Abstract
The signal transduction events supporting B cell antigen receptor (BCR) endocytosis are not well understood. We have identified a pathway supporting BCR internalization that begins with tyrosine phosphorylation of the adapter protein LAB. Phosphorylated LAB recruits a complex of Grb2-dynamin and the guanine nucleotide exchange factor Vav. Vav is required for activation of the small GTPases Rac1 and Rac2. All these proteins contribute to (and dynamin, Vav, and Rac1/2 are required for) BCR endocytosis and presentation of antigen to T cells. This is the first description of a sequential signal transduction pathway from BCR to internalization and antigen presentation.
MeSH terms
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Adaptor Proteins, Vesicular Transport / genetics
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Adaptor Proteins, Vesicular Transport / immunology
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Adaptor Proteins, Vesicular Transport / metabolism*
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Animals
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Antigen Presentation / physiology
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B-Lymphocytes / immunology
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B-Lymphocytes / metabolism*
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Cell Line, Tumor
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Dynamins / genetics
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Dynamins / immunology
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Dynamins / metabolism
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Endocytosis / physiology*
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GRB2 Adaptor Protein / genetics
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GRB2 Adaptor Protein / immunology
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GRB2 Adaptor Protein / metabolism
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Mice
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Mice, Inbred BALB C
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Mice, Knockout
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Neuropeptides / genetics
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Neuropeptides / immunology
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Neuropeptides / metabolism*
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Phosphorylation / physiology
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Proto-Oncogene Proteins c-vav / genetics
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Proto-Oncogene Proteins c-vav / immunology
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Proto-Oncogene Proteins c-vav / metabolism*
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RAC2 GTP-Binding Protein
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Receptors, Antigen, B-Cell / genetics
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Receptors, Antigen, B-Cell / immunology
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Receptors, Antigen, B-Cell / metabolism*
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Signal Transduction / physiology
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism
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rac GTP-Binding Proteins / genetics
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rac GTP-Binding Proteins / immunology
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rac GTP-Binding Proteins / metabolism*
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rac1 GTP-Binding Protein
Substances
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Adaptor Proteins, Vesicular Transport
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GRB2 Adaptor Protein
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Grb2 protein, mouse
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LAB protein, mouse
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Neuropeptides
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Proto-Oncogene Proteins c-vav
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Rac1 protein, mouse
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Receptors, Antigen, B-Cell
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rac GTP-Binding Proteins
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rac1 GTP-Binding Protein
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Dynamins