We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Signalling of the BCR is regulated by a lipid rafts-localised transcription factor, Bright.
- Authors
Schmidt, Christian; Kim, Dongkyoon; Ippolito, Gregory C.; Naqvi, Hassan R.; Probst, Loren; Mathur, Shawn; Rosas-Acosta, German; Wilson, Van G.; Oldham, Athenia L.; Poenie, Martin; Webb, Carol F.; Tucker, Philip W.
- Abstract
Regulation of BCR signalling strength is crucial for B-cell development and function. Bright is a B-cell-restricted factor that complexes with Bruton's tyrosine kinase (Btk) and its substrate, transcription initiation factor-I (TFII-I), to activate immunoglobulin heavy chain gene transcription in the nucleus. Here we show that a palmitoylated pool of Bright is diverted to lipid rafts of resting B cells where it associates with signalosome components. After BCR ligation, Bright transiently interacts with sumoylation enzymes, blocks calcium flux and phosphorylation of Btk and TFII-I and is then discharged from lipid rafts as a Sumo-I-modified form. The resulting lipid raft concentration of Bright contributes to the signalling threshold of B cells, as their sensitivity to BCR stimulation decreases as the levels of Bright increase. Bright regulates signalling independent of its role in IgH transcription, as shown by specific dominant-negative titration of rafts-specific forms. This study identifies a BCR tuning mechanism in lipid rafts that is regulated by differential post-translational modification of a transcription factor with implications for B-cell tolerance and autoimmunity.
- Subjects
B cell lymphoma; LYMPHOMAS; LYMPHOCYTES; PROTEIN-tyrosine kinases; PROTEIN kinases; CHEMICAL reactions
- Publication
EMBO Journal, 2009, Vol 28, Issue 6, p711
- ISSN
0261-4189
- Publication type
Article
- DOI
10.1038/emboj.2009.20