Protein phosphatases 1 and 2A maintain endothelial cells in a resting state, limiting the motility that is needed for the morphogenic process of angiogenesis

Angiogenesis that is induced by cancers, including those of the head and ne ck, requires endothelial cells to shift from a nonmotile resting state to a n increased level of motility. Using a human microvascular endothelial cell line, this study shows the importance of the serine/threonine protein phos phatases 1 (PP1) and 2A (PP2A) in restricting endothelial cell motility. Tr eatment of endothelial cells with increasing concentrations of the PP1 and PP2A inhibitor okadaic acid resulted in cell rounding and increased motilit y, which was accompanied by cytoskeletal disorganization involving a loss o f filamentous beta-tubulin and F-actin. These effects occurred at okadaic a cid levels that selectively inhibit PP2A and became more prominent with hig her levels that inhibit both PP2A and PP1. This study shows the importance of PP1 and PP2A in maintaining cytoskeletal organization, thereby limiting endothelial cell motility, and suggests that pharmacologic approaches to en hance PP1 and PP2A activities may be useful in preventing key events of the angiogenic process.