دورية أكاديمية
CD28 utilizes Vav-1 to enhance TCR-proximal signaling and NF-AT activation
| العنوان: | CD28 utilizes Vav-1 to enhance TCR-proximal signaling and NF-AT activation |
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| المؤلفون: | F. Michel, G. Attal Bonnefoy, A. Alcover, A. Roumier, D. Olive, O. Acuto, MANGINO, GIORGIO, TUOSTO, Loretta |
| المساهمون: | F., Michel, Mangino, Giorgio, G., Attal Bonnefoy, Tuosto, Loretta, A., Alcover, A., Roumier, D., Olive, O., Acuto |
| بيانات النشر: | AMER ASSOC IMMUNOLOGISTS |
| سنة النشر: | 2000 |
| المجموعة: | Sapienza Università di Roma: CINECA IRIS |
| الوصف: | The mechanism through which CD28 costimulation potentiates TCR-driven gene expression is still not clearly defined. Vav-1, an exchange factor for Rho GTPases thought to regulate, mainly through Rac-1, various signaling components leading to cytokine gene expression, is tyrosine phosphorylated upon CD28 engagement. Here, we provide evidence for a key role of Vav-1 in CD28-mediated signaling. Overexpression of Vav-1 in Jurkat cells in combination with CD28 ligation strongly reduced the concentration of staphylococcus enterotoxin E/MHC required for TCR-induced NF-AT activation. Surprisingly, upon Vav-1 overexpression CD28 ligation sufficed to activate NF-AT in the absence of TCR engagement. This effect was not mediated by overexpression of ZAP-70 nor of SLP-76 but necessitated the intracellular tail of CD28, the intactness of the TCR-proximal signaling cascade, the Src-homology domain 2 (SH2) domain of Vav-1, and SLP-76 phosphorylation, an event which was favored by Vav-1 itself. Cells overexpressing Vav-1 formed lamellipodia and microspikes reminiscent of Rac-1 and Cdc42 activation, respectively, for which the SH2 domain of Vav-1 was dispensable. Together, these data suggest that CD28 engagement activates Vav-1 to boost TCR signals through a synergistic cooperation between Vav-1 and SLP-76 and probably via cortical actin changes to facilitate the organization of a signaling zone. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | ELETTRONICO |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/11034388; info:eu-repo/semantics/altIdentifier/wos/WOS:000089477500037; volume:165; issue:7; firstpage:3820; lastpage:3829; numberofpages:10; journal:JOURNAL OF IMMUNOLOGY; http://hdl.handle.net/11573/362518Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-0034292369; http://www.jimmunol.org/content/165/7/3820.longTest |
| DOI: | 10.4049/jimmunol.165.7.3820 |
| الإتاحة: | https://doi.org/10.4049/jimmunol.165.7.3820Test http://hdl.handle.net/11573/362518Test http://www.jimmunol.org/content/165/7/3820.longTest |
| رقم الانضمام: | edsbas.2DDC1012 |
| قاعدة البيانات: | BASE |
| DOI: | 10.4049/jimmunol.165.7.3820 |
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