Corti et al. show that the proteoglycan Syndecan-2 (Sdc2) regulates the interaction between phosphatase DEP1 and the vascular endothelial growth factor receptor VEGFR2. Depletion or antibody-mediated inhibition of Sdc2 causes compromised internalization of DEP1, and excessive expression of DEP1 in the membrane results in large dephosphorylation specifically of VEGFR2 Y951 residue, leading to reduced VEGF-mediated permeabilization without affecting other VEGF-mediated functions, with beneficial effects in animal models of skin edema and brain focal stroke.
- F. Corti
- E. Ristori
- M. Simons