Letter | Published:

Role of the inositol phosphatase SHIP in negative regulation of the immune system by the receptor FeγRIIB

Nature volume 383, pages 263266 (19 September 1996) | Download Citation

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Abstract

IMMUNE complexes are potent activators of inflammatory cells, triggering effector responses through the crosslinking of Fc receptors (FcRs) such as FcΣRI or FcγRIII (ref. 1). On B cells and mast cells, immune complexes are also negative regulators of activation triggered by antigen and Fc receptors, a consequence of coligation of the B-cell antigen receptor or FcΣRI, respectively, and the inhibitory receptor FcγRIIB. Here we show that inhibitory signalling by FcγRIIB does not require the SH2-domain-containing protein tyrosine phosphatase, SHP-1, in mast cells and results in the recruitment of the SH2-domain-containing inositol polyphosphate 5-phosphatase, SHIP, to the tyrosine-phosphorylated 13-amino-acid inhibitory motif of FcγRIIB in both B cells and mast cells. SHIP, by hydrolysing the 5-phosphate of phosphatidylinositol(3,4,5)P3 and inositol(l,3,4,5)P4, suggests a mechanism by which FcγRIIB can inhibit calcium influx and downstream responses triggered by immune receptors.

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Author information

Author notes

    • Masao Ono
    • , Silvia Bolland
    •  & Jeffrey V. Ravetch

    Present address: The Rockefeller University 1230 York Avenue, New York, New York 10021, USA.

Affiliations

  1. Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA

    • Masao Ono
    • , Silvia Bolland
    • , Paul Tempst
    •  & Jeffrey V. Ravetch

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DOI

https://doi.org/10.1038/383263a0

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