Model for a role of DMP1 in VEGF-induced signaling. In the presence of VEGF, VEGFR-2 is activated through phosphorylation (bold red “P”). Src is subsequently phosphorylated on Tyr416, whereas it is dephosphorylated on Tyr527, which results in its activation. Active Src thereby inactivates VE-cadherin function through phosphorylation of its intracytoplasmic domain tyrosines, particularly on Tyr685. In the presence of VEGF and on DMP1 binding to CD44, VE-cadherin expression level is increased. On the one hand, this VE-cadherin up-regulation induces p27^Kip1 expression and cell-cycle arrest, thus mimicking contact inhibition of growth; on the other hand, active VE-cadherin sequestrates VEGFR-2 and therefore impedes its activation through the inhibition of its phosphorylation. DMP1 pretreatment partially impairs (light red “P”) VE-cadherin phosphorylation on its Tyr685, which still allows the recruitment of Csk. In turn, DMP1 inactivated-VEGFR-2 is not able to phosphorylate further Src on Tyr416, whereas it is phosphorylated on Tyr527 by Csk, the expression of which is induced in the presence of DMP1.