Paired immunoglobulin-like receptor B (PIR-B) inhibits BCR-induced activation of Syk and Btk by SHP-1

Oncogene. 1999 Apr 8;18(14):2291-7. doi: 10.1038/sj.onc.1202552.

Abstract

Coligation of paired immunoglobulin-like receptor B (PIR-B) with B cell antigen receptor (BCR) blocks antigen-induced B cell activation. This inhibition is mediated in part by recruitment of SHP-1 and SHP-2 to the phosphorylated ITIMs in the cytoplasmic domain of PIR-B; however the molecular target(s) of these phosphatases remain elusive. Here we show that PIR-B ligation inhibits the BCR-induced tyrosine phosphorylation of Igalpha/Igbeta, Syk, Btk and phospholipase C (PLC)-gamma2. Overexpression of a catalytically inactive form of SHP-1 prevents the PIR-B-mediated inhibition of tyrosine phosphorylation of Syk, Btk, and PLC-gamma2. Dephosphorylation of Syk and Btk mediated by SHP-1 leads to a decrease of their kinase activity, which in turn inhibits tyrosine phosphorylation of PLC-gamma2. Furthermore, we define a requirement for Lyn in mediating tyrosine phosphorylation of PIR-B. Based on these results, we propose a model of PIR-B-mediated inhibitory signaling in which coligation of PIR-B and BCR results in phosphorylation of ITIMs by Lyn, subsequent recruitment of SHP-1, and a resulting inhibition of the BCR-induced inositol 1,4,5-trisphosphate generation by dephosphorylation of Syk and Btk.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agammaglobulinaemia Tyrosine Kinase
  • Animals
  • Calcium Signaling / physiology
  • Cell Line
  • Enzyme Activation
  • Enzyme Precursors / metabolism*
  • Inositol Phosphates / metabolism
  • Intracellular Signaling Peptides and Proteins
  • Isoenzymes / antagonists & inhibitors
  • Mice
  • Models, Biological
  • Phospholipase C gamma
  • Phosphorylation
  • Protein Processing, Post-Translational / physiology*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases / physiology*
  • Protein-Tyrosine Kinases / metabolism*
  • Receptors, Antigen, B-Cell / immunology*
  • Receptors, IgG / genetics
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / physiology*
  • Recombinant Fusion Proteins / physiology
  • Syk Kinase
  • Transfection
  • Type C Phospholipases / antagonists & inhibitors
  • src-Family Kinases / metabolism

Substances

  • Enzyme Precursors
  • Inositol Phosphates
  • Intracellular Signaling Peptides and Proteins
  • Isoenzymes
  • Pirb protein, mouse
  • Receptors, Antigen, B-Cell
  • Receptors, IgG
  • Receptors, Immunologic
  • Recombinant Fusion Proteins
  • inositol 3,4,5-trisphosphate
  • Protein-Tyrosine Kinases
  • Agammaglobulinaemia Tyrosine Kinase
  • Syk Kinase
  • Syk protein, mouse
  • src-Family Kinases
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases
  • Ptpn11 protein, mouse
  • Ptpn6 protein, mouse
  • Type C Phospholipases
  • Phospholipase C gamma