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Protein phosphatase 1 is involved in IL ‐2‐induced IL ‐5 and IL ‐13 expression in human T cells
Author(s) -
Yamaoka Kazuko,
Kaminuma Osamu,
Kitamura Noriko,
Mori Akio,
Tatsumi Hideki,
Nemoto Soichi,
Hiroi Takachika
Publication year - 2012
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/j.1365-2443.2012.01610.x
Subject(s) - biology , microbiology and biotechnology , cytokine , protein tyrosine phosphatase , interleukin 2 , phosphatase , phosphorylation , tyrosine phosphorylation , t cell , transfection , cell culture , immune system , immunology , genetics
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 FK 506‐binding protein 4 were identified. Particularly, PP 1β augmented IL ‐5 and IL ‐13 expression stimulated by IL ‐2 but not by anti‐ CD 3 antibody in human peripheral CD 4 + T cells upon ectopic expression. IL ‐2‐induced cytokine expression was suppressed by overexpression of PP 1 regulatory subunit 2. A PP 1 inhibitor, tautomycin, but not a PP 2A inhibitor, okadaic acid, also inhibited the IL ‐2R‐mediated responses. It was conclusively shown that PP 1 is crucially involved in IL ‐2‐mediated IL ‐5 and IL ‐13 synthesis in human T cells.