title: CD45 regulates tyrosine phosphorylation of CD22 and its association with the protein tyrosine phosphatase SHP-1.
abstract: 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.
authors.affiliation: Department of Microbiology, Division of Developmental and Clinical Immunology, University of Alabama, Birminghamp55294, USA.
authors.forename: S F
authors.initials: SF
authors.lastname: Greer
authors.forename: L B
authors.initials: LB
authors.lastname: Justement
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism*; D020013:Calcium Signaling / Q000276:immunology; D002384:Catalysis; D015815:Cell Adhesion Molecules; D007424:Intracellular Fluid / Q000201:enzymology / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D037102:Lectins; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000276:immunology; D051379:Mice; D010766:Phosphorylation; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D051918:Sialic Acid Binding Ig-like Lectin 2; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism*; D018909:src Homology Domains / Q000235:genetics / Q000276:immunology; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C497868:Cd22 protein, mouse; D015815:Cell Adhesion Molecules; D047908:Intracellular Signaling Peptides and Proteins; D037102:Lectins; D011947:Receptors, Antigen, B-Cell; D051918:Sialic Acid Binding Ig-like Lectin 2; D014443:Tyrosine; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D017493:Leukocyte Common Antigens; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C516725:Ptpn11 protein, mouse; C509248:Ptpn6 protein, mouse; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases