NEDD4-2 associates with gamma(c) and regulates its degradation rate.
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-2Ralpha, IL-2Rbeta and gamma(c)). Only beta and gamma(c) have been shown to transduce intra cellular signals. The gamma(c) chain is shared by the interleukin-2, 4, 7, 9, 15 and 21 receptors, and is essential for lymphocyte functions. The regulation of gamma(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 gamma(c). And we show that the loss of NEDD4 association on gamma(c) is accompanied by a dramatic increase of the half-life of the receptor subunit.
Malardé
Valérie
V
Institut Pasteur, Unité de Biologie des Interactions Cellulaires, URA CNRS-2582, 75015 Paris, France.
Proust
Richard
R
Dautry-Varsat
Alice
A
Gesbert
Franck
F
D000595:Amino Acid Sequence; D000818:Animals; D056827:Endosomal Sorting Complexes Required for Transport; D006367:HeLa Cells; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit / Q000235:genetics / Q000378:metabolism*; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D000075702:Nedd4 Ubiquitin Protein Ligases; D010766:Phosphorylation; D014443:Tyrosine / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
D056827:Endosomal Sorting Complexes Required for Transport; C507941:IL2RG protein, human; D053631:Interleukin Receptor Common gamma Subunit; D014443:Tyrosine; D000075702:Nedd4 Ubiquitin Protein Ligases; C000618483:Nedd4 protein, human; C000618485:Nedd4L protein, human; C000618461:Nedd4l protein, mouse; D044767:Ubiquitin-Protein Ligases