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Biliary glycoprotein (BGPa, CD66a, CEACAM1) mediates inhibitory signals
T Chen1, W Zimmermann, J Parker
1Department of Microbiology and Immunology, Department of Medicine, and Walther Oncology Center, Indiana University School of Medicine, Indianapolis 46202-5120, USA. tiechen@iupui.edu
Journal of Leukocyte Biology
|August 9, 2001
Summary
Biliary glycoprotein (BGP) contains an inhibitory motif (ITIM) in its cytoplasmic tail, which is crucial for its function. This ITIM recruits SHP-1 and SHP-2 phosphatases to inhibit B cell activation.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Biliary glycoprotein (BGP, CEACAM1) is an immunoglobulin superfamily member.
- BGP's cytoplasmic domain shares sequence similarity with inhibitory motifs.
Purpose of the Study:
- To investigate the inhibitory function of BGP's cytoplasmic tail.
- To determine if BGP contains an immunoreceptor tyrosine-based inhibition motif (ITIM).
Main Methods:
- Constructed a chimeric FcgammaRIIB-BGPa molecule in DT40 B cells.
- Utilized tyrosine-to-phenylalanine substitution (Y459F) to abrogate ITIM function.
- Assessed inhibition of calcium influx in wild-type and mutant DT40 B cells.
Main Results:
- FcgammaRIIB-BGPa inhibited calcium influx, similar to FcgammaRIIB.
- Y459F mutation abolished the inhibitory effect, confirming the ITIM.
- Inhibitory function was reduced in SHP-1 and SHP-2 deficient cells.
Conclusions:
- BGP possesses an ITIM in its cytoplasmic tail.
- SHP-1 and SHP-2 phosphatases mediate BGP's inhibitory signaling.
- BGP plays a role in regulating B cell activation.
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