NEDD4-2 associates with γ_c and regulates its degradation rate

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• 作者：Valé ; rie Malardé ; Richard Proust ; Alice Dautry-Varsat ; Franck Gesbert
• 关键词：Cytokine ; Receptor ; Ubiquitin ligase ; Signaling ; Degradation ; Lymphocyte ; NEDD4 ; IL-2
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2009
• 出版时间：18 September 2009
• 年：2009
• 卷：387
• 期：2
• 页码：409-413
• 全文大小：1121 K

文摘

Interleukin-2 (IL-2) is a cytokine that regulates proliferation, differentiation and survival of various lymphoid cell subsets. Its actions are mediated through its binding to the IL-2 receptor which is composed of three subunits (IL-2Rα, IL-2Rβ and γ_c). Only β and γ_c have been shown to transduce intra cellular signals. The γ_c chain is shared by the interleukin-2, 4, 7, 9, 15 and 21 receptors, and is essential for lymphocyte functions. The regulation of γ_c expression level is therefore critical for the ability of cells to respond to these cytokines. In the present work, we show that the IL-2R constitutively associates with the ubiquitin ligase NEDD4-2, and to a lesser extent NEDD4-1. We identified the specific binding site on γ_c. And we show that the loss of NEDD4 association on γ_c is accompanied by a dramatic increase of the half-life of the receptor subunit.