The human high-affinity immunoglobulin G receptor activates SH2-containinginositol phosphatase (SHIP)

On cytokine-primed U937 cells, aggregation of the human high-affinity immun oglobulin receptor, Fc gamma RI, initiates signal transduction cascades whi ch lead to the release of calcium from intracellular stores and no signific ant calcium influx. In these cells, aggregation of Fc gamma RI results in n o significant increase in inositol trisphosphate production, but rather pho spholipase D is activated. Here we show that, in interferon-gamma (IFN-gamm a)-primed cells, the SH2 containing inositol 5' phosphatase, SHIP, is const itutively associated with the membrane fraction. Following aggregation of F c gamma RI, SHIP is rapidly and transiently tyrosine phosphorylated and bec omes associated with the adapter molecule Shc. Shc also becomes tyrosine ph osphorylated and translocates from the cytoplasm to the membrane fraction c oncomitant with the association between Shc and SHIP. Further, SHIP and Shc appear to be recruited to membrane-associated immune complexes following F c gamma RI aggregation. As no immunoreceptor inhibitory motif has been demo nstrated to associate with Fc gamma RI, these data suggest that SHIP may be recruited to the receptor through an SH2 domain interaction with Shc.