Mj. Ratcliffe et al., Dephosphorylation of the catenins p120 and p100 in endothelial cells in response to inflammatory stimuli, BIOCHEM J, 338, 1999, pp. 471-478
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.