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Wessel, F., Winderlich, M., Holm, M., Frye, M., Rivera-Galdos, R., Vockel, M., Linnepe, R., Ipe, U., Stadtmann, A., Zarbock, A., Nottebaum, A.F. and Vestweber, D. (2014) Leukocyte Extravasation and Vascular Permeability Are each Controlled in Vivo by Different Tyrosine Residues of VE-Cadherin. Nature Immunology, 15, 223-230.
http://dx.doi.org/10.1038/ni.2824

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.