Purinergic regulation of vascular endothelial growth factor signaling in angiogenesis
AUTOR(ES)
Rumjahn, S M
FONTE
Nature Publishing Group
RESUMO
P2Y purine nucleotide receptors (P2YRs) promote endothelial cell tubulogenesis through breast cancer cell-secreted nucleoside diphosphate kinase (NDPK). We tested the hypothesis that activated P2Y1 receptors transactivate vascular endothelial growth factor receptor (VEGFR-2) in angiogenic signaling. P2Y1R stimulation (10 μM 2-methyl-thio-ATP (2MS-ATP)) of angiogenesis is suppressed by the VEGFR-2 tyrosine kinase inhibitor, SU1498 (1 μM). Phosphorylation of VEGFR-2 by 0.0262 or 2.62 nM VEGF was comparable with 0.01 or 10 μM 2MS-ATP stimulation of the P2Y1R. 2MS-ATP, and VEGF stimulation increased tyrosine phosphorylation at tyr1175. 2MS-ATP (0.1–10 μM) also stimulated EC tubulogenesis in a dose-dependent manner. The addition of sub-maximal VEGF (70 pM) in the presence of increasing concentrations of 2MS-ATP yielded additive effects at 2MS-ATP concentrations <3 μM, whereas producing saturated and less than additive effects at ⩾3 μM. We propose that the VEGF receptor can be activated in the absence of VEGF, and that the P2YR–VEGFR2 interaction and resulting signal transduction is a critical determinant of vascular homoeostasis and tumour-mediated angiogenesis.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2694426Documentos Relacionados
- Phosphatidylinositol 3-kinase signaling mediates angiogenesis and expression of vascular endothelial growth factor in endothelial cells
- Vascular endothelial growth factor C induces angiogenesis in vivo
- Regulation of vascular endothelial growth factor production and angiogenesis by the cytoplasmic tail of tissue factor
- Predominant role of endothelial nitric oxide synthase in vascular endothelial growth factor-induced angiogenesis and vascular permeability
- Tumor vascular permeability factor stimulates endothelial cell growth and angiogenesis.