PECAM-1 (CD31) functions as a reservoir for and a modulator of tyrosine-phosphorylated beta-catenin

Catenins function as regulators of cellular signaling events in addition to their previously documented roles in adherens junction formation and funct ion. Evidence to date suggests that beta and gamma catenins can act as sign aling molecules, bind transcriptional factors and translocate to the nucleu s, beta- and gamma-catenin are also major substrates for protein tyrosine k inases, and tyrosine phosphorylation of junctional proteins is correlated w ith decreased adhesiveness. One way in which catenin functions are modulate d is by dynamic incorporation into junctional complexes which controls, in part, the cytoplasmic levels of catenins, Here we show that: (1) vascular e ndothelial growth factor (VEGF) induces beta-catenin tyrosine phosphorylati on in a time-, and dose-dependent manner and that VEGF receptors co-localiz e to areas of endothelial cell-cell contact in vitro and in vivo. (2) Plate let-endothelial cell adhesion molecule (PECAM)-1 can function as a reservoi r for, and modulator of, tyrosine phosphorylated beta-catenin. (3) PECAM-1 can prevent beta-catenin nuclear translocation in transfected SW480 colon c arcinoma cells, We suggest that PECAM-1 may play a role in modulating beta- catenin tyrosine phosphorylation levels, localization and signaling and by doing so, functions as an important modulator of the endothelium.