Antony P, Petro J B, Carlesso G, Shinners N P, Lowe J, Khan W N
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232-0146, USA.
Biochem Soc Trans. 2004 Feb;32(Pt 1):113-5. doi: 10.1042/bst0320113.
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.
B细胞抗原受体（BCR）的激活会诱导多种转录因子的活化，包括活化T细胞核因子（NFAT）和核因子κB（NF-κB），它们参与B淋巴细胞增殖、存活和分化等长期生物学反应。我们利用DT40鸡B细胞淋巴瘤研究了这一过程的生化基础。我们发现布鲁顿酪氨酸激酶（BTK）和磷脂酶C-γ2（PLC-γ2）是激活NFAT和NF-κB以及在BCR交联时产生脂质第二信使二酰基甘油所必需的。因此，BTK/PLC-γ2/二酰基甘油信号轴的功能完整性对于BCR介导的NFAT和NF-κB这两种转录因子的激活至关重要。
