BACKGROUND The Vascular Endothelial Growth Factor Receptor (VEGFR) family has three members: VEGFR-1 (also known as flt-1), VEGFR-2 (KDR/flk-1), and VEGFR-3 (FLT4). In VEGFR-3, the fifth Ig homology domain of the extracellular portion is proteolytically cleaved and the resulting polypeptides remain linked by two-disulfide bonds.1 The ligands binding to VEGFRs belong to the VEGF family of growth factors, which has five cellular members: VEGF, placenta growth factor (PlGF), VEGF-B, VEGF-C, VEGF-D, and the recently cloned viral VEGF homologue VEGF-E.2 VEGFR-3 is required for cardiovascular development during embryogenesis. In adults, this receptor is expressed in lymphatic endothelial cells. VEGF-C and VEGF-D are VEGFR3 ligands. The binding of VEGF ligands to VEGFRs activates VEGFR3 signaling, which regulates cardiovascular development, angiogenesis, and lymphangiogenesis.3 Signaling by VEGFR3 involves the CrkII, PI-3 kinase, and Grb2 pathways, leading to activation of downstream JNK1/2, Akt, and Erk1/2.4
Activation of VEGFR3 leads to phosphorylation of a number of tyrosine residues in the receptor cytoplasmic domain. Phosphorylation of Tyr1063 and 1068 on the activation loop is closely related with opening of receptor ATP-binding site. Other five tyrosines (Tyr1230, 1231, 1265, 1337 and 1363) in the C-terminal tail of VEGFR3 were shown to be phosphorylated upon ligand stimulation. However, only Tyr1230, 1231, and 1265 were phosphorylated in both VEGFR3-homodimers and VEGFR3-VEGFR2 heterodimers. Tyr1337 and Tyr1363 only can be phosphorylated in VEGFR3 homerdimers.4 Particularly Tyr1230 and 1231 were shown to be involved in lymphendothelial cell DNA synthesis, migration, and apoptosis.5
1. Otrock, Z.K. et al. : Blood Cells Mol Dis. 38:258, 2007.
2. Taipale, J. et al.: Curr Top Microbiol Immunol. 237:85, 1999.
3. Su, J.L. et al.: Br J Cancer. 96:541, 2007.
4. Bahram, F. & Claesson-Wesh, L.: Pathophysiol. 17:253-61, 2010
5. Dixelius, J. et al: J. Biol. Chem. 278:40973-9, 2003
Products are for research use only. They are not intended for human, animal, or diagnostic applications.
Raised against a short peptide from sequence surrounding and containing phosphorylated Tyr1230/1231 of human VEGFR3.
Species & predicted
reactivity ( ):
Weight of protein:
Detects phosphorylated VEGFR3 (Tyr1230/1231) proteins without cross-reactivity with other family members.
Store at -20°C, 4°C for frequent use. Avoid repeated freeze-thaw cycles.
*Optimal working dilutions must be determined by end user.