JCB logo
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 7 August 2006. doi:10.1083/jcb.200602080
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 174, Number 4, 593-604
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 2252K)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lampugnani, M. G.
Right arrow Articles by Dejana, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lampugnani, M. G.
Right arrow Articles by Dejana, E.
Related Collections
Right arrowRelated Article
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Article

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



Maria Grazia Lampugnani1,2, Fabrizio Orsenigo1, Maria Cristina Gagliani4, Carlo Tacchetti4, and Elisabetta Dejana1,2,3

1 IFOM, Fondazione Italiana per la Ricerca sul Cancro Institute of Molecular Oncology, 2 Mario Negri Institute for Pharmacological Research, and 3 Department of Biomolecular and Biotechnological Sciences, Faculty of Sciences, University of Milan, 20139 Milan, Italy
4 Department of Experimental Medicine, University of Genova, 16146 Genova, Italy

Correspondence to Elisabetta Dejana: elisabetta.dejana{at}ifom-ieo-campus.it

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

Abbreviations used in this paper: EEA-1, early endosomal antigen-1; DEP-1, density-enhanced phosphatase-1; GSH, glutathione; HUVEC, human umbilical vein endothelial cell; PY, phosphotyrosine; VEC, vascular endothelial cadherin; VEGFR, VEGF receptor.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?

Related Article

Cadherin stops receptor endocytosis
Nicole LeBrasseur
J. Cell Biol. 2006 174: 475a. [Full Text] [PDF]



This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents