B-cell antigen receptor activates transcription factors NFAT (nuclear factor of activated T-cells) and NF-kappaB (nuclear factor kappaB) via a mechanism that involves diacylglycerol.
Engagement of the B-cell antigen receptor (BCR) induces the activation of various transcription factors, including NFAT (nuclear factor of activated T-cells) and NF-kappaB (nuclear factor kappaB), which participate in long-term biological responses such as proliferation, survival and differentiation of B-lymphocytes. We addressed the biochemical basis of this process using the DT40 chicken B-cell lymphoma. We discovered that Bruton's tyrosine kinase (BTK) and phospholipase C-gamma2 (PLC-gamma2) are required to activate NFAT and NF-kappaB, and to produce the lipid second messenger diacylglycerol in response to BCR cross-linking. Therefore the functional integrity of the BTK/PLC-gamma2/diacylglycerol signalling axis is crucial for BCR-directed activation of both transcription factors NFAT and NF-kappaB.
Antony
P
P
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232-0146, USA.
Petro
J B
JB
Carlesso
G
G
Shinners
N P
NP
Lowe
J
J
Khan
W N
WN
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D002460:Cell Line; D002645:Chickens; D002855:Chromatography, Thin Layer; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004075:Diglycerides / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; D004075:Diglycerides; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011947:Receptors, Antigen, B-Cell; D014157:Transcription Factors; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase