Hematopoietic cell phosphatase is recruited to CD22 following B cell antigen receptor ligation.
Hematopoietic cell phosphatase is a nonreceptor protein tyrosine phosphatase that is preferentially expressed in hematopoietic cell lineages. Motheaten mice, which are devoid of (functional) hematopoietic cell phosphatase, have severe disturbances in the regulation of B cell activation and differentiation. Because signals transduced via the B cell antigen receptor are known to guide these processes, we decided to analyze molecular interactions between the hematopoietic cell phosphatase and the B cell antigen receptor. Ligation of the B cell antigen receptor induces moderate tyrosine phosphorylation of hematopoietic cell phosphatase and the formation of a multi-molecular complex containing additional 68-70- and 135-kDa phosphoproteins. In resting B cells most of the hematopoietic cell phosphatase proteins reside in the cytosolic compartment, whereas after B cell antigen receptor cross-linking, a small fraction translocates toward the membrane where it specifically binds to the 135-kDa phosphoprotein. This 135-kDa glycoprotein was identified as CD22, a transmembrane associate of the B cell antigen receptor complex. Together these findings provide the first direct evidence that this cytoplasmic tyrosine phosphatase is involved in antigen receptor-mediated B cell activation, suggesting that in vivo B cell antigen receptor constituents or associated molecules may serve as substrate for its catalytic activity.
Lankester
A C
AC
Central Laboratory of the Blood Transfusion Service, The Netherlands Red Cross, University of Amsterdam.
van Schijndel
G M
GM
van Lier
R A
RA
D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000302:isolation & purification / Q000378:metabolism*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000302:isolation & purification / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology*; D015153:Blotting, Western; D002051:Burkitt Lymphoma; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D003432:Cross-Linking Reagents; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D037102:Lectins; D008213:Lymphocyte Activation; D008970:Molecular Weight; D014066:Palatine Tonsil / Q000276:immunology; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism*; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000302:isolation & purification / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D051918:Sialic Acid Binding Ig-like Lectin 2; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C497867:CD22 protein, human; D015815:Cell Adhesion Molecules; D003432:Cross-Linking Reagents; D047908:Intracellular Signaling Peptides and Proteins; D037102:Lectins; D010750:Phosphoproteins; D011947:Receptors, Antigen, B-Cell; D051918:Sialic Acid Binding Ig-like Lectin 2; C509249:PTPN6 protein, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases