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Chen, J., Shao, C., Lu, W., Yan, C., Yao, Q., Zhu, M., Chen, P., Gu, P., Fu, Y. and Fan, X. (2014) Adenosine Triphosphate-Induced Rabbit Corneal Endothelial Cell Proliferation in Vitro via the P2Y2-PI3K/Akt Signaling Axis. Cells, Tissues, Organs, 199, 131-139.
http://dx.doi.org/10.1159/000365654

has been cited by the following article:

• TITLE: The P2Y2 Receptor Interacts with VE-Cadherin and VEGF Receptor-2 to Regulate Rac1 Activity in Endothelial Cells

  AUTHORS: Zhongji Liao, Chen Cao, Jianjie Wang, Virginia H. Huxley, Olga Baker, Gary A. Weisman, Laurie Erb

  KEYWORDS: VE-Cadherin, P2Y Receptors, Rac, Endothelium, Adherens Junctions

  JOURNAL NAME: Journal of Biomedical Science and Engineering, Vol.7 No.14, December 31, 2014

  ABSTRACT: Vascular endothelial cadherin (VE-cadherin) mediates homophylic adhesion between endothelial cells and is an important regulator of angiogenesis, blood vessel permeability and leukocyte trafficking. Rac1, a member of the Rho family of GTPases, controls VE-cadherin adhesion by acting downstream of several growth factors, including angiopoietin-1 and vascular endothelial growth factor (VEGF). Here we show that UTP-induced activation of the Gq protein-coupled P2Y2 nucleotide receptor (P2Y2R) in human coronary artery endothelial cells (HCAECs) activated Rac1 and caused a transient complex to form between P2Y2R, VE-cadherin and VEGF receptor-2 (VEGFR-2). Knockdown of VE-cadherin expression with siRNA did not affect UTP-induced activation of extracellular signal-regulated kinases 1/2 (ERK1/2) but led to a loss of UTP-induced Rac1 activation and tyrosine phosphorylation of p120 catenin, a cytoplasmic protein known to interact with VE- cadherin. Activation of the P2Y2R by UTP also caused a prolonged interaction between p120 catenin and vav2 (a guanine nucleotide exchange factor for Rac) that correlated with the kinetics of UTP-induced tyrosine phosphorylation of p120 catenin and VE-cadherin. Inhibitors of VEGFR-2 (SU1498) or Src (PP2) significantly diminished UTP-induced Rac1 activation, tyrosine phosphorylation of p120 catenin and VE-cadherin, and association of the P2Y2R with VE-cadherin and p120 catenin with vav2. These findings suggest that the P2Y2R uses Src and VEGFR-2 to mediate association of the P2Y2R with VE-cadherin complexes in endothelial adherens junctions to activate Rac1.