Nuclear localisation of cytosolic phospholipase A2-alpha in the EA.hy.926 XXXX endothelial cell line is proliferation dependent and modulated by phosphorylation.

@entity1 @entity5 @entity1426 @entity866 @entity3901 @entity460 @entity1435 @entity18398 @entity18421 @entity3903
Cytosolic phospholipase A(2)-alpha ( @entity3901 ) is a @entity460 -sensitive enzyme involved in receptor-mediated eicosanoid production. In resting cells, @entity3901 is present in the cytosol and nucleus and translocates to membranes via its @entity460 -dependent lipid-binding (CaLB) domain following stimulation. @entity3901 is also regulated by phosphorylation on several residues, which results in enhanced @entity1426 release. Little is known about the factors controlling the nuclear localisation of @entity3901 . Here the nuclear localisation of @entity3901 in the EA.hy.926 @entity1 endothelial cell line was investigated. Nuclear localisation was dependent on proliferation, with subconfluent cells containing higher levels of nuclear @entity3901 than contact-inhibited confluent or serum-starved cells. The broad-range protein kinase inhibitor @entity866 caused a decrease in the nuclear level of @entity3901 , whereas the protein phosphatase inhibitor @entity18398 increased the level of nuclear @entity3901 . Using inhibitors for specific mitogen-activated protein (MAP) kinases, both @entity3903 /44(MAPK) and @entity1435 (MAPK) were shown to be important in modulating nuclear localisation. Finally, inhibition of nuclear import and export using Agaricus bisporus lectin and @entity18421 , respectively, demonstrated that @entity3901 contains functional nuclear localisation and export signals. Thus we have identified a novel mode of regulation of @entity3901 . This, together with the increasing body of evidence supporting the role of nuclear lipid second messengers in gene expression and proliferation, may have important implications for controlling the growth of endothelial cells in angiogenesis and @entity5 progression.
