The human high-affinity immunoglobulin G receptor activates SH2-containing inositol phosphatase (SHIP).
On cytokine-primed U937 cells, aggregation of the human high-affinity immunoglobulin receptor, FcgammaRI, initiates signal transduction cascades which lead to the release of calcium from intracellular stores and no significant calcium influx. In these cells, aggregation of FcgammaRI results in no significant increase in inositol trisphosphate production, but rather phospholipase D is activated. Here we show that, in interferon-gamma (IFN-gamma)-primed cells, the SH2 containing inositol 5' phosphatase, SHIP, is constitutively associated with the membrane fraction. Following aggregation of FcgammaRI, SHIP is rapidly and transiently tyrosine phosphorylated and becomes associated with the adapter molecule Shc. Shc also becomes tyrosine phosphorylated and translocates from the cytoplasm to the membrane fraction concomitant with the association between Shc and SHIP. Further, SHIP and Shc appear to be recruited to membrane-associated immune complexes following FcgammaRI aggregation. As no immunoreceptor inhibitory motif has been demonstrated to associate with FcgammaRI, these data suggest that SHIP may be recruited to the receptor through an SH2 domain interaction with Shc.
Cameron
A J
AJ
Department of Medicine and Therapeutics and Division of Biochemistry and Molecular Biology, University of Glasgow, Glasgow G12 8QQ, UK.
Allen
J M
JM
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism; D015153:Blotting, Western; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D051379:Mice; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism; D017452:Receptors, IgG / Q000276:immunology*; D055765:Shc Signaling Adaptor Proteins; D015398:Signal Transduction / Q000276:immunology; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism; D020298:U937 Cells; D018909:src Homology Domains
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000936:Antigen-Antibody Complex; D011506:Proteins; D017452:Receptors, IgG; C528024:SHC1 protein, human; D055765:Shc Signaling Adaptor Proteins; C528034:Shc1 protein, mouse; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D014443:Tyrosine; D007371:Interferon-gamma; D010744:Phosphoric Monoester Hydrolases; C098706:INPPL1 protein, human; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases