Abstract
The adaptor Nck links receptor signaling to cytoskeleton regulation. Here we found that Nck also controlled the phosphatidylinositol-3-OH kinase (PI(3)K)-kinase Akt pathway by recruiting the adaptor BCAP after activation of B cells. Nck bound directly to the B cell antigen receptor (BCR) via the non-immunoreceptor tyrosine-based activation motif (ITAM) phosphorylated tyrosine residue at position 204 in the tail of the immunoglobulin-α component. Genetic ablation of Nck resulted in defective BCR signaling, which led to hampered survival and proliferation of B cells in vivo. Indeed, antibody responses in Nck-deficient mice were also considerably impaired. Thus, we demonstrate a previously unknown adaptor function for Nck in recruiting BCAP to sites of BCR signaling and thereby modulating the PI(3)K-Akt pathway in B cells.
MeSH terms
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Adaptor Proteins, Signal Transducing / deficiency
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / metabolism*
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Animals
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B-Lymphocytes / immunology
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B-Lymphocytes / metabolism*
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Female
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Immunoglobulin alpha-Chains / chemistry
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Immunoglobulin alpha-Chains / metabolism
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Male
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Mice
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Mice, Knockout
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Oncogene Proteins / deficiency
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Oncogene Proteins / genetics
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Oncogene Proteins / metabolism*
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Phosphatidylinositol 3-Kinases / metabolism*
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Phosphorylation
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Protein Binding
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Proto-Oncogene Proteins c-akt / metabolism*
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Receptors, Antigen, B-Cell / 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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Tyrosine / metabolism
Substances
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Adaptor Proteins, Signal Transducing
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Immunoglobulin alpha-Chains
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Nck protein
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Oncogene Proteins
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Pik3ap1 protein, mouse
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Receptors, Antigen, B-Cell
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Tyrosine
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Phosphatidylinositol 3-Kinases
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Proto-Oncogene Proteins c-akt