Heterodimerization with vascular endothelial growth factor receptor-2 (VEGFR-2) is necessary for VEGFR-3 activity
Alam, Antoine × Herault, Jean-Pascal Barron, Pauline Favier, Benoit Fons, Pierre Delesque-Touchard, Nathalie Senegas, Isabelle Laboudie, Patricia Bonnin, Jacques Cassan, Cecile Savi, Pierre Ruggeri, Bruce Carmeliet, Peter Bono, Françoise Herbert, Jean-Marc #
Biochemical and Biophysical Research Communications vol:324 issue:2 pages:909-15
VEGFR-3 is essential for vascular development and maintenance of lymphatic vessel's integrity. Little is known about its cooperative effect with other receptors of the same family. Contrary to VEGFR-2, stimulation of VEGFR-3 by VEGF-C and -D failed to enhance its phosphorylation either in HEK293T or in PAE cells. These ligands were unable to induce angiogenesis of PAEC expressing VEGFR-3 alone. In the presence of VEGFR-2, VEGF-C and -D induced heterodimerization of VEGFR-3 with VEGFR-2. This heterodimerization was associated with enhanced VEGFR-3 phosphorylation and subsequent cellular responses as evidenced by the formation of capillary-like structures in PAE cells and proliferation of primary human endothelial cells expressing both receptors. Taken together, these results show for the first time that VEGFR-3 needs to be associated to VEGFR-2 to induce ligand-dependent cellular responses.