Identification of a variable region within the cytoplasmic tail of the IL-2 receptor beta chain that is required for growth signal transduction

J Biol Chem. 1995 Sep 22;270(38):22176-81. doi: 10.1074/jbc.270.38.22176.


Interleukin-2 (IL-2) regulates numerous biological events, including T lymphocyte proliferation. Interleukin-2 receptor (IL-2R)-mediated signaling is triggered by ligand-induced heterodimerization of the IL-2R beta and gamma c subunits, which results in the activation of signaling intermediates that are associated with either IL-2R beta or gamma c. Previous mutagenesis studies of the IL-2R beta cytoplasmic tail demonstrated that the partially conserved box 1 and box 2 motifs and specific tyrosine residues are critical for growth signaling. By deletion and alanine scanning mutagenesis, another set of residues that are critical for IL-2R-mediated signaling has now been identified. These residues lie within the divergent 35-amino acid "spacer" region separating box 1 and box 2. The role of this receptor subregion in early phases of IL-2R signaling was evaluated using BA/F3 stable cell lines expressing three functionally impaired mutants from this region. All three cell lines displayed substantially diminished growth responsiveness to IL-2. Receptor-mediated STAT factor activation, IL-2R beta phosphorylation, and Janus kinase activation were also markedly impaired. These findings indicate that this variable spacer region, which we have termed the V-box, is essential for the initiation of IL-2R-mediated signal transduction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cells, Cultured
  • DNA-Binding Proteins / metabolism
  • In Vitro Techniques
  • Interleukin-2 / physiology*
  • Janus Kinase 1
  • Janus Kinase 3
  • Mice
  • Milk Proteins*
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Phosphorylation
  • Phosphotyrosine
  • Protein-Tyrosine Kinases / metabolism
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptors, Interleukin-2 / chemistry*
  • Receptors, Interleukin-2 / metabolism
  • STAT5 Transcription Factor
  • Signal Transduction
  • Structure-Activity Relationship
  • Trans-Activators / metabolism
  • Tyrosine / analogs & derivatives
  • Tyrosine / metabolism


  • DNA-Binding Proteins
  • Interleukin-2
  • Milk Proteins
  • Receptors, Interleukin-2
  • STAT5 Transcription Factor
  • Trans-Activators
  • Phosphotyrosine
  • Tyrosine
  • Protein-Tyrosine Kinases
  • Receptor Protein-Tyrosine Kinases
  • Jak1 protein, mouse
  • Jak3 protein, mouse
  • Janus Kinase 1
  • Janus Kinase 3