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
Human and Animal Cells RAW 264(RCB0535)