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

Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7192-6. doi: 10.1073/pnas.92.16.7192.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Binding Sites
  • Cell Line
  • DNA / genetics
  • DNA / metabolism*
  • DNA-Binding Proteins / metabolism*
  • Interleukin-2 / metabolism
  • Interleukin-2 / pharmacology
  • Mice
  • Milk Proteins*
  • Molecular Sequence Data
  • Peptide Fragments / chemistry
  • Peptide Fragments / genetics
  • Peptide Fragments / pharmacology
  • Phosphotyrosine
  • Receptors, Interleukin-2 / chemistry
  • Receptors, Interleukin-2 / genetics
  • Receptors, Interleukin-2 / metabolism*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • STAT5 Transcription Factor
  • Signal Transduction
  • Trans-Activators / metabolism*
  • Tyrosine / analogs & derivatives
  • Tyrosine / chemistry
  • Tyrosine / genetics


  • DNA-Binding Proteins
  • Interleukin-2
  • Milk Proteins
  • Peptide Fragments
  • Receptors, Interleukin-2
  • Recombinant Fusion Proteins
  • STAT5 Transcription Factor
  • Trans-Activators
  • Phosphotyrosine
  • Tyrosine
  • DNA