IMMUNE complexes are potent activators of inflammatory cells, triggering effector responses through the crosslinking of Fc receptors (FcRs) such as FcεRI 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 FcεRI, 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(1,3,4,5)P4, suggests a mechanism by which FcγRIIB can inhibit calcium influx and downstream responses triggered by immune receptors.
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