BANK1 and BLK act through phospholipase C gamma 2 in B-cell signaling.

BANK1 and BLK act through phospholipase C gamma 2 in B-cell signaling.
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DOI:
10.1371/journal.pone.0059842
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Castillejo-López C
Castillejo-López C
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Bernal-Quirós M;Wu YY;Alarcón-Riquelme ME;Castillejo-López C

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带有锚蛋白重复序列的B细胞适配器蛋白(BANK1)和B淋巴样酪氨酸激酶(BLK)在遗传上与自身免疫有关。在B细胞信号传递过程中,这些基因的蛋白质相互作用,协同工作。人们对它们与其他B细胞信号分子的相互作用或它们在这一过程中的作用知之甚少。利用酵母双杂交(Y2H),我们寻找与BANK1相互作用的因子。我们发现分子开关PLCG2与BANK1相互作用,并且这种相互作用受到B细胞受体(BCR)刺激的促进。我们进一步发现,BLK的激酶活性增强了BANK1-PLCG2的结合,而这种相互作用在BLK耗尽时被抑制。免疫沉淀和突变分析表明,BANK1和PLCG2之间的相互作用依赖于接头蛋白上特定的酪氨酸和脯氨酸残基。我们的结果为理解这两个基因在基础B细胞生理学和免疫相关疾病中的作用提供了重要的新信息。
The B cell adaptor protein with ankyrin repeats (BANK1) and the B lymphoid tyrosine kinase (BLK) have been genetically associated with autoimmunity. The proteins of these genes interact physically and work in concert during B-cell signaling. Little is know about their interactions with other B-cell signaling molecules or their role in the process. Using yeast two hybrid (Y2H) we sought for factors that interact with BANK1. We found that the molecular switch PLCg2 interacts with BANK1 and that the interaction is promoted by B-cell receptor (BCR) stimulation. We found further that the kinase activity of BLK enhanced BANK1- PLCg2 binding and that the interaction was suppressed upon BLK depletion. Immunoprecipitation and mutational analysis demonstrated that the interaction between BANK1 and PLCg2 was dependent on specific tyrosine and proline residues on the adaptor protein. Our results provide new information important to understand the role of these two genes in basic B-cell physiology and immune-related diseases.
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