Biliary glycoprotein (BGPa, CD66a, CEACAM1) mediates inhibitory signals
| Autor: | Ines Chen, Silvia Bolland, James Parker, Akito Maeda, Wolfgang Zimmermann, Tie Chen |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Recombinant Fusion Proteins
Immunology Mutant Biology Transfection Cell Line src Homology Domains Antigens CD Consensus sequence Immunology and Allergy Animals Humans Calcium Signaling Tyrosine Receptor Glycoproteins Receptors IgG Cell Biology Antigens Differentiation Transmembrane protein Cell biology Carcinoembryonic Antigen Protein Structure Tertiary Transmembrane domain Cytoplasm Mutagenesis Site-Directed Immunoglobulin superfamily Cell Adhesion Molecules Chickens Signal Transduction |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 0741-5400 |
| Popis: | Biliary glycoprotein (BGP, CD66a, CEACAM1) is a member of the carcinoembryonic antigen family (CEA, CD66), a group of transmembrane proteins belonging to the immunoglobulin superfamily. The structural features surrounding the tyrosine residues in the cytoplasmic domain of BGP share similarity with the consensus sequence of the immunoreceptor tyrosine-based inhibition motif (ITIM), the docking site for SHIP, SHP-1, and SHP-2 molecules. Using the well-characterized inhibitory receptor, FcγRIIB, we constructed a FcγRIIB-BGPa chimeric molecule that contained the extracellular and transmembrane domain of FcγRIIB and the cytoplasmic tail of BGPa and expressed it in DT40 B cells. Our results showed that FcγRIIB-BGPa, just like the unmodified FcγRIIB molecule, inhibited calcium influx in activated DT40 B cells. Substitution of tyrosine with phenylalanine (Y459F) in FcγRIIB-BGPa completely abrogated its ability to inhibit calcium influx, indicating that the motif surrounding Y459 is ITIM. The presence of ITIM was also supported by showing that the FcγRIIB-BGPa-mediated inhibitory effect was reduced in SHP-1and SHP-2 mutant DT40 B cells and further diminished in a SHP-1/-2 double-deficient mutant line. The results suggest that SHP-1 and SHP-2 are required for the FcγRIIB-BGPa-mediated inhibitory signals. |
| Databáze: | OpenAIRE |
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