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.
Hirano
Masayuki
M
Division of Immunology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Kikuchi
Yuji
Y
Nisitani
Sazuku
S
Yamaguchi
Akiko
A
Satoh
Atsushi
A
Ito
Taiji
T
Iba
Hideo
H
Takatsu
Kiyoshi
K
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology*; D019556:COS Cells; D002467:Cell Nucleus / Q000648:ultrastructure; D002522:Chlorocebus aethiops; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D047468:Immunoprecipitation; D008156:Luciferases / Q000032:analysis / Q000235:genetics; D051379:Mice; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D000071796:SMARCB1 Protein; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D019473:Transcription Factors, TFII / Q000378:metabolism; D015854:Up-Regulation
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C104259:GTF2I protein, human; C493508:Mllt1 protein, mouse; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; C513265:Smarcb1 protein, mouse; D014157:Transcription Factors; D019473:Transcription Factors, TFII; D008156:Luciferases; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; C000625951:Btk protein, mouse