Alternative titles; symbols
HGNC Approved Gene Symbol: VEGFD
Cytogenetic location: Xp22.2 Genomic coordinates (GRCh38): X:15,345,596-15,384,413 (from NCBI)
Vascular endothelial growth factors (VEGFs) are modulators of endothelial cell growth and function (summary by Yamada et al., 1997).
Yamada et al. (1997) identified a human EST sequence with homology to the C-terminal region of VEGFC (601528). They assembled a full-length cDNA sequence from a combination of overlapping EST sequences and RACE PCR products. The resulting cDNA sequence predicted a protein of 354 amino acids that was 23% identical to VEGFC. Northern blot analysis showed that the gene, which the authors symbolized VEGFD, was expressed as a 2.2-kb transcript with highest expression in lung, heart, small intestine, and fetal lung, and lower levels in skeletal muscle, colon, and pancreas.
By computer-based homology searching, Achen et al. (1998) identified a member of the VEGF family and designated it VEGFD. VEGFD was most closely related to VEGFC by virtue of the presence of N- and C-terminal extensions that were not found in other VEGF family members. In adult human tissues, VEGFD mRNA was most abundant in heart, lung, skeletal muscle, colon, and small intestine.
Achen et al. (1998) analyzed VEGFD receptor specificity and found that VEGFD is a ligand for VEGFR2 (FLK1; 191306) and VEGFR3 (FLT4; 136352); furthermore, VEGFD activates these receptors. VEGFD did not bind to VEGFR1. Expression of a truncated derivative of VEGFD demonstrated that the receptor-binding capacities reside in the portion of the molecule that is most closely related in primary structure to other VEGF family members and that corresponds to the mature form of VEGFC. In addition, VEGFD is a mitogen for endothelial cells. The structural and functional similarities between VEGFD and VEGFC defined a subfamily of the VEGFs.
Yamada et al. (1997) used PCR mapping panels to map VEGFD to chromosome Xp22.31. They noted that the gene is located on cosmid HSU69570 and is linked to the sequence tagged site SGC34929.
Using a mouse tumor model, Stacker et al. (2001) showed that VEGFD can induce tumor angiogenesis through VEGFR2 and tumor lymphangiogenesis through VEGFR3, whereas VEGF, which does not activate VEGFR3, induces only tumor angiogenesis. Immunohistochemistry demonstrated that cell lines expressing VEGFD established tumors in immunodeficient mice in lymphatic vessels, as defined by expression of LYVE1 (605702) and by the lymphatic-specific patent blue V dye. In contrast, cell lines expressing VEGF did not establish tumors in lymphatic vessels. An antibody to the VEGFR2/VEGFR3-binding region of VEGFD blocked tumor growth.
Achen, M. G., Jeltsch, M., Kukk, E., Makinen, T., Vitali, A., Wilks, A. F., Alitalo, K., Stacker, S. A. Vascular endothelial growth factor D (VEGF-D) is a ligand for the tyrosine kinases VEGF receptor 2 (Flk1) and VEGF receptor 3 (Flt4). Proc. Nat. Acad. Sci. 95: 548-553, 1998. [PubMed: 9435229] [Full Text: https://doi.org/10.1073/pnas.95.2.548]
Stacker, S. A., Caesar, C., Baldwin, M. E., Thornton, G. E., Williams, R. A., Prevo, R., Jackson, D. G., Nishikawa, S., Kubo, H., Achen, M. G. VEGF-D promotes the metastatic spread of tumor cells via the lymphatics. Nature Med. 7: 186-191, 2001. [PubMed: 11175849] [Full Text: https://doi.org/10.1038/84635]
Yamada, Y., Nezu, J., Shimane, M., Hirata, Y. Molecular cloning of a novel vascular endothelial growth factor, VEGF-D. Genomics 42: 483-488, 1997. [PubMed: 9205122] [Full Text: https://doi.org/10.1006/geno.1997.4774]