P2y receptor-mediated angiogenesis via vascular endothelial growth factor receptor 2 signaling.
Pathological as well as physiological angiogenesis is known to be regulated by such factors as nucleotides and Vascular Endothelial Growth Factor (VEGF). Activated P2Y nucleotide receptors have been observed to associate and transactivate VEGF Receptor 2 (VEGFR2), suggesting a cooperation between nucleotide and VEGF signaling in angiogenesis. P2YR mediated VEGFR2 signaling therefore may be important in describing the angiogenic signaling of nucleotides such as ATP. Here, we provide evidence that supports the notion of P2YR-VEGFR2 signaling. The significant angiogenic effect of P2Y1/2 receptor agonists (100 microM ATP and 10 microM 2MS-ATP) on endothelial cell tubulogenesis was suppressed back to near control levels upon addition of 1 microM SU1498 (specific VEGFR2 tyrosine kinase inhibitor). We believe that this P2YR-VEFGR2 signaling is an important component of pathological, as well as physiological angiogenesis.
Rumjahn
Sharif M
SM
Department of Pharmacology, University of Nevada School of Medicine, Reno, Nevada, USA. rumjahn@unr.edu
Baldwin
Karla A
KA
Buxton
Iain L O
IL
D000255:Adenosine Triphosphate / Q000494:pharmacology; D002478:Cells, Cultured; D002934:Cinnamates / Q000494:pharmacology; D006801:Humans; D018919:Neovascularization, Physiologic / Q000502:physiology*; D009701:Nucleoside-Diphosphate Kinase / Q000502:physiology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000502:physiology*; D058473:Receptors, Purinergic P2Y2; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors / Q000502:physiology*
D002934:Cinnamates; C546385:P2RY2 protein, human; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D018048:Receptors, Purinergic P2; D058473:Receptors, Purinergic P2Y2; C483044:SU 1498; D000255:Adenosine Triphosphate; D040301:Vascular Endothelial Growth Factor Receptor-2; C121988:nucleoside diphosphate kinase 2; D009701:Nucleoside-Diphosphate Kinase