Interaction of STAT5 dimers on two low affinity binding sites mediates interleukin 2 (IL-2) stimulation of IL-2 receptor alpha gene transcription.

Details

Serval ID
serval:BIB_1349
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Interaction of STAT5 dimers on two low affinity binding sites mediates interleukin 2 (IL-2) stimulation of IL-2 receptor alpha gene transcription.
Journal
Journal of Biological Chemistry
Author(s)
Meyer W.K., Reichenbach P., Schindler U., Soldaini E., Nabholz M.
ISSN
0021-9258
Publication state
Published
Issued date
1997
Volume
272
Number
50
Pages
31821-31828
Language
english
Abstract
Stimulation of the interleukin 2 receptor alpha (IL-2Ralpha) gene by IL-2 is important for the proliferation of antigen-activated T lymphocytes. IL-2 regulates IL-2Ralpha transcription via a conserved 51-nucleotide IL-2 responsive enhancer. Mouse enhancer function depends on cooperative activity of three distinct sites. Two of these are weak binding sites for IL-2-activated STAT5 (signal transducer and activator of transcription) proteins, and mutational analysis indicates that binding of STAT5 to both sites is required for IL-2 responsiveness of the enhancer. The STAT5 dimers interact to form a STAT5 tetramer. The efficiency of tetramerization depends on the relative rotational orientation of the two STAT motifs on the DNA helix. STAT5 tetramerization on enhancer mutants correlates well with the IL-2 responsiveness of these mutants. This provides strong evidence that interactions between STAT dimers binding to a pair of weak binding sites play a biological role by controlling the activity of a well characterized, complex cytokine-responsive enhancer.
Keywords
Animals, Base Sequence, Binding Sites, Cell Line, DNA/metabolism, DNA-Binding Proteins/metabolism, Dimerization, Interleukin-2/pharmacology, Mice, Milk Proteins, Molecular Sequence Data, Protein Binding, Receptors, Interleukin-2/genetics, STAT5 Transcription Factor, Trans-Activators/metabolism, Transcription, Genetic
Pubmed
Web of science
Open Access
Yes
Create date
19/11/2007 12:05
Last modification date
20/08/2019 12:41
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