Vascular endothelial cadherin controls VEGFR-2 internalization and signaling from intracellular compartments.

摘要: Receptor endocytosis is a fundamental step in controlling the magnitude, duration, and nature of cell signaling events. Confluent endothelial cells are contact inhibited their growth respond poorly to proliferative signals vascular factor (VEGF). In previous study, we found that association cadherin (VEC) with VEGF receptor (VEGFR) type 2 contributes density-dependent inhibition (Lampugnani, G.M., A. Zanetti, M. Corada, T. Takahashi, G. Balconi, F. Breviario, Orsenigo, Cattelino, R. Kemler, T.O. Daniel, E. Dejana. 2003. J. Cell Biol. 161:793–804). present describe mechanism through which VEC reduces VEGFR-2 signaling. We induces clathrin-dependent internalization VEGFR-2. When absent or not engaged at junctions, internalized more rapidly remains endosomal compartments for longer time. Internalization does terminate its signaling; instead, phosphorylated, codistributes active phospholipase C–γ, activates p44/42 mitogen-activated protein kinase phosphorylation proliferation. Inhibition reestablishes growth, whereas silencing junction-associated density-enhanced phosphatase-1/CD148 phosphatase restores Thus, limits proliferation by retaining membrane preventing into compartments.