118, USA.
authors.forename: Rosana D
authors.initials: RD
authors.lastname: Meyer
authors.forename: Amrik
authors.initials: A
authors.lastname: Singh
authors.forename: Fredric
authors.initials: F
authors.lastname: Majnoun
authors.forename: Catharina
authors.initials: C
authors.lastname: Latz
authors.forename: Kameran
authors.initials: K
authors.lastname: Lashkari
authors.forename: Nader
authors.initials: N
authors.lastname: Rahimi
mesh_terms: D000818:Animals; D002455:Cell Division / Q000502:physiology; D015536:Down-Regulation; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D008024:Ligands; D010766:Phosphorylation; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D008024:Ligands; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2