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Title: Role of PlGF in the intra- and intermolecular cross talk between the VEGF receptors Flt1 and Flk1
Authors: Autiero, Monica ×
Waltenberger, Johannes
Communi, Didier
Kranz, Andrea
Moons, Lieve
Lambrechts, Diether
Kroll, Jens
Plaisance, Stephane
De Mol, Maria
Bono, Françoise
Kliche, Stefanie
Fellbrich, Guido
Ballmer-Hofer, Kurt
Maglione, Domenico
Mayr-Beyrle, Ulrike
Dewerchin, Mieke
Dombrowski, Saskia
Stanimirovic, Danica
Van Hummelen, Paul
Dehio, Christoph
Hicklin, Daniel J
Persico, Graziella
Herbert, Jean-Marc
Communi, David
Shibuya, Masabumi
Collen, Desire
Conway, Edward
Carmeliet, Peter #
Issue Date: Jul-2003
Series Title: Nature medicine vol:9 issue:7 pages:936-43
Abstract: Therapeutic angiogenesis is likely to require the administration of factors that complement each other. Activation of the receptor tyrosine kinase (RTK) Flk1 by vascular endothelial growth factor (VEGF) is crucial, but molecular interactions of other factors with VEGF and Flk1 have been studied to a limited extent. Here we report that placental growth factor (PGF, also known as PlGF) regulates inter- and intramolecular cross talk between the VEGF RTKs Flt1 and Flk1. Activation of Flt1 by PGF resulted in intermolecular transphosphorylation of Flk1, thereby amplifying VEGF-driven angiogenesis through Flk1. Even though VEGF and PGF both bind Flt1, PGF uniquely stimulated the phosphorylation of specific Flt1 tyrosine residues and the expression of distinct downstream target genes. Furthermore, the VEGF/PGF heterodimer activated intramolecular VEGF receptor cross talk through formation of Flk1/Flt1 heterodimers. The inter- and intramolecular VEGF receptor cross talk is likely to have therapeutic implications, as treatment with VEGF/PGF heterodimer or a combination of VEGF plus PGF increased ischemic myocardial angiogenesis in a mouse model that was refractory to VEGF alone.
URI: 
ISSN: 1078-8956
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular and Vascular Biology
Vesalius Research Centre (-)
Animal Physiology and Neurobiology Section - miscellaneous
Laboratory of Translational Genetics (Vesalius Research Center) (+)
Laboratory of Angiogenesis and Vascular Metabolism (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

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