Selective in vivo recruitment of the phosphatidylinositol phosphatase SHIP by phosphorylated Fc gammaRIIB during negative regulation of IgE-dependent mouse mast cell activation.
We demonstrated previously that the low-affinity IgG receptors Fc gammaRIIB, which are coexpressed with the high-affinity IgE receptors Fc epsilonRI in mouse mast cells, can inhibit IgE-induced release of inflammatory mediators and cytokines by these cells. Inhibition was found to require the coaggregation of the two receptors and to depend on the presence of a tyrosine-based inhibition motif (ITIM) in the intracytoplasmic domain of Fc gammaRIIB. We report here that the coaggregation with Fc gammaRIIB does not prevent Fc epsilonRI from triggering activation signals in BMMC and induces the tyrosine phosphorylation of Fc gammaRIIB. Phosphorylated ITIM peptides bound in vitro to three SH2 domain-containing phosphatases present in BMMC lysates: the phosphotyrosine phosphatases SHP-1 and SHP-2. and the inositolphosphate phosphatase SHIP. Using BMMC generated from the SHP-1-deficient motheaten mice, SHP-1 was found to be dispensable for inhibition of mast cell activation. When analyzed for in vivo association, SHIP coprecipitated with phosphorylated Fc gammaRIIB, whereas SHP-1 or SHP-2 did not. These observations altogether indicate that Fc epsilonRI actively participates in its own regulation and that the mechanisms by which Fc gammaRIIB inhibit cell activation might be different in mast cells and in B-cells.
Fong
D C
DC
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO, USA.
Malbec
O
O
Arock
M
M
Cambier
J C
JC
Fridman
W H
WH
Daëron
M
M
D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D007073:Immunoglobulin E / Q000276:immunology*; D008407:Mast Cells / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008934:Mitogens / Q000494:pharmacology; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000276:immunology*; D010766:Phosphorylation; D011817:Rabbits; D017455:Receptors, IgE / Q000276:immunology; D017452:Receptors, IgG / Q000276:immunology*; D012701:Serotonin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D018909:src Homology Domains / Q000276:immunology*
D015703:Antigens, CD; C080571:Fc gamma receptor IIB; D008934:Mitogens; D017455:Receptors, IgE; D017452:Receptors, IgG; D012701:Serotonin; D007073:Immunoglobulin E; D010744:Phosphoric Monoester Hydrolases; C098706:INPPL1 protein, human; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases