التفاصيل البيبلوغرافية
| العنوان: |
The signalling factor PI3K is a specific regulator of the clathrin-independent dynamin-dependent endocytosis of IL-2 receptors. |
| المؤلفون: |
Basquin, Cyril, Malarde, Valérie, Mellor, Paul, Anderson, Deborah H., Meas-Yedid, Vannary, Olivo-Marin, Jean-Christophe, Dautry-Varsat, Alice, Sauvonnet, Nathalie |
| المصدر: |
Journal of Cell Science; 3/1/2013, Vol. 126 Issue 5, p1099-1108, 10p |
| مصطلحات موضوعية: |
CELLULAR signal transduction, CLATHRIN, ENDOCYTOSIS, INTERLEUKIN-2 receptors, GENE expression, BIOCHEMISTRY |
| مستخلص: |
Receptor-mediated endocytosis is an essential process used by eukaryotic cells to internalise many molecules. Several clathrinindependent endocytic routes exist, but the molecular mechanism of each pathway remains to be uncovered. The present study focuses on a clathrin-independent dynamin-dependent pathway used by interleukin 2 receptors (IL-2R), essential players of the immune response. Ras-related C3 botulinum toxin substrate (Rac1) and its targets, the p21-activated kinases (Pak), are specific regulators of this pathway, acting on cortactin and actin polymerization. The present study reveals a dual and specific role of phosphatidylinositol 3-kinase (PI3K) in IL-2R endocytosis. Inhibition of the catalytic activity of PI3K strongly affects IL-2R endocytosis, in contrast to transferrin (Tf) uptake, a marker of the clathrin-mediated pathway. Moreover, Vav2, a GTPase exchange factor (GEF) induced upon PI3K activation, is specifically involved in IL-2R entry. The second action of PI3K is through its regulatory subunit, p85α, which binds to and recruits Rac1 during IL-2R internalisation. Indeed, the overexpression of a p85α mutant missing the Rac1 binding motif leads to the specific inhibition of IL-2R endocytosis. The inhibitory effect of this p85α mutant could be rescued by the overexpression of either Rac1 or the active form of Pak, indicating that p85α acts upstream of the Rac1-Pak cascade. Finally, biochemical and fluorescent microscopy techniques reveal an interaction between p85α, Rac1 and IL-2R that is enhanced by IL-2. In summary, our results indicate a key role of class I PI3K in IL- 2R endocytosis that creates a link with IL-2 signalling. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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