VEGFR3 Extracellular Domain (human, recombinant)

VEGFR3 is a receptor tyrosine kinase that is composed of an N-terminal extracellular ligand-binding domain, which contains seven immunoglobulin-like (Ig-like) domains, a transmembrane domain, and an intracellular tyrosine kinase domain, which is subject to phosphorylation and contains a kinase insert domain and the C-terminal domain.^1,2 It contains an N-terminal signal peptide cleavage site at Tyr²⁵ and can also be cleaved between Arg⁴⁷² and Ser⁴⁷³ creating an alternate N-terminus.^3,4 VEGFR3 forms homodimers or heterodimers with VEGFR2, with heterodimerization inducing changes in VEGFR3 autophosphorylation patterns.² It is expressed in lymphatic endothelial cells, where it is bound by the growth factors VEGF-C or VEGF-D and involved in cell proliferation, migration, and survival, as well as in cells undergoing angiogenesis or lymphangiogenesis, and in osteoblasts, neuronal progenitor cells, and macrophages.^2,1 Inactivating mutations in VEGFR3 have been found in patients with hereditary lymphedema.^5,6 Activation of VEGFR3 signaling increases tumor growth in a mouse orthotopic model of colorectal cancer, and VEGFR3 protein levels are increased in tumor tissue and tumor-associated macrophages isolated from patients with non-metastatic colorectal cancer.⁷ Cayman's VEGFR3 Extracellular Domain (human, recombinant) protein can be used for enzyme activity assays. This protein consists of 763 amino acids, has a calculated molecular weight of 86 kDa, and a predicted N-terminus of Tyr²⁵ after signal peptide cleavage. By SDS-PAGE, under non-reducing conditions, the apparent molecular mass of the protein is approximately 130 kDa due to glycosylation.

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1. Park, S.A., Jeon, M.S., Ha, K.-T., et al. Structure and function of vascular endothelial growth factor and its receptor system. BMB Rep. 51(2), 73-78 (2018).

2. Koch, S., and Claesson-Welsh, L. Signal transduction by vascular endothelial growth factor receptors. Cold Spring Harb. Perspect. Med. 2(7), a006502 (2012).

3. Lee, J., Gray, A., Yuan, J., et al. Vascular endothelial growth factor-related protein: A ligand and specific activator of the tyrosine kinase receptor Flt4. Proc. Natl. Acad. Sci. USA 93(5), 1988-1992 (1996).

4. Leppänen, V.-M., Tvorogov, D., Kisko, K., et al. Structural and mechanistic insights into VEGF receptor 3 ligand binding and activation. Proc. Natl. Acad. Sci. USA 110(32), 12960-12965 (2013).

5. Irrthum, A., Karkkainen, M.J., Devriendt, K., et al. Congenital hereditary lymphedema caused by a mutation that inactivates VEGFR3 tyrosine kinase. Am. J. Hum. Genet. 67(2), 295-301 (2000).

6. Gordon, K., Spiden, S.L., Connell, F.C., et al. FLT4/VEGFR3 and Milroy disease: Novel mutations, a review of published variants and database update. Hum. Mutat. 34(1), 23-31 (2013).

7. Tacconi, C., Ungaro, F., Correale, C., et al. Activation of the VEGFC/VEGFR3 pathway induces tumor immune escape in colorectal cancer. Cancer Res. 79(16), 4196-4210 (2019).