Induction of interleukin-2 receptor alpha (IL-2Ralpha) expression by interleukin-2: important role of the interleukin-2 receptor beta chain region between the two Stat5 docking sites.

Details

Serval ID
serval:BIB_23595
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Induction of interleukin-2 receptor alpha (IL-2Ralpha) expression by interleukin-2: important role of the interleukin-2 receptor beta chain region between the two Stat5 docking sites.
Journal
European Cytokine Network
Author(s)
Imbert V., Rezzonico R., Reichenbach P., Nabholz M.
ISSN
1148-5493 (Print)
ISSN-L
1148-5493
Publication state
Published
Issued date
2002
Volume
13
Number
3
Pages
331-339
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
The interleukin-2 receptor alpha (IL-2Ralpha) forms, together with IL-2Rbeta and gammac chains, a high affinity IL-2 receptor that is important for IL-2 responsiveness and normal T cell function. Expression of the IL-2Ralpha gene by T cells is regulated mainly at the transcription level which is transiently activated by antigen and upregulated and then prolonged by stimulation with IL-2. The effect of IL-2 on the IL-2Ralpha gene depends on the activation of the transcription factor Stat5, which acts on an IL-2- responsive enhancer that consists of two Stat5 and an Elf1 binding site. To identify the functional domains of the IL-2 receptor required for the stimulation of IL-2Ralpha gene expression, we introduced, into the CTL44 T cell line, receptor chimeras between the extracellular domain of the IL-9 receptor and the cytoplasmic region of IL-2Rbeta. Analyzing the effect of mutations in the intracellular IL-2Rbeta segment, we found that a minimal receptor containing the Jak boxes and one intact Stat5 docking site (i.e. tyrosine 392 or 510) can, as expected, mediate Stat5 activation, but is unable to stimulate IL-2Ralpha expression. However, when this minimal receptor includes the region between the two tyrosines, its capacity to mediate IL-2Ralpha cell surface expression is restored. These data suggest that the segment between the two Stat5 docking sites of the IL-2Rbeta chain mediates signaling events that, together with Stat5 activation, are essential for the stimulation of IL-2Ralpha gene transcription.
Keywords
Animals, Base Sequence, Blotting, Western, Cell Line, DNA Primers, DNA-Binding Proteins/metabolism, Electrophoretic Mobility Shift Assay, Interleukin-2/physiology, Interleukin-2 Receptor alpha Subunit, Interleukin-2 Receptor beta Subunit, Mice, Milk Proteins, Precipitin Tests, Protein Binding, Receptors, Interleukin/genetics, Receptors, Interleukin/physiology, STAT5 Transcription Factor, Trans-Activators/metabolism
Pubmed
Create date
19/11/2007 12:19
Last modification date
20/08/2019 13:01
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