| First Author | Schmidt C | Year | 2009 |
| Journal | EMBO J | Volume | 28 |
| Issue | 6 | Pages | 711-24 |
| PubMed ID | 19214191 | Mgi Jnum | J:146814 |
| Mgi Id | MGI:3838472 | Doi | 10.1038/emboj.2009.20 |
| Citation | Schmidt C, et al. (2009) Signalling of the BCR is regulated by a lipid rafts-localised transcription factor, Bright. EMBO J 28(6):711-24 |
| abstractText | 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. |
