Abstract
The function and regulation of the receptorlike transmembrane protein tyrosine phosphatases (RPTPs) are not well understood. Ligand-induced dimerization inhibited the function of the epidermal growth factor receptor (EGFR)-RPTP CD45 chimera (EGFR-CD45) in T cell signal transduction. Properties of mutated EGFR-CD45 chimeras supported a general model for the regulation of RPTPs, derived from the crystal structure of the RPTPalpha membrane-proximal phosphatase domain. The phosphatase domain apparently forms a symmetrical dimer in which the catalytic site of one molecule is blocked by specific contacts with a wedge from the other.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Binding Sites
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Calcium / metabolism
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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Dimerization
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Epidermal Growth Factor / metabolism
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Epidermal Growth Factor / pharmacology
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ErbB Receptors / chemistry
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ErbB Receptors / metabolism
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Humans
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Leukocyte Common Antigens / chemistry
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Leukocyte Common Antigens / metabolism*
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Ligands
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Lymphocyte Activation
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Mutation
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Phosphorylation
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Protein Tyrosine Phosphatases / antagonists & inhibitors*
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Protein Tyrosine Phosphatases / chemistry
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Protein Tyrosine Phosphatases / metabolism
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Protein-Tyrosine Kinases / metabolism
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Receptors, Antigen, T-Cell / metabolism
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Recombinant Fusion Proteins / antagonists & inhibitors
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / metabolism
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Signal Transduction
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism*
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Tumor Cells, Cultured
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ZAP-70 Protein-Tyrosine Kinase
Substances
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Ligands
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Receptors, Antigen, T-Cell
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Recombinant Fusion Proteins
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Epidermal Growth Factor
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ErbB Receptors
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Protein-Tyrosine Kinases
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ZAP-70 Protein-Tyrosine Kinase
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ZAP70 protein, human
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Calcium-Calmodulin-Dependent Protein Kinases
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Leukocyte Common Antigens
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Protein Tyrosine Phosphatases
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Calcium