LNK (SH2B3) is a key regulator of integrin signaling in endothelial cells and targets α‐parvin to control cell adhesion and migration
| العنوان: | 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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| المؤلفون: | Beéatrice Charreau, Julie Devalliere, Juliette Fitau, Nathalie Gérard, Philippe Hulin, Christopher E. Turner, Laura Velazquez, Mathias Chatelais |
| المصدر: | The FASEB Journal. 26:2592-2606 |
| بيانات النشر: | Wiley, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Cell signaling, Integrin, Protein Serine-Threonine Kinases, Biochemistry, Cell-Matrix Junctions, Research Communications, Focal adhesion, 03 medical and health sciences, 0302 clinical medicine, Cell Movement, Cell Adhesion, Human Umbilical Vein Endothelial Cells, Genetics, Humans, Integrin-linked kinase, Cell adhesion, Molecular Biology, Protein kinase B, Adaptor Proteins, Signal Transducing, 030304 developmental biology, Focal Adhesions, 0303 health sciences, biology, Integrin beta1, Microfilament Proteins, Intracellular Signaling Peptides and Proteins, Proteins, Signal transducing adaptor protein, Cell biology, 030220 oncology & carcinogenesis, biology.protein, Signal transduction, Proto-Oncogene Proteins c-akt, Signal Transduction, Biotechnology |
| الوصف: | 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 β1-integrin-mediated signaling via Akt and GSK3β phosphorylation. Moreover, the α-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 α-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.—Devallière, J., Chatelais, M., Fitau, J., Gérard, N., Hulin, P., Velazquez, L., Turner, C. E. Charreau, B. LNK (SH2B3) is a key regulator of integrin signaling in endothelial cells and targets α-parvin to control cell adhesion and migration. |
| تدمد: | 1530-6860 0892-6638 |
| DOI: | 10.1096/fj.11-193383 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::419a4fc57ef5050722467c07546bf57d https://doi.org/10.1096/fj.11-193383 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....419a4fc57ef5050722467c07546bf57d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15306860 08926638 |
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| DOI: | 10.1096/fj.11-193383 |