LNK (SH2B3) is a key regulator of integrin signaling in endothelial cells and targets α-parvin to control cell adhesion and migration
LNK (SH2B3) is a key regulator of integrin signaling in endothelial cells and targets α-parvin to control cell adhesion and migration
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DOI：
10.1096/fj.11-193383
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发表时间：
2012-06-01
期刊：
影响因子：
4.8
通讯作者：
Charreau, Beatrice
中科院分区：
文献类型：
--
作者：
Devalliere, Julie;Chatelais, Mathias;Charreau, Beatrice
Focal adhesion (FA) formation and disassembly play an essential role in adherence and migration of endothelial cells. These processes are highly regulated and involve various signaling molecules that are not yet completely identified. Lnk [Src homology 2-B3 (SH2B3)] belongs to a family of SH2-containing proteins with important adaptor functions. In this study, we showed that Lnk distribution follows that of vinculin, localizing Lnk in FAs. Inhibition of Lnk by RNA interference resulted in decreased spreading, whereas sustained expression dramatically increases the number of focal and cell-matrix adhesions. We demonstrated that Lnk expression impairs FA turnover and cell migration and regulates beta 1-integrin-mediated signaling via Akt and GSK3 beta phosphorylation. Moreover, the alpha-parvin protein was identified as one of the molecular targets of Lnk responsible for impaired FA dynamics and cell migration. Finally, we established the ILK protein as a new molecular partner for Lnk and proposed a model in which Lnk regulates alpha-parvin expression through its interaction with ILK. Collectively, our results underline the adaptor Lnk as a novel and effective key regulator of integrin-mediated signaling controlling endothelial cell adhesion and migration.-Devalliere, J., Chatelais, M., Fitau, J., Gerard, N., Hulin, P., Velazquez, L., Turner, C. E. Charreau, B. LNK (SH2B3) is a key regulator of integrin signaling in endothelial cells and targets alpha-parvin to control cell adhesion and migration. FASEB J. 26, 2592-2606 (2012). www.fasebj.org
