TY - JOUR
AU - Ahmed, Asif
AB - VEGF-A activity is tightly regulated by ligand and receptor availability. Here we investigate the physiological function of heterodimers between VEGF receptor-1 (VEGFR-1; Flt-1) and VEGFR-2 (KDR; Flk-1) (VEGFR1−2) in endothelial cells with a synthetic ligand that binds specifically to VEGFR1−2. The dimeric ligand comprises one VEGFR-2-specific monomer (VEGF-E) and a VEGFR-1-specific monomer (PlGF-1). Here we show that VEGFR1−2 activation mediates VEGFR phosphorylation, endothelial cell migration, sustained in vitro tube formation and vasorelaxation via the nitric oxide pathway. VEGFR1−2 activation does not mediate proliferation or elicit endothelial tissue factor production, confirming that these functions are controlled by VEGFR-2 homodimers. We further demonstrate that activation of VEGFR1−2 inhibits VEGF-A-induced prostacyclin release, phosphorylation of ERK1/2 MAP kinase and mobilization of intracellular calcium from primary endothelial cells. These findings indicate that VEGFR-1 subunits modulate VEGF activity predominantly by forming heterodimer receptors with VEGFR-2 subunits and such heterodimers regulate endothelial cell homeostasis.
TI - The role of heterodimerization between VEGFR-1 and VEGFR-2 in the regulation of endothelial cell homeostasis
JF - Nature Communications
DO - 10.1038/ncomms1977
DA - 2012-07-24
UR - https://www.deepdyve.com/lp/springer-journals/the-role-of-heterodimerization-between-vegfr-1-and-vegfr-2-in-the-WHjBptJNbo
SP - 1
EP - 12
VL - 3
IS - 1
DP - DeepDyve
ER -