ROLE OF THE INOSITOL PHOSPHATASE SHIP IN NEGATIVE REGULATION OF THE IMMUNE-SYSTEM BY THE RECEPTOR FC-GAMMA-RIIB

IMMUNE complexes are potent activators of inflammatory cells, triggeri ng effector responses through the crosslinking of Fc receptors (FcRs) such as Fc epsilon RI or Fc gamma RIII (ref, 1). On B cells and mast c ells, immune complexes are also negative regulators of activation trig gered by antigen and Fc receptors, a consequence of coligation of the B-cell antigen receptor or Fc epsilon RI, respectively, and the inhibi tory receptor Fc gamma RIIB. Here we show that inhibitory signalling b y Fc gamma RIIB does not require the SH2-domain-containing protein tyr osine phosphatase, SHP-1, in mast cells and results in the recruitment of the SH2-domain-containing inositol polyphosphate 5-phosphatase, SH IP, to the tyrosine-phosphorylated 13-amino-acid inhibitory motif of F c gamma RIIB in both B cells and mast cells. SHIP, by hydrolysing the 5-phosphate of phosphatidylinositol(3,4,5)P-3 and inositol(1,3,4,5) P- 4, suggests a mechanism by which Fc gamma RIIB can inhibit calcium inf lux and downstream responses triggered by immune receptors.