Different interleukin 2 receptor beta-chain tyrosines couple to at least two signaling pathways and synergistically mediate interleukin 2-induced proliferation

Proc Natl Acad Sci U S A. 1996 Mar 5;93(5):2077-82. doi: 10.1073/pnas.93.5.2077.


One of the earliest events induced by interleukin 2 (IL-2) is tyrosine phosphorylation of cellular proteins, including the IL-2 receptor beta chain (IL-2Rbeta). Simultaneous mutation of three tyrosines (Y338, Y392, and Y510) in the IL-2Rbeta cytoplasmic domain abrogated IL-2-induced proliferation, whereas mutation of only Y338 or of Y392 and Y510 inhibited proliferation only partially. While Y392 and Y510 were critical for IL-2-induced activation of signal transducers and activators of transcription (STAT proteins), Y338 was required for Shc-IL-2Rbeta association and for IL-2-induced tyrosine phosphorylation of Shc. Thus, activation of both Jak-STAT and Shc-coupled signaling pathways requires specific IL-2Rbeta tyrosines that together act in concert to mediate maximal proliferation. In COS-7 cells, overexpression of Jak1 augmented phosphorylation of Y338 as well as Y392 and Y510, suggesting that the role for this Jak kinase may extend beyond the Jak-STAT pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Adaptor Proteins, Vesicular Transport*
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cells, Cultured
  • Chlorocebus aethiops
  • DNA-Binding Proteins / metabolism
  • Humans
  • Janus Kinase 1
  • Lymphocyte Activation*
  • Mice
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Phosphotyrosine / chemistry
  • Protein Binding
  • Protein-Tyrosine Kinases / metabolism
  • Proteins / metabolism
  • Receptor Aggregation
  • Receptors, Interleukin-2 / chemistry
  • Receptors, Interleukin-2 / physiology*
  • STAT1 Transcription Factor
  • Shc Signaling Adaptor Proteins
  • Signal Transduction*
  • Src Homology 2 Domain-Containing, Transforming Protein 1
  • T-Lymphocytes / physiology*
  • Trans-Activators / metabolism
  • Tyrosine / chemistry


  • Adaptor Proteins, Signal Transducing
  • Adaptor Proteins, Vesicular Transport
  • DNA-Binding Proteins
  • Proteins
  • Receptors, Interleukin-2
  • SHC1 protein, human
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • Shc Signaling Adaptor Proteins
  • Shc1 protein, mouse
  • Src Homology 2 Domain-Containing, Transforming Protein 1
  • Stat1 protein, mouse
  • Trans-Activators
  • Phosphotyrosine
  • Tyrosine
  • Protein-Tyrosine Kinases
  • JAK1 protein, human
  • Jak1 protein, mouse
  • Janus Kinase 1