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Signaling through the interleukin 2 receptor beta chain activates a STAT-5-like DNA-binding activity

Authors :
Warner C. Greene
Weiduan Xu
Bernd Groner
Fabrice Gouilleux
Sarah L. Gaffen
Stephen Y. Lai
Mark A. Goldsmith
Gladstone Institute of Virology and Immunology
University of California [San Francisco] (UCSF)
University of California-University of California
Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501)
Université de Tours
Goethe-Universität Frankfurt am Main
Université de Tours (UT)
Source :
Proceedings of the National Academy of Sciences of the United States of America, Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 1995, 92 (16), pp.7192-7196. ⟨10.1073/pnas.92.16.7192⟩
Publication Year :
1995
Publisher :
HAL CCSD, 1995.

Abstract

International audience; To explore the possible involvement of STAT factors ("signal transducers and activators of transcription") in the interleukin 2 receptor (IL-2R) signaling cascade, murine HT-2 cells expressing chimeric receptors composed of the extracellular domain of the erythropoietin receptor fused to the cytoplasmic domains of the IL-2R beta or -gamma c chains were prepared. Erythropoietin or IL-2 activation of these cells resulted in rapid nuclear expression of a DNA-binding activity that reacted with select STAT response elements. Based on reactivity with specific anti-STAT antibodies, this DNA-binding activity was identified as a murine homologue of STAT-5. Induction of nuclear expression of this STAT-5-like factor was blocked by the addition of herbimycin A, a tyrosine kinase inhibitor, but not by rapamycin, an immunophilin-binding antagonist of IL-2-induced proliferation. The IL-2R beta chain appeared critical for IL-2-induced activation of STAT-5, since a mutant beta chain lacking all cytoplasmic tyrosine residues was incapable of inducing this DNA binding. In contrast, a gamma c mutant lacking all of its cytoplasmic tyrosine residues proved fully competent for the induction of STAT-5. Physical binding of STAT-5 to functionally important tyrosine residues within IL-2R beta was supported by the finding that phosphorylated, but not nonphosphorylated, peptides corresponding to sequences spanning Y392 and Y510 of the IL-2R beta tail specifically inhibited STAT-5 DNA binding.

Details

Language :
English
ISSN :
00278424 and 10916490
Database :
OpenAIRE
Journal :
Proceedings of the National Academy of Sciences of the United States of America, Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 1995, 92 (16), pp.7192-7196. ⟨10.1073/pnas.92.16.7192⟩
Accession number :
edsair.doi.dedup.....f1de5f9b6e1670fac0c307627c08e438
Full Text :
https://doi.org/10.1073/pnas.92.16.7192⟩