Document Detail

Signaling through mutants of the IgA receptor CD89 and consequences for Fc receptor gamma-chain interaction.
MedLine Citation:
PMID:  16517729     Owner:  NLM     Status:  MEDLINE    
The prototypic receptor for IgA (FcalphaRI, CD89) is expressed on myeloid cells and can trigger phagocytosis, tumor cell lysis, and release of inflammatory mediators. The functions of FcalphaRI and activating receptors for IgG (FcgammaRI and FcgammaRIII) are dependent on the FcR gamma-chain dimer. This study increases our understanding of the molecular basis of the FcalphaRI-FcR gamma-chain transmembrane interaction, which is distinct from that of other activatory FcRs. FcalphaRI is unique in its interaction with the common FcR gamma-chain, because it is based on a positively charged residue at position 209, which associates with a negatively charged amino acid of FcR gamma-chain. We explored the importance of the position of this positive charge within human FcalphaRI for FcR gamma-chain association and FcalphaRI functioning with the use of site-directed mutagenesis. In an FcalphaRI R209L/A213H mutant, which represents a vertical relocation of the positive charge, proximal and distal FcR gamma-chain-dependent functions, such as calcium flux, MAPK phosphorylation, and IL-2 release, were similar to those of wild-type FcalphaRI. A lateral transfer of the positive charge, however, completely abrogated FcR gamma-chain-dependent functions in an FcalphaRI R209L/M210R mutant. By coimmunoprecipitation, we have demonstrated the loss of a physical interaction between FcR gamma-chain and FcalphaRI M210R mutant, thus explaining the loss of FcR gamma-chain-dependent functions. In conclusion, not only the presence of a basic residue in the transmembrane region of FcalphaRI, but also the orientation of FcalphaRI toward the FcR gamma-chain dimer is essential for FcR gamma-chain association. This suggests the involvement of additional amino acids in the FcalphaRI-FcR gamma-chain interaction.
Jantine E Bakema; Simone de Haij; Constance F den Hartog-Jager; Johanna Bakker; Gestur Vidarsson; Marjolein van Egmond; Jan G J van de Winkel; Jeanette H W Leusen
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  176     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  2006 Mar 
Date Detail:
Created Date:  2006-03-06     Completed Date:  2006-04-24     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3603-10     Citation Subset:  AIM; IM    
Immunotherapy Laboratory, Department of Immunology, University Medical Center Utrecht, Lundlaan 6, 3584 EA Utrecht, The Netherlands;
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MeSH Terms
Amino Acid Sequence
Antigens, CD / genetics*,  immunology,  metabolism*
Calcium / metabolism
Cell Line
Cell Membrane / metabolism
Interleukin-2 / biosynthesis
Mitogen-Activated Protein Kinases / metabolism
Molecular Sequence Data
Mutation / genetics*
Protein Binding
Receptors, Fc / genetics*,  immunology,  metabolism*
Receptors, IgG / genetics,  immunology*,  metabolism*
Sequence Alignment
Signal Transduction*
Reg. No./Substance:
0/Antigens, CD; 0/Fc(alpha) receptor; 0/Interleukin-2; 0/Ligands; 0/Receptors, Fc; 0/Receptors, IgG; 7440-70-2/Calcium; EC Protein Kinases

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