AKT2 deficiency impairs formation of the BCR signalosome

AKT2 deficiency impairs formation of the BCR signalosome
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AKT2 缺陷会损害 BCR 信号体的形成

DOI:
10.1186/s12964-020-00534-9
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发表时间:
2020-04
影响因子:
8.4
通讯作者:
Yongjie Zhang
Yongjie Zhang
中科院分区:
生物学2区
文献类型:
--
作者:
Zuochen Du;Di Yang;Yongjie Zhang

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背景:Akt2是参与胰岛素诱导的信号转导和肿瘤发生发展的关键分子之一。方法:本研究采用AKT2基因敲除小鼠模型,研究AKT2在BCR信号转导和B细胞分化中的作用。结果:Akt2通过促进BCR信号转导和肌动蛋白重塑,促进B细胞的早期激活。AKT2 KO小鼠B细胞在体外受刺激后出现缺陷铺展和bcr聚集现象。Btk介导的信号转导中断导致生发中心B细胞分化受损,免疫AKT2 KO小鼠血清特异性IgM和IgG水平降低。此外,在AKT2 KO小鼠中,肌动蛋白聚合调节因子WASP的激活水平降低,也影响了肌动蛋白的重塑。作为B细胞活化早期bcr信号和肌动蛋白重塑的重要调节因子,在AKT2缺失的B细胞中,CD19的磷酸化水平降低,而转录水平正常。结论:Akt2参与体液反应,促进bcr信号和肌动蛋白重塑,通过调节CD19磷酸化增强B细胞的活化。
Background: AKT2 is one of the key molecules that involves in the insulin-induced signaling and the development.of cancer. In B cells, the function of AKT2 is unclear..Methods: In this study, we used AKT2 knockout mice model to study the role of AKT2 in BCR signaling and B cell.differentiation..Results: AKT2 promotes the early activation of B cells by enhancing the BCR signaling and actin remodeling. B cells.from AKT2 KO mice exhibited defective spreading and BCR clustering upon stimulation in vitro. Disruption of.Btk-mediated signaling caused the impaired differentiation of germinal center B cells, and the serum levels of both.sepecific IgM and IgG were decreased in the immunized AKT2 KO mice. In addition, the actin remodeling was.affected due to the decreased level of the activation of WASP, the actin polymerization regulator, in AKT2 KO mice.as well. As a crucial regulator of both BCR signaling and actin remodeling during early activation of B cells, the.phosphorylation of CD19 was decreased in the AKT2 absent B cells, while the transcription level was normal..Conclusions: AKT2 involves in the humoral responses, and promotes the BCR signaling and actin remodeling to.enhance the activation of B cells via regulating CD19 phosphorylation
DOI: 10.1093/pcmedi/pbac012
发表时间: 2022-05-13
影响因子: 5.3
作者:
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DOI: 10.1007/s11515-013-1272-0
发表时间: 2013-10
期刊: Frontiers in biology
影响因子: --
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DOI: 10.1016/j.cmet.2017.10.008
发表时间: 2018-01-09
期刊: Cell metabolism
影响因子: 29
作者:
Sanchez-Gurmaches J;Tang Y;Jespersen NZ;Wallace M;Martinez Calejman C;Gujja S;Li H;Edwards YJK;Wolfrum C;Metallo CM;Nielsen S;Scheele C;Guertin DA
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DOI: 10.1074/jbc.m302847200
发表时间: 2003-08-22
影响因子: 4.8
作者:
Yang, ZZ;Tschopp, O;Hemmings, BA
通讯作者: Hemmings, BA
DOI: 10.1096/fj.14-262097
发表时间: 2015-02-01
期刊: FASEB JOURNAL
影响因子: 4.8
作者:
Rotllan, Noemi;Chamorro-Jorganes, Aranzazu;Fernandez-Hernando, Carlos
通讯作者: Fernandez-Hernando, Carlos