Anti-Phospho-VEGFR3: Rabbit VEGFR3, Phospho-Tyr1230/1231 Antibody

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

REFERENCES  

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

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*Optimal working dilutions must be determined by end user.

• Product Sheet CY1115