RRC ID |
67976
|
Author |
Yokohari K, Yamashita Y, Okada S, Ohya K, Oda S, Hatano M, Mano H, Hirasawa H, Tokuhisa T.
|
Title |
Isoform-dependent interaction of BRDG1 with Tec kinase.
|
Journal |
Biochem Biophys Res Commun
|
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.
|
Volume |
289(2)
|
Pages |
414-20
|
Published |
2001-11-30
|
DOI |
10.1006/bbrc.2001.6008
|
PII |
S0006291X01960085
|
PMID |
11716489
|
MeSH |
Adaptor Proteins, Signal Transducing*
Alternative Splicing
Amino Acid Sequence
Animals
Blotting, Northern
Carrier Proteins / chemistry*
Carrier Proteins / metabolism*
Cell Line
Cyclic AMP / metabolism
Cyclic AMP Response Element-Binding Protein / metabolism
DNA, Complementary / metabolism
Gene Deletion
Genes, myc / genetics
Humans
Immunoglobulin M / immunology
Mice
Mice, Inbred C57BL
Models, Biological
Molecular Sequence Data
Phosphorylation
Plasmids / metabolism
Promoter Regions, Genetic
Protein Binding
Protein Isoforms
Protein Structure, Tertiary
Protein-Tyrosine Kinases / chemistry*
Protein-Tyrosine Kinases / metabolism*
Proto-Oncogene Proteins c-bcl-2 / genetics
Proto-Oncogene Proteins c-jun / genetics
Receptors, Antigen, B-Cell / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
Tissue Distribution
Transcription, Genetic
Transfection
Tyrosine / metabolism
bcl-X Protein
|
IF |
2.985
|
Resource |
Human and Animal Cells |
RAW 264(RCB0535) |