PROTEIN PHOSPHATASE 2A PLAYS A CRITICAL ROLE IN INTERLEUKIN-2-INDUCEDBETA(2)-INTEGRIN DEPENDENT HOMOTYPIC ADHESION IN HUMAN CD4(-CELL LINES() T)

Besides its function as a growth factor for T lymphocytes, interleukin 2 (IL-2) induces beta(2)-integrin mediated adhesion, migration, and e xtravasation of T lymphocytes. It is, however, largely unknown how IL- 2 receptors (IL-2R) are coupled to the beta(2)-integrin adhesion pathw ay. Because IL-2 modulates enzymatic activity and/or subcellular distr ibution of serine/threonine phosphatases 1 and 2A (PP1/PP2A) in T cell s, we examined the role of these phosphatases in IL-2 induced homotypi c adhesion in antigen specific human CD4(+) T cell lines. We show that calyculin A, a potent inhibitor of PP1 and PP2A, blocks PP1/PP2A acti vity and IL-2 induced adhesion, whereas cyclosporin A, an inhibitor of protein serine/threonine phosphatase 2B (PP2B), does not, suggesting that PP1 and/or PP2A are involved in IL-2 induced adhesion. Endothall, which preferentially inhibits PP2A, strongly inhibited cytokine induc ed adhesion, whereas the structurally related compound 1,4-dimethylend othall had no effect on either phosphatase activity or the adhesion re sponse. Okadaic acid, which preferentially inhibits PP2A, almost compl etely blocked IL-2-induced adhesion, whereas tautomycin, a potent inhi bitor of PP1, had no inhibitory effect on cytokine induced adhesion at concentrations which strongly inhibited phosphatase activity. In conc lusion, these data provide evidence that PP2A plays a critical role in IL-2-induced beta(2)-integrin-dependent adhesion of human T cell line s. (C) 1997 Academic Press Limited.