CD45 regulates tyrosine phosphorylation of CD22 and its association with the protein tyrosine phosphatase SHP-1.
Cross-linking of CD45 induced capping and physical sequestration from CD22 leading to an increase in tyrosine phosphorylation of CD22 and SHP-1 recruitment. Additionally, CD22 isolated from a CD45-deficient B cell line exhibited increased basal/inducible tyrosine phosphorylation and enhanced recruitment of SHP-1 compared with CD22 isolated from CD45-positive parental cells. Subsequent ... experiments were performed to determine whether enhanced SHP-1 recruitment to CD22 is responsible for attenuation of receptor-mediated Ca2+ responses in CD45-deficient cells. Catalytically inactive SHP-1 expressed in CD45-deficient cells interacted with CD22 and decreased phosphatase activity in CD22 immunoprecipitates to levels that were comparable to those in CD45-positive cells. Expression of catalytically inactive SHP-1 restored intracellular mobilization of Ca2+ in response to MHC class II cross-linking, but did not affect B cell Ag receptor- or class II-mediated Ca2+ influx from the extracellular space. These results indicate that CD45 regulates tyrosine phosphorylation of CD22 and binding of SHP-1. The data further indicate that enhanced recruitment and activation of SHP-1 in CD45-deficient cells affect intracellular mobilization of Ca2+, but are not responsible for abrogation of receptor-mediated Ca2+ influx from the extracellular space.
Mesh Terms:
Animals, Antigens, CD, Antigens, CD22, Antigens, CD45, Antigens, Differentiation, B-Lymphocyte, Calcium Signaling, Catalysis, Cell Adhesion Molecules, Intracellular Fluid, Intracellular Signaling Peptides and Proteins, Lectins, Lymphoma, B-Cell, Mice, Phosphorylation, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Protein Tyrosine Phosphatases, Receptors, Antigen, B-Cell, SH2 Domain-Containing Protein Tyrosine Phosphatases, Tumor Cells, Cultured, Tyrosine, src Homology Domains, src-Family Kinases
Animals, Antigens, CD, Antigens, CD22, Antigens, CD45, Antigens, Differentiation, B-Lymphocyte, Calcium Signaling, Catalysis, Cell Adhesion Molecules, Intracellular Fluid, Intracellular Signaling Peptides and Proteins, Lectins, Lymphoma, B-Cell, Mice, Phosphorylation, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Protein Tyrosine Phosphatases, Receptors, Antigen, B-Cell, SH2 Domain-Containing Protein Tyrosine Phosphatases, Tumor Cells, Cultured, Tyrosine, src Homology Domains, src-Family Kinases
J. Immunol.
Date: May. 01, 1999
PubMed ID: 10228003
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