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Flt-1 lacking the tyrosine kinase domain is sufficient for normal development and angiogenesis in mice
Open accessAbstract
Receptor tyrosine kinases Flt-1 and Flk-1/KDR, and their ligand, the vascular endothelial growth factor (VEGF), were shown to be essential for angiogenesis in the mouse embryo by gene targeting. Flk-1/KDR null mutant mice exhibited impaired endothelial and hematopoietic cell development. On the other hand, Flt-1 null mutation resulted in early embryonic death at embryonic day 8.5, showing disorganization of blood vessels, such as overgrowth of endothelial cells. Flt-1 differs from Flk-1 in that it displays a higher affinity for VEGF but lower kinase activity, suggesting the importance of its extracellular domain. To examine the biological role of Flt-1 in embryonic development and vascular formation, we deleted the kinase domain without affecting the ligand binding region. Flt-1 tyrosine kinase-deficient homozygous mice ( flt-1 TK−/− ) developed normal vessels and survived. However, VEGF-induced macrophage migration was strongly suppressed in flt-1 TK−/− mice. These results indicate that Flt-1 without tyrosine kinase domain is sufficient to allow embryonic development with normal angiogenesis, and that a receptor tyrosine kinase plays a main biological role as a ligand-binding molecule.
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Metadata
- Authors
- Hiratsuka, S., Minowa, O., Kuno, J., Noda, T., & Shibuya, M.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1998-08-04
- Volume
- 95
- Issue
- 16
- Pages
- 9349-9354
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2084947524
- Cited by
- 1,062
- References
- 4
- FWCI
- 15.19
- Type
- journal article
- Language
- en
- Open access
- green
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