Vav-2 controls NFAT-dependent transcription in B- but not T-lymphocytes
Vav-2 controls NFAT-dependent transcription in B- but not T-lymphocytes
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DOI：
10.1093/emboj/19.22.6173
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发表时间：
2000-11-15
期刊：
影响因子：
11.4
通讯作者：
Turner, M
中科院分区：
文献类型：
--
作者：
Doody, GM;Billadeau, DD;Turner, M
我们发现，在B细胞和T细胞中，Vav-2在抗原受体参与后被酪氨酸磷酸化，但仅在B细胞中增强激活T细胞核因子(NFAT)依赖的转录，Vav-2的功能需要N末端，以及功能DBL同源性和SH2结构域。此外，Vav-2对NFAT依赖转录的增强作用可被许多显性负性GTP酶抑制，Vav-2增强NFAT依赖转录的能力与其促进持续钙通量的能力有关。因此，Vav-2可以增强B细胞中的钙信号，但不能增强T细胞中的钙信号，而截短形式的Vav-2既不能激活NFAT，也不能增强钙信号。CD19共受体与Vav-2在物理上相互作用，协同增强B细胞受体(BCR)诱导的Vav-2的磷酸化，此外，我们还发现Vav-2增强CD19刺激的NFAT依赖的转录，以及CD5增强子的转录。这些数据表明，Vav-2在BCR信号转导到转录因子NFAT中发挥作用，并参与BCR和CD19信号的整合。
We show here that Vav-2 is tyrosine phosphorylated following antigen receptor engagement in both B- and T-cells, but potentiates nuclear factor of activated T cells (NFAT)-dependent transcription only in B cells, Vav-2 function requires the N-terminus, as well as functional Dbl homology and SH2 domains. Moreover, the enhancement of NFAT-dependent transcription by Vav-2 can be inhibited by a number of dominant-negative GTPases, The ability of Vav-2 to potentiate NFAT-dependent transcription correlates with its ability to promote a sustained calcium flux. Thus, Vav-2 augments the calcium signal in B cells but not T cells, and a truncated form of Vav-2 can neither activate NFAT nor augment calcium signaling. The CD19 co-receptor physically interacts with Vav-2 and synergistically enhances Vav-2 phosphorylation induced by the B-cell receptor (BCR), In addition, we found that Vav-2 augments CD19-stimulated NFAT-dependent transcription, as well as transcription from the CD5 enhancer. These data suggest a role for Vav-2 in transducing BCR signals to the transcription factor NFAT and implicate Vav-2 in the integration of BCR and CD19 signaling.