Protein phosphatase 2A plays a critical role in interleukin-2-induced beta 2-integrin dependent homotypic adhesion in human CD4+ T cell lines.
Besides its function as a growth factor for T lymphocytes, interleukin 2 (IL-2) induces beta 2-integrin mediated adhesion, migration, and extravasation of T lymphocytes. It is, however, largely unknown how IL-2 receptors (IL-2R) are coupled to the beta 2-integrin adhesion pathway. Because IL-2 modulates enzymatic activity and/or subcellular distribution of serine/threonine phosphatases 1 and 2A (PP1/PP2A) in T cells, we examined the role of these phosphatases in IL-2 induced homotypic adhesion in antigen specific human CD4+ T cell lines. We show that calyculin A, a potent inhibitor of PP1 and PP2A, blocks PP1/PP2A activity 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 induced adhesion, whereas the structurally related compound 1,4-dimethylendothall had no effect on either phosphatase activity or the adhesion response. Okadaic acid, which preferentially inhibits PP2A, almost completely blocked IL-2-induced adhesion, whereas tautomycin, a potent inhibitor of PP1, had no inhibitory effect on cytokine induced adhesion at concentrations which strongly inhibited phosphatase activity. In conclusion, these data provide evidence that PP2A plays a critical role in IL-2-induced beta 2-integrin-dependent adhesion of human T cell lines.
Brockdorff
J
J
Institute of Medical Microbiology and Immunology, University of Copenhagen, Denmark.
Nielsen
M
M
Svejgaard
A
A
Dobson
P
P
Röpke
C
C
Geisler
C
C
Odum
N
N
D018821:CD18 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002448:Cell Adhesion; D002460:Cell Line; D016213:Cyclins / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology*; D019319:Okadaic Acid / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000502:physiology*; D054648:Protein Phosphatase 2
D018821:CD18 Antigens; D016213:Cyclins; D007376:Interleukin-2; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2