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

Abstract : 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.
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Contributor : Fabrice Gouilleux Connect in order to contact the contributor
Submitted on : Friday, October 29, 2021 - 5:16:42 PM
Last modification on : Tuesday, May 31, 2022 - 10:20:18 AM
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Signaling through the Il-2 rec...
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S. Gaffen, S. Lai, Wei-Jiang Xu, F. Gouilleux, B. Groner, et al.. Signaling through the interleukin 2 receptor beta chain activates a STAT-5-like DNA-binding activity.. 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⟩. ⟨hal-02427574⟩



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