Requirement of SH2-containing protein tyrosine phosphatases SHP-1 and SHP-2 for paired immunoglobulin-like receptor B (PIR-B)-mediated inhibitory signal

A Maeda; M Kurosaki; M Ono; T Takai; T Kurosaki

doi:10.1084/jem.187.8.1355

Requirement of SH2-containing protein tyrosine phosphatases SHP-1 and SHP-2 for paired immunoglobulin-like receptor B (PIR-B)-mediated inhibitory signal

J Exp Med. 1998 Apr 20;187(8):1355-60. doi: 10.1084/jem.187.8.1355.

Authors

A Maeda¹, M Kurosaki, M Ono, T Takai, T Kurosaki

Affiliation

¹ Department of Molecular Genetics, Institute for Liver Research, Kansai Medical University, Moriguchi 570, Japan.

Abstract

Paired immunoglobulin-like receptor B (PIR-B) (p91) molecule has been proposed to function as an inhibitory receptor in B cells and myeloid lineage cells. We demonstrate here that the cytoplasmic region of PIR-B is capable of inhibiting B cell activation. Mutational analysis of five cytoplasmic tyrosines indicate that tyrosine 771 in the motif VxYxxL plays the most crucial role in mediating the inhibitory signal. PIR-B-mediated inhibition was markedly reduced in the SH2-containing protein tyrosine phosphatases SHP-1 and SHP-2 double-deficient DT40 B cells, whereas this inhibition was unaffected in the inositol polyphosphate 5'-phosphatase SHIP-deficient cells. These data demonstrate that PIR-B can negatively regulate B cell receptor activation and that this PIR-B-mediated inhibition requires redundant functions of SHP-1 and SHP-2.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antigens, CD / metabolism
B-Lymphocytes / immunology*
Bone Marrow Cells / immunology
Calcium / metabolism
DNA Mutational Analysis
Intracellular Signaling Peptides and Proteins
Lymphocyte Activation*
Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
Phosphoric Monoester Hydrolases / metabolism
Protein Tyrosine Phosphatase, Non-Receptor Type 11
Protein Tyrosine Phosphatase, Non-Receptor Type 6
Protein Tyrosine Phosphatases / metabolism*
Receptors, Antigen, B-Cell / antagonists & inhibitors*
Receptors, IgG / metabolism
Receptors, Immunologic / metabolism*
Signal Transduction

Substances

Antigens, CD
Fc gamma receptor IIB
Intracellular Signaling Peptides and Proteins
Pirb protein, mouse
Receptors, Antigen, B-Cell
Receptors, IgG
Receptors, Immunologic
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
INPPL1 protein, human
Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
Calcium