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Protein kinase C‐mediated calcium entry dependent upon dihydropyridine‐sensitive channels: a T‐cell receptor‐coupled signaling pathway involved in interleukin 4 synthesis
Author(s) -
Savignac Magali,
Badou Abdallah,
Moreau Marc,
Leclerc Catherine,
Guéry Jean-Charles,
Paulet Pierre,
Druet Philippe,
Ragab-Thomas Jeannie,
Pelletier Lucette
Publication year - 2001
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/fj.00-0733fje
Subject(s) - chemistry , microbiology and biotechnology , signal transduction , dihydropyridine , protein kinase c , receptor , protein kinase a , interleukin 1 receptor , calcium , kinase , biochemistry , interleukin , biology , cytokine , immunology , organic chemistry
Signaling events induced by T‐cell receptor (TCR) engagement involve a cascade of tyrosine phosphorylation events leading to activation of several downstream pathways and resulting in cytokine production. TCR‐dependent interferon γ (IFN‐γ) production by Th1 cells has been shown to require tyrosine phosphorylation of numerous proteins, intracellular Ca 2 + mobilization, and mitogen‐activated protein kinase activation. In contrast, the signaling pathways responsible for TCR‐dependent interleukin (IL) 4 production remain poorly understood. By using a T‐cell hybridoma that displays a hierarchized production of IL‐4 and IFN‐γ following TCR engagement (IL‐4 being produced at a lower threshold of activation than IFN‐γ), we showed that IL‐4 can be produced in spite of the absence of tyrosine phosphorylation of phospholipase Cγ1. However, protein kinase C (PKC) was found to be translocated to the cell membrane, and an increase in intracellular Ca 2 + concentration was observed. The PKC‐dependent Ca 2 + response and IL‐4 expression were accounted for by a dihydropyridine‐sensitive Ca 2 + entry, which could occur through L‐type calcium channels. This pathway was also functional in the D10G4.1 Th2 clone. The fact that this pathway, allowing IL‐4 production, did not require optimal activation might explain why low doses of peptides or altered peptide ligands favor Th2 responses.