Protein phosphatase 1 is involved in IL-2-induced IL-5 and IL-13 expression in human T cells.

IL-2 plays an important role in immunological and other biological functions. This cytokine directly induces the production of several cytokines, such as IL-5 and IL-13. The mechanisms of IL-2-mediated cytokine synthesis are mostly unclear; however, the involvement of IL-2 receptor (IL-2R)β has been suggested. In this study, the signaling molecule downstream of IL-2Rβ was investigated, employing a proteomic approach. Full-length IL-2Rβ and its mutant in which the intracellular component was truncated were introduced in an IL-2Rα- and IL-2Rγ-stably transfected T cell hybridoma, S1. The differential phosphorylation profiles of protein tyrosine residues in these cells upon IL-2 stimulation were examined by two-dimensional gel electrophoresis. The candidate phosphoproteins of interest were re-covered, in-gel digested and mass spectrometry fingerprinted. Among proteins specifically phosphorylated in full-length IL-2Rβ-expressing cells in response to IL-2 stimulation, protein phosphatase (PP)1β and FK506-binding protein 4 were identified. Particularly, PP1β augmented IL-5 and IL-13 expression stimulated by IL-2 but not by anti-CD3 antibody in human peripheral CD4+ T cells upon ectopic expression. IL-2-induced cytokine expression was suppressed by overexpression of PP1 regulatory subunit 2. A PP1 inhibitor, tautomycin, but not a PP2A inhibitor, okadaic acid, also inhibited the IL-2R-mediated responses. It was conclusively shown that PP1 is crucially involved in IL-2-mediated IL-5 and IL-13 synthesis in human T cells.