Role of the Inositol Phosphatase SHIP in Negative Regulation of the Immune System by the Receptor Fc(gamma)RIIB

Nature. 1996 Sep 19;383(6597):263-6. doi: 10.1038/383263a0.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • B-Lymphocytes / immunology*
  • Calcium / metabolism
  • Cell Degranulation
  • Cell Line
  • Intracellular Signaling Peptides and Proteins
  • Mast Cells / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Peptides / immunology
  • Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
  • Phosphoric Monoester Hydrolases / physiology*
  • Phosphorylation
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases / physiology
  • Receptors, IgG / physiology*
  • SH2 Domain-Containing Protein Tyrosine Phosphatases
  • Signal Transduction
  • src Homology Domains / physiology

Substances

  • Intracellular Signaling Peptides and Proteins
  • Peptides
  • Receptors, IgG
  • Phosphoric Monoester Hydrolases
  • PTPN11 protein, human
  • PTPN6 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases
  • Ptpn11 protein, mouse
  • Ptpn6 protein, mouse
  • SH2 Domain-Containing Protein Tyrosine Phosphatases
  • INPPL1 protein, human
  • Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
  • Calcium