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Selective down‐regulation of IL‐2‐mediated cytokine expression in human T cells by protein phosphatase 1 inhibitors (LB217)
Author(s) -
Kaminuma Osamu,
Kitamura Noriko,
Mori Akio,
Hiroi Takachika
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.lb217
Subject(s) - phosphorylation , microbiology and biotechnology , cytokine , protein phosphatase 2 , phosphatase , t cell receptor , dephosphorylation , biology , protein phosphatase 1 , signal transduction , t cell , intracellular , receptor , biochemistry , immune system , immunology
Protein phosphatase 1 (PP1) represents a major family of serine/threonine protein phosphatase involved in a variety of cellular events. Activation of PP1 is also regulated by its own phosphorylation/dephosphorylation as well as through interaction with its regulatory subunits. In the process of searching for IL‐2‐mediated signaling molecules in T cells by a proteomic approach, we discovered that PP1 was phosphorylated in an IL‐2 receptor (IL‐2R) β‐dependent manner. IL‐2Rβ signaling was crucial for the production of several Th2 cytokines in T cells, especially of human origin, even if it was evoked by T cell receptor (TCR) stimulation. Therefore, the role of PP1 in IL‐2‐mediated cytokine expression in human T cells was investigated by employing intracellular and low‐molecular weight PP1 inhibitors. Stimulation with IL‐2 directly induced expression of IL‐5 as well as IL‐13 in human peripheral CD4+ T cells. The expression of these cytokines evoked by IL‐2 but not by TCR stimulator was suppressed by treatment with tautomycin, a PP1 inhibitor, but not by ocadaic acid, a PP2A inhibitor. Overexpression of PP1 regulatory subunit 2, an endogenous inhibitor of PP1, also diminished IL‐2‐mediated cytokine expression in T cells. In conclusion, PP1, phosphorylated in IL‐2Rβ signaling, may play an important role in IL‐2‐mediated cytokine synthesis in human T cells.