Inside-out regulation of Fc alpha RI (CD89) depends on PP2A

J Immunol. 2008 Sep 15;181(6):4080-8. doi: 10.4049/jimmunol.181.6.4080.


To achieve a correct cellular immune response toward pathogens, interaction between FcR and their ligands must be regulated. The Fc receptor for IgA, FcalphaRI, is pivotal for the inflammatory responses against IgA-opsonized pathogens. Cytokine-induced inside-out signaling through the intracellular FcalphaRI tail is important for FcalphaRI-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 FcalphaRI activation. PP2A binds to the intracellular tail of FcalphaRI and, upon cytokine stimulation, PP2A becomes activated. Subsequently, FcalphaRI is dephosphorylated on intracellular Serine 263, which we could link to receptor activation. PP2A inhibition, in contrast, decreased FcalphaRI 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 FcalphaRI ligand binding regulation, a key step in initiating an immune response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, CD / metabolism*
  • Cell Line
  • Cells, Cultured
  • Humans
  • Intracellular Fluid / chemistry
  • Intracellular Fluid / immunology
  • Intracellular Fluid / metabolism
  • Mice
  • Molecular Sequence Data
  • Monocytes / enzymology
  • Monocytes / immunology
  • Monocytes / metabolism
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism
  • Peptide Fragments / physiology
  • Protein Phosphatase 2 / antagonists & inhibitors
  • Protein Phosphatase 2 / metabolism
  • Protein Phosphatase 2 / physiology*
  • Protein Structure, Tertiary
  • Receptors, Fc / metabolism*
  • Signal Transduction / immunology
  • U937 Cells


  • Antigens, CD
  • Fc(alpha) receptor
  • Peptide Fragments
  • Receptors, Fc
  • PPP2CA protein, human
  • Protein Phosphatase 2