Isoform-dependent interaction of BRDG1 with Tec kinase.
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.
Yokohari
K
K
Department of Developmental Genetics, Chiba University Graduate School of Medicine, Inohana 1-8-1, Chuo-ku, Chiba 260-8670, Japan.
Yamashita
Y
Y
Okada
S
S
Ohya
K
K
Oda
S
S
Hatano
M
M
Mano
H
H
Hirasawa
H
H
Tokuhisa
T
T
D048868:Adaptor Proteins, Signal Transducing; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D017353:Gene Deletion; D016259:Genes, myc / Q000235:genetics; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D008969:Molecular Sequence Data; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000737:chemistry* / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014018:Tissue Distribution; D014158:Transcription, Genetic; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism; D051020:bcl-X Protein
D048868:Adaptor Proteins, Signal Transducing; C494811:BCL2L1 protein, human; C494812:Bcl2l1 protein, mouse; D002352:Carrier Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D018076:DNA, Complementary; D007075:Immunoglobulin M; D020033:Protein Isoforms; D019253:Proto-Oncogene Proteins c-bcl-2; D016755:Proto-Oncogene Proteins c-jun; D011947:Receptors, Antigen, B-Cell; C400186:STAP1 protein, human; D051020:bcl-X Protein; D014443:Tyrosine; D000242:Cyclic AMP; C089848:Tec protein-tyrosine kinase; D011505:Protein-Tyrosine Kinases