SHP2 association with VE-cadherin complexes in human endothelial cells is regulated by thrombin.

Thrombin-mediated changes in endothelial cell adherens junctions modulate vascular permeability. We demonstrate that the nonreceptor protein-tyrosine phosphatase SHP2 co-precipitates with VE-cadherin complexes in confluent, quiescent human umbilical vein endothelial cells. Ligand-binding blots using a SHP2-glutathione S-transferase fusion peptide established that SHP2 associates selectively with beta-catenin in VE-cadherin complexes. Thrombin treatment ...
of human umbilical vein endothelial cells promotes SHP2 tyrosine phosphorylation and dissociation from VE-cadherin complexes. The loss of SHP2 from the cadherin complexes correlates with a dramatic increase in the tyrosine phosphorylation of beta-catenin, gamma-catenin, and p120-catenin complexed with VE-cadherin. We propose that thrombin regulates the tyrosine phosphorylation of VE-cadherin-associated beta-catenin, gamma-catenin, and p120-catenin by modulating the quantity of SHP2 associated with VE-cadherin complexes. Such changes in adherens junction complex composition likely underlie thrombin-elicited alterations in endothelial monolayer permeability.
Mesh Terms:
Antigens, CD, Cadherins, Cytoskeletal Proteins, Endothelium, Vascular, Hemostatics, Humans, Immunoblotting, Intracellular Signaling Peptides and Proteins, Ligands, Phosphorylation, Precipitin Tests, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Protein Tyrosine Phosphatases, Recombinant Fusion Proteins, Thrombin, Time Factors, Trans-Activators, Umbilical Veins, beta Catenin
J. Biol. Chem.
Date: Feb. 25, 2000
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