Deletion of SHIP or SHP-1 reveals two distinct pathways for inhibitory signaling
- M Ono 1, H Okada , S Bolland , S Yanagi , T Kurosaki , J V Ravetch
- 1Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, New York 10021, USA.
- 0Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, New York 10021, USA.
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View abstract on PubMed
Summary
This summary is machine-generated.Immune inhibitory coreceptors utilize distinct phosphatases, SHP-1 (SH2-containing inositol phosphatase 1) or SHIP (SH2-containing inositol phosphatase), for signaling. This selective recruitment dictates outcomes in B cell receptor-triggered apoptosis.
Area Of Science
- Immunology
- Cell Signaling
- Molecular Biology
Background
- Inhibitory coreceptors modulate immune receptor activation.
- Inositol polyphosphate 5'-phosphatase (SHIP) and tyrosine phosphatase SHP-1 are key signaling molecules.
- Their specific roles in inhibitory signaling pathways remain to be fully elucidated.
Purpose Of The Study
- To investigate the necessity, interaction, and redundancy of SHIP and SHP-1 in immune inhibitory signaling.
- To define distinct classes of inhibitory responses mediated by these phosphatases.
- To understand their impact on B cell receptor (BCR)-triggered apoptosis.
Main Methods
- Generation of SHP-1-deficient and SHIP-deficient B cell lines.
- Assessment of inhibitory signaling capabilities in these cell lines.
- Analysis of BCR-triggered apoptosis in response to receptor engagement.
Main Results
- Two distinct classes of inhibitory responses were identified, selectively recruiting either SHP-1 or SHIP.
- Fc gammaRIIB-mediated inhibitory signaling requires SHIP, not SHP-1.
- KIR-mediated inhibitory signaling requires SHP-1, not SHIP.
- SHP-1 signaling blocks apoptosis, while SHIP signaling attenuates proapoptotic signals initiated by Fc gammaRIIB.
Conclusions
- SHIP and SHP-1 play distinct and non-redundant roles in mediating inhibitory coreceptor signaling.
- Selective recruitment of these phosphatases dictates the cellular outcome, specifically in BCR-triggered apoptosis.
- This selective recruitment provides a mechanism for fine-tuning immune responses.
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