Substrate stiffness governs the initiation of B cell activation by the   concerted signaling of PKC beta and focal adhesion kinase

doi:10.7554/eLife.23060

CORC > 北京大学 > 工学院

	Substrate stiffness governs the initiation of B cell activation by the concerted signaling of PKC beta and focal adhesion kinase
	Shaheen, Samina ; Wan, Zhengpeng ; Li, Zongyu ; Chau, Alicia ; Li, Xinxin ; Zhang, Shaosen ; Liu, Yang ; Yi, Junyang ; Zeng, Yingyue ; Wang, Jing ; Chen, Xiangjun ; Xu, Liling ; Chen, Wei ; Wang, Fei ; Lu, Yun ; Zheng, Wenjie ; Shi, Yan ; Sun, Xiaolin ; Li, Zhanguo ; Xiong, Chunyang ; Liu, Wanli
刊名	ELIFE
	2017
关键词	HIGH EPITOPE DENSITY RHEUMATOID-ARTHRITIS SYNAPSE FORMATION PROTEIN MOLECULE TYROSINE KINASE OUTSIDE-IN C-EPSILON RECEPTOR ANTIGEN INTEGRIN
DOI	10.7554/eLife.23060
英文摘要	The mechanosensing ability of lymphocytes regulates their activation in response to antigen stimulation, but the underlying mechanism remains unexplored. Here, we report that B cell mechanosensing-governed activation requires BCR signaling molecules. PMA-induced activation of PKC beta can bypass the Btk and PLC-gamma 2 signaling molecules that are usually required for B cells to discriminate substrate stiffness. Instead, PKC beta-dependent activation of FAK is required, leading to FAK-mediated potentiation of B cell spreading and adhesion responses. FAK inactivation or deficiency impaired B cell discrimination of substrate stiffness. Conversely, adhesion molecules greatly enhanced this capability of B cells. Lastly, B cells derived from rheumatoid arthritis (RA) patients exhibited an altered BCR response to substrate stiffness in comparison with healthy controls. These results provide a molecular explanation of how initiation of B cell activation discriminates substrate stiffness through a PKC beta-mediated FAK activation dependent manner.; Ministry of Science and Technology of the People's Republic of China [2014CB542500]; National Science Foundation [81422020, 81621002]; SCI(E); ARTICLE; 6
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/471988]
专题	工学院
推荐引用方式 GB/T 7714	Shaheen, Samina,Wan, Zhengpeng,Li, Zongyu,et al. Substrate stiffness governs the initiation of B cell activation by the concerted signaling of PKC beta and focal adhesion kinase[J]. ELIFE,2017.
APA	Shaheen, Samina.,Wan, Zhengpeng.,Li, Zongyu.,Chau, Alicia.,Li, Xinxin.,...&Liu, Wanli.(2017).Substrate stiffness governs the initiation of B cell activation by the concerted signaling of PKC beta and focal adhesion kinase.ELIFE.
MLA	Shaheen, Samina,et al."Substrate stiffness governs the initiation of B cell activation by the concerted signaling of PKC beta and focal adhesion kinase".ELIFE (2017).