VEGFR-3 ligand-binding and kinase activity are required for lymphangiogenesis but not for angiogenesis

119Citations
Citations of this article
108Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

Although VEGFR-3 deficiency disrupts blood vascular development during early embryogenesis, the underlying mechanism was not clear. To characterize its function in angiogenesis and lymphangiogenesis, we employed two genetically modified mouse models in this study, targeting the coding region for the ligand-binding domain (Vegfr3ΔLBD) or the tyrosine kinase domain with an inactivation point mutation (Vegfr3TKmut). We show that lymphatic growth was disrupted in Vegfr3ΔLBD/ΔLBD and Vegfr3TKmut/TKmut mice, but blood vessels developed normally in both embryo and yolk sac. Interestingly, in Vegfr3 ΔLBD/ΔLBD but not Vegfr3TKmut/TKmut mice, lymph sac was present but there was lack of lymphangiogenic sprouting. We further demonstrate that both the wild-type and mutant forms of VEGFR-3 could form heterodimers with VEGFR-2, and decreased the level of phospho-VEGFR-2 and the downstream phospho-Erk1/2 in endothelial cells when they were treated with VEGF-A. These findings indicate that signaling mediated via VEGFR-3 activation by its cognate ligands (VEGF-C/-D) is not required for angiogenesis, and that VEGFR-3 may play a role in this process by modulating VEGFR-2-mediated signals. © 2010 IBCB, SIBS, CAS All rights reserved.

Cite

CITATION STYLE

APA

Zhang, L., Zhou, F., Han, W., Shen, B., Luo, J., Shibuya, M., & He, Y. (2010). VEGFR-3 ligand-binding and kinase activity are required for lymphangiogenesis but not for angiogenesis. Cell Research, 20(12), 1319–1331. https://doi.org/10.1038/cr.2010.116

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free