Dephosphorylation of the catenins p120 and p100 in endothelial cells in response to inflammatory stimuli

Inflammatory mediators such as histamine and thrombin increase the tight-ju nction permeability of endothelial cells. Tight-junction permeability may b e independently controlled, but is dependent on the adherens junction, wher e adhesion is achieved through homotypic interaction of cadherins, which in turn are associated with cytoplasmic proteins, the catenins. p120, also te rmed p120(cas)/p120(etn), and its splice variant, p100, are catenins. p120, originally discovered as a substrate of the tyrosine kinase Src, is also a target for a protein kinase C-stimulated pathway in epithelial cells, caus ing its serine/threonine dephosphorylation. The present study shows that ph armacological activation of protein kinase C stimulated a similar pathway i n endothelial cells. Activation of receptors for agents such as histamine ( H-1), thrombin and lysophosphatidic acid in the endothelial cells also caus ed serine/threonine dephosphorylation of p120 and p100, suggesting physiolo gical relevance. However, protein kinase C inhibitors, although blocking th e effect of pharmacological activation of protein kinase C, did not block t he effects due to receptor activation. Calcium mobilization and the myosin- light-chain-kinase pathway do not participate in p120/p100 signalling. In c onclusion, endothelial cells possess protein kinase C-dependent and -indepe ndent pathways regulating p120/p100 serine/threonine phosphorylation. These data describe a new connection between inflammatory agents, receptor-stimu lated signalling and pathways potentially influencing intercellular adhesio n in endothelial cells.