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Role of PlGF in the intra- and intermolecular cross talk between the VEGF receptors Flt1 and Flk1

Autiero, M. and Waltenberger, J. and Communi, D. and Kranz, A. and Moons, L. and Lambrechts, D. and Kroll, J. and Plaisance, S. and De Mol, M. and Bono, F. and Kliche, S. and Fellbrich, G. and Ballmer-Hofer, K. and Maglione, D. and Mayr-Beyrle, U. and Dewerchin, M. and Dombrowski, S. and Stanimirovic, D. and Van Hummelen, P. and Dehio, C. and Hicklin, D. J. and Persico, G. and Herbert, J. -M. and Shibuya, M. and Collen, D. and Conway, E. M. and Carmeliet, P.. (2003) Role of PlGF in the intra- and intermolecular cross talk between the VEGF receptors Flt1 and Flk1. Nature medicine, Vol. 9, H. 7. pp. 936-943.

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Official URL: http://edoc.unibas.ch/dok/A5259013

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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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Infection Biology > Molecular Microbiology (Dehio)
UniBasel Contributors:Dehio, Christoph
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Nature Publishing
ISSN:1078-8956
Note:Publication type according to Uni Basel Research Database: Journal article
Last Modified:22 Mar 2012 14:20
Deposited On:22 Mar 2012 13:21

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