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.
Department of Allergy and Immunology, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo, 156-8506, Japan.
Kazuko
K
Yamaoka
Osamu
O
Kaminuma
Noriko
N
Kitamura
Akio
A
Mori
Hideki
H
Tatsumi
Soichi
S
Nemoto
Takachika
T
Hiroi
D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics*; D007376:Interleukin-2 / Q000494:pharmacology*; D053646:Interleukin-2 Receptor beta Subunit / Q000378:metabolism; D015848:Interleukin-5 / Q000235:genetics*; D010750:Phosphoproteins / Q000378:metabolism; D054645:Protein Phosphatase 1 / Q000378:metabolism*
D016207:Cytokines; D018793:Interleukin-13; D007376:Interleukin-2; D053646:Interleukin-2 Receptor beta Subunit; D015848:Interleukin-5; D010750:Phosphoproteins; D054645:Protein Phosphatase 1