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VEGF receptor 2/-3 heterodimers detected in situ by proximity ligation on angiogenic sprouts
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
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2010 (English)In: EMBO Journal, ISSN 0261-4189, E-ISSN 1460-2075, Vol. 29, no 8, 1377-1388 p.Article in journal (Refereed) Published
Abstract [en]

The vascular endothelial growth factors VEGFA and VEGFC are crucial regulators of vascular development. They exert their effects by dimerization and activation of the cognate receptors VEGFR2 and VEGFR3. Here, we have used in situ proximity ligation to detect receptor complexes in intact endothelial cells. We show that both VEGFA and VEGFC potently induce formation of VEGFR2/-3 heterodimers. Receptor heterodimers were found in both developing blood vessels and immature lymphatic structures in embryoid bodies. We present evidence that heterodimers frequently localize to tip cell filopodia. Interestingly, in the presence of VEGFC, heterodimers were enriched in the leading tip cells as compared with trailing stalk cells of growing sprouts. Neutralization of VEGFR3 to prevent heterodimer formation in response to VEGFA decreased the extent of angiogenic sprouting. We conclude that VEGFR2/-3 heterodimers on angiogenic sprouts induced by VEGFA or VEGFC may serve to positively regulate angiogenic sprouting.

Place, publisher, year, edition, pages
2010. Vol. 29, no 8, 1377-1388 p.
National Category
Medical Genetics
Identifiers
URN: urn:nbn:se:uu:diva-123738DOI: 10.1038/emboj.2010.30ISI: 000276927000007PubMedID: 20224550OAI: oai:DiVA.org:uu-123738DiVA: diva2:315566
Available from: 2010-04-29 Created: 2010-04-29 Last updated: 2017-12-12Bibliographically approved

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Söderberg, OlaKreuger, JohanClaesson-Welsh, Lena

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Söderberg, OlaKreuger, JohanClaesson-Welsh, Lena
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Department of Genetics and PathologyDepartment of Medical Biochemistry and Microbiology
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