Abstract
Tec is the prototype of an emerging family of protein-tyrosine kinases. Tec and Btk, another member of this family, together participate in the development of B-cell immune system. We previously identified one of the downstream messengers for human Tec kinase, BRDG1. BRDG1 is associated with Tec and becomes tyrosine-phosphorylated in B-cells by the engagement of B-cell antigen receptor (BCR). Here we show that overexpression of BRDG1 strongly augments BCR-mediated activation of cAMP-response element binding protein (CREB) but not that of c-Jun and the promoters of c-MYC and BCL-xL genes. Furthermore, we isolated the murine orthologue of BRDG1. Three isoforms of BRDG1 are generated by alternative splicing of the message. Two of them have a deletion of 33 amino acids in a Pleckstrin homology (PH) domain of BRDG1. Both the tyrosine-phosphorylation and CREB-activating ability of BRDG1 were isoform-dependent, suggesting a role of the PH domain of BRDG1. These data have identified a novel regulatory mechanism of CREB family of transcriptional factors.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Alternative Splicing
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Amino Acid Sequence
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Animals
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Blotting, Northern
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Carrier Proteins / chemistry*
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Carrier Proteins / metabolism*
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Cell Line
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Cyclic AMP / metabolism
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Cyclic AMP Response Element-Binding Protein / metabolism
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DNA, Complementary / metabolism
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Gene Deletion
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Genes, myc / genetics
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Humans
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Immunoglobulin M / immunology
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Mice
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Mice, Inbred C57BL
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Models, Biological
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Molecular Sequence Data
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Phosphorylation
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Plasmids / metabolism
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Promoter Regions, Genetic
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Protein Binding
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Protein Isoforms
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Protein Structure, Tertiary
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Protein-Tyrosine Kinases / chemistry*
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Protein-Tyrosine Kinases / metabolism*
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-jun / genetics
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Receptors, Antigen, B-Cell / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction
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Tissue Distribution
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Transcription, Genetic
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Transfection
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Tyrosine / metabolism
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bcl-X Protein
Substances
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Adaptor Proteins, Signal Transducing
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BCL2L1 protein, human
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Bcl2l1 protein, mouse
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Carrier Proteins
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Cyclic AMP Response Element-Binding Protein
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DNA, Complementary
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Immunoglobulin M
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Protein Isoforms
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Proto-Oncogene Proteins c-bcl-2
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Proto-Oncogene Proteins c-jun
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Receptors, Antigen, B-Cell
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STAP1 protein, human
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bcl-X Protein
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Tyrosine
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Cyclic AMP
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Tec protein-tyrosine kinase
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Protein-Tyrosine Kinases