The transcription factor Bright associates with Bruton's tyrosine kinase, the defective protein in immunodeficiency disease

J Immunol. 2000 Dec 15;165(12):6956-65. doi: 10.4049/jimmunol.165.12.6956.

Abstract

Binding of the transcription factor Bright to Ig heavy chain loci after B cell activation is associated with increased heavy chain transcription. We now report that Bright coprecipitates with Bruton's tyrosine kinase (Btk), the defective enzyme in X-linked immunodeficiency disease (xid). Furthermore, we observed Btk in the nucleus of activated murine B cells, and mobility shift assays suggest that it is a component of the Bright DNA-binding complex. While BRIGHT protein was synthesized in activated spleen cells from xid mice, it did not bind DNA or associate stably with Btk. These data suggest that deficiencies in BRIGHT DNA-binding activity may contribute to the defects in Ig production seen in xid mice.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Active Transport, Cell Nucleus / immunology
  • Agammaglobulinaemia Tyrosine Kinase
  • Animals
  • B-Lymphocytes / enzymology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • CD40 Ligand / pharmacology
  • Cell Nucleus / enzymology
  • Cell Nucleus / immunology
  • Cells, Cultured
  • DNA / metabolism
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism*
  • Female
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulin Heavy Chains / metabolism
  • Immunologic Deficiency Syndromes / enzymology*
  • Immunologic Deficiency Syndromes / genetics
  • Immunologic Deficiency Syndromes / metabolism
  • Lipopolysaccharides / pharmacology
  • Lymphocyte Activation
  • Macromolecular Substances
  • Male
  • Mice
  • Mice, Inbred CBA
  • Mice, Mutant Strains
  • Oncogenes*
  • Protein Binding
  • Protein-Tyrosine Kinases / chemistry
  • Protein-Tyrosine Kinases / metabolism*
  • Spleen / enzymology
  • Spleen / immunology
  • Spleen / pathology
  • Trans-Activators / biosynthesis
  • Trans-Activators / chemistry
  • Trans-Activators / metabolism*
  • Transcription Factors

Substances

  • Arid3a protein, mouse
  • DNA-Binding Proteins
  • Immunoglobulin Heavy Chains
  • Lipopolysaccharides
  • Macromolecular Substances
  • Trans-Activators
  • Transcription Factors
  • CD40 Ligand
  • DNA
  • Protein-Tyrosine Kinases
  • Agammaglobulinaemia Tyrosine Kinase
  • Btk protein, mouse