Bruton's tyrosine kinase (Btk) enhances transcriptional co-activation activity of BAM11, a Btk-associated molecule of a subunit of SWI/SNF complexes.
Bruton's tyrosine kinase (Btk) is required for B cell development and signal transduction through cell-surface molecules such as BCR and IL-5 receptor. We have identified a Btk-associated molecule, BAM11 (hereafter referred to as BAM) that binds to the pleckstrin homology (PH) domain of Btk, and inhibits Btk activity both in ... vivo and in vitro. In this study, we demonstrate BAM's transcriptional co-activation activity and its functional interaction with Btk. By using transient transcription assays, we demonstrate that the enforced expression of BAM enhances transcriptional activity of the synthetic reporter gene. The C-terminus of BAM is essential for the transcriptional co-activation activity. The ectopic expression of Btk together with BAM enhances BAM's transcriptional co-activation activity. BAM's transcriptional co-activation activity is enhanced through interaction with Btk, and requires both its intact PH domain and functional kinase activity. We also show that enforced expression of TFII-I, another Btk-binding protein with transcriptional activity, together with BAM and Btk, further augments BAM- and Btk-dependent transcriptional co-activation. Furthermore, BAM can be co-immunoprecipitated with the INI1/SNF5 protein, a member of the SWI/SNF complex that remodels chromatin and activates transcription. We propose a model in which Btk regulates gene transcription in B cells by activating BAM and the SWI/SNF transcriptional complex via TFII-I activation.
Mesh Terms:
Animals, B-Lymphocytes, COS Cells, Cell Nucleus, Cercopithecus aethiops, Chromosomal Proteins, Non-Histone, DNA-Binding Proteins, Gene Deletion, Genes, Reporter, Humans, Immunoprecipitation, Luciferases, Mice, Protein Binding, Protein Interaction Mapping, Protein Structure, Tertiary, Protein-Tyrosine Kinases, Transcription Factors, Transcription Factors, TFII, Up-Regulation
Animals, B-Lymphocytes, COS Cells, Cell Nucleus, Cercopithecus aethiops, Chromosomal Proteins, Non-Histone, DNA-Binding Proteins, Gene Deletion, Genes, Reporter, Humans, Immunoprecipitation, Luciferases, Mice, Protein Binding, Protein Interaction Mapping, Protein Structure, Tertiary, Protein-Tyrosine Kinases, Transcription Factors, Transcription Factors, TFII, Up-Regulation
Int. Immunol.
Date: May. 01, 2004
PubMed ID: 15096481
View in: Pubmed Google Scholar
Download Curated Data For This Publication
113889
Switch View:
- Interactions 4