Bruton's tyrosine kinase regulates immunoglobulin promoter activation in association with the transcription factor Bright.
Bright (B-cell regulator of immunoglobulin heavy chain transcription) binding to immunoglobulin heavy chain loci after B-cell activation is associated with increased heavy chain transcription. Our earlier reports demonstrated that Bright coimmunoprecipitates with Bruton's tyrosine kinase (Btk) and that these proteins associate in a DNA-binding complex in primary B cells. B cells from immunodeficient mice with a mutation in Btk failed to produce stable Bright DNA-binding complexes. In order to determine if Btk is important for Bright function, a transcription activation assay was established and analyzed using real-time PCR technology. Cells lacking both Bright and Btk were transfected with Bright and/or Btk along with an immunoglobulin heavy chain reporter construct. Immunoglobulin gene transcription was enhanced when Bright and Btk were coexpressed. In contrast, neither Bright nor Btk alone led to activation of heavy chain transcription. Furthermore, Bright function required both Btk kinase activity and sequences within the pleckstrin homology domain of Btk. Bright was not appreciably phosphorylated by Btk; however, a third tyrosine-phosphorylated protein coprecipitated with Bright. Thus, the ability of Bright to enhance immunoglobulin transcription critically requires functional Btk.
Rajaiya
Jaya
J
Oklahoma Medical Research Foundation, Immunobiology and Cancer Research Program, 825 N.E. 13th St., Oklahoma City, OK 73104, USA.
Hatfield
Melissa
M
Nixon
Jamee C
JC
Rawlings
David J
DJ
Webb
Carol F
CF
D000077329:Agammaglobulinaemia Tyrosine Kinase; D020816:Amino Acid Motifs / Q000235:genetics; D000818:Animals; D001798:Blood Proteins / Q000235:genetics; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017930:Genes, Reporter / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D047468:Immunoprecipitation; D008214:Lymphocytes / Q000378:metabolism; D051379:Mice; D009857:Oncogenes / Q000235:genetics / Q000502:physiology*; D010750:Phosphoproteins / Q000235:genetics; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D017384:Sequence Deletion / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000235:genetics; D015533:Transcriptional Activation / Q000235:genetics / Q000502:physiology*; D014162:Transfection
C097532:Arid3a protein, mouse; D001798:Blood Proteins; D004268:DNA-Binding Proteins; D007143:Immunoglobulin Heavy Chains; D010750:Phosphoproteins; D015534:Trans-Activators; D014157:Transcription Factors; C039077:platelet protein P47; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625951:Btk protein, mouse
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