Bakema, Jantine E.;
Bakker, Annie;
de Haij, Simone;
Honing, Henk;
Bracke, Madelon;
Koenderman, Leo;
Vidarsson, Gestur;
van de Winkel, Jan G. J.;
Leusen, Jeanette H. W.
Inside-Out Regulation of FcαRI (CD89) Depends on PP2A
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Media type:
E-Article
Title:
Inside-Out Regulation of FcαRI (CD89) Depends on PP2A
Contributor:
Bakema, Jantine E.;
Bakker, Annie;
de Haij, Simone;
Honing, Henk;
Bracke, Madelon;
Koenderman, Leo;
Vidarsson, Gestur;
van de Winkel, Jan G. J.;
Leusen, Jeanette H. W.
Published:
The American Association of Immunologists, 2008
Published in:
The Journal of Immunology, 181 (2008) 6, Seite 4080-4088
Language:
English
DOI:
10.4049/jimmunol.181.6.4080
ISSN:
0022-1767;
1550-6606
Origination:
Footnote:
Description:
Abstract To achieve a correct cellular immune response toward pathogens, interaction between FcR and their ligands must be regulated. The Fc receptor for IgA, FcαRI, is pivotal for the inflammatory responses against IgA-opsonized pathogens. Cytokine-induced inside-out signaling through the intracellular FcαRI tail is important for FcαRI-IgA binding. However, the underlying molecular mechanism governing this process is not well understood. In this study, we report that PP2A can act as a molecular switch in FcαRI activation. PP2A binds to the intracellular tail of FcαRI and, upon cytokine stimulation, PP2A becomes activated. Subsequently, FcαRI is dephosphorylated on intracellular Serine 263, which we could link to receptor activation. PP2A inhibition, in contrast, decreased FcαRI ligand binding capacity in transfected cells but also in eosinophils and monocytes. Interestingly, PP2A activity was found crucial for IgA-mediated binding and phagocytosis of Neisseria meningitidis. The present findings demonstrate PP2A involvement as a molecular mechanism for FcαRI ligand binding regulation, a key step in initiating an immune response.