Abstract
Cross-linking B cell antigen receptor (BCR) elicits early signal transduction events, including activation of protein tyrosine kinases, phosphorylation of receptor components, activation of phospholipase C-gamma (PLC-gamma), and increases in intracellular free Ca2+. In this article, we report that cross-linking the BCR led to a rapid translocation of cytosolic protein tyrosine phosphatase (PTP) 1C to the particulate fraction, where it became associated with a 140-150-kD tyrosyl-phosphorylated protein. Western blotting analysis identified this 140-150-kD protein to be CD22. The association of PTP-1C with CD22 was mediated by the NH2-terminal Src homology 2 (SH2) domain of PTP-1C. Complexes of either CD22/PTP-1C/Syk/PLC-gamma(1) could be isolated from B cells stimulated by BCR engagement or a mixture of hydrogen peroxidase and sodium orthovanadate, respectively. The binding of PLC-gamma(1) and Syk to tyrosyl-phosphorylated CD22 was mediated by the NH2-terminal SH2 domain of PLC-gamma(1) and the COOH-terminal SH2 domain of Syk, respectively. These observations suggest that tyrosyl-phosphorylated CD22 may downmodulate the activity of this complex by dephosphorylation of CD22, Syk, and/or PLC-gamma(1). Transient expression of CD22 and a null mutant of PTP-1C (PTP-1CM) in COS cells resulted in an increase in tyrosyl phosphorylation of CD22 and its interaction with PTP-1CM. By contrast, CD22 was not tyrosyl phosphorylated or associated with PTP-1CM in the presence of wild-type PTP-1C. These results suggest that tyrosyl-phosphorylated CD22 may be a substrate for PTP-1C regulates tyrosyl phosphorylation of CD22.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Antigens, CD / genetics
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Antigens, CD / metabolism*
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Antigens, Differentiation, B-Lymphocyte / genetics
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Antigens, Differentiation, B-Lymphocyte / metabolism*
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B-Lymphocytes / immunology*
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Base Sequence
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Calcium / metabolism
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Cell Adhesion Molecules*
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Cross-Linking Reagents
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Enzyme Precursors / metabolism*
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Humans
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Intracellular Signaling Peptides and Proteins
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Isoenzymes / metabolism*
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Lectins*
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Lymphocyte Activation*
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Macromolecular Substances
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Models, Molecular
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Molecular Sequence Data
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Phospholipase C gamma
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Phosphorylation
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Protein Binding
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Protein Tyrosine Phosphatase, Non-Receptor Type 11
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Protein Tyrosine Phosphatase, Non-Receptor Type 6
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Protein Tyrosine Phosphatases / genetics
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Protein Tyrosine Phosphatases / metabolism*
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Protein-Tyrosine Kinases / metabolism*
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Receptors, Antigen, B-Cell / metabolism
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SH2 Domain-Containing Protein Tyrosine Phosphatases
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Sialic Acid Binding Ig-like Lectin 2
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Signal Transduction
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Syk Kinase
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Transfection
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Tumor Cells, Cultured
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Type C Phospholipases / metabolism*
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src Homology Domains
Substances
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Antigens, CD
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Antigens, Differentiation, B-Lymphocyte
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CD22 protein, human
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Cell Adhesion Molecules
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Cross-Linking Reagents
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Enzyme Precursors
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Intracellular Signaling Peptides and Proteins
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Isoenzymes
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Lectins
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Macromolecular Substances
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Receptors, Antigen, B-Cell
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Sialic Acid Binding Ig-like Lectin 2
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Protein-Tyrosine Kinases
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SYK protein, human
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Syk Kinase
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PTPN11 protein, human
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PTPN6 protein, human
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Protein Tyrosine Phosphatase, Non-Receptor Type 11
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Protein Tyrosine Phosphatase, Non-Receptor Type 6
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Protein Tyrosine Phosphatases
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SH2 Domain-Containing Protein Tyrosine Phosphatases
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Type C Phospholipases
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Phospholipase C gamma
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Calcium