title: Role of the inositol phosphatase SHIP in negative regulation of the immune system by the receptor Fc(gamma)RIIB.
abstract: Immune complexes are potent activators of inflammatory cells, triggering effector responses through the crosslinking of Fc receptors (FcRs) such as Fc(epsilon)RI or Fc(gamma)RIII. 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 Fc(epsilon)RI, respectively, and the inhibitory receptor Fc(gamma)RIIB. Here we show that inhibitory signalling by Fc(gamma)RIIB 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 Fc(gamma)RIIB 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 Fc(gamma)RIIB can inhibit calcium influx and downstream responses triggered by immune receptors.
authors.affiliation: Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York 10021, USA.
authors.forename: M
authors.initials: M
authors.lastname: Ono
authors.forename: S
authors.initials: S
authors.lastname: Bolland
authors.forename: P
authors.initials: P
authors.lastname: Tempst
authors.forename: J V
authors.initials: JV
authors.lastname: Ravetch
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002118:Calcium / Q000378:metabolism; D015550:Cell Degranulation; D002460:Cell Line; D047908:Intracellular Signaling Peptides and Proteins; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000502:physiology*; D010766:Phosphorylation; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000502:physiology; D017452:Receptors, IgG / Q000502:physiology*; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D015398:Signal Transduction; D018909:src Homology Domains / Q000502:physiology
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D010455:Peptides; D017452:Receptors, IgG; D010744:Phosphoric Monoester Hydrolases; C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C516725:Ptpn11 protein, mouse; C509248:Ptpn6 protein, mouse; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; C098706:INPPL1 protein, human; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D002118:Calcium