PMID- 10327049 OWN - NLM STAT- MEDLINE DCOM- 19990603 LR - 20181201 IS - 0950-9232 (Print) IS - 0950-9232 (Linking) VI - 18 IP - 14 DP - 1999 Apr 8 TI - Paired immunoglobulin-like receptor B (PIR-B) inhibits BCR-induced activation of Syk and Btk by SHP-1. PG - 2291-7 AB - 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. FAU - Maeda, A AU - Maeda A AD - Department of Molecular Genetics, Institute for Liver Research, Kansai Medical University, Moriguchi, Japan. FAU - Scharenberg, A M AU - Scharenberg AM FAU - Tsukada, S AU - Tsukada S FAU - Bolen, J B AU - Bolen JB FAU - Kinet, J P AU - Kinet JP FAU - Kurosaki, T AU - Kurosaki T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Oncogene JT - Oncogene JID - 8711562 RN - 0 (Enzyme Precursors) RN - 0 (Inositol Phosphates) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Isoenzymes) RN - 0 (Pirb protein, mouse) RN - 0 (Receptors, Antigen, B-Cell) RN - 0 (Receptors, IgG) RN - 0 (Receptors, Immunologic) RN - 0 (Recombinant Fusion Proteins) RN - 0 (inositol 3,4,5-trisphosphate) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 2.7.10.2 (Agammaglobulinaemia Tyrosine Kinase) RN - EC 2.7.10.2 (Syk Kinase) RN - EC 2.7.10.2 (Syk protein, mouse) RN - EC 2.7.10.2 (src-Family Kinases) RN - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 11) RN - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 6) RN - EC 3.1.3.48 (Protein Tyrosine Phosphatases) RN - EC 3.1.3.48 (Ptpn11 protein, mouse) RN - EC 3.1.3.48 (Ptpn6 protein, mouse) RN - EC 3.1.4.- (Type C Phospholipases) RN - EC 3.1.4.3 (Phospholipase C gamma) SB - IM MH - Agammaglobulinaemia Tyrosine Kinase MH - Animals MH - Calcium Signaling/physiology MH - Cell Line MH - Enzyme Activation MH - Enzyme Precursors/*metabolism MH - Inositol Phosphates/metabolism MH - Intracellular Signaling Peptides and Proteins MH - Isoenzymes/antagonists & inhibitors MH - Mice MH - Models, Biological MH - Phospholipase C gamma MH - Phosphorylation MH - Protein Processing, Post-Translational/*physiology MH - Protein Tyrosine Phosphatase, Non-Receptor Type 11 MH - Protein Tyrosine Phosphatase, Non-Receptor Type 6 MH - Protein Tyrosine Phosphatases/*physiology MH - Protein-Tyrosine Kinases/*metabolism MH - Receptors, Antigen, B-Cell/*immunology MH - Receptors, IgG/genetics MH - Receptors, Immunologic/genetics/*physiology MH - Recombinant Fusion Proteins/physiology MH - Syk Kinase MH - Transfection MH - Type C Phospholipases/antagonists & inhibitors MH - src-Family Kinases/metabolism EDAT- 1999/05/18 00:00 MHDA- 1999/05/18 00:01 CRDT- 1999/05/18 00:00 PHST- 1999/05/18 00:00 [pubmed] PHST- 1999/05/18 00:01 [medline] PHST- 1999/05/18 00:00 [entrez] AID - 10.1038/sj.onc.1202552 [doi] PST - ppublish SO - Oncogene. 1999 Apr 8;18(14):2291-7. doi: 10.1038/sj.onc.1202552.