The adapter protein Shc interacts with the interleukin-2 (IL-2) receptor upon IL-2 stimulation

J Biol Chem. 1994 Jan 21;269(3):1599-602.


Binding of interleukin-2 (IL-2) to the IL-2 receptor (IL-2R) stimulates Src family kinases, tyrosine phosphorylation of several proteins, conversion of Ras to its active GTP-bound form, and eventually c-fos, c-jun, and c-myc induction. The IL-2R beta chain plays a crucial role in IL-2R signaling. Within the cytoplasmic domain of the beta chain, a region essential for mitogenesis and another involved in binding the Src family kinase Lck have been defined. The beta chain itself is tyrosine-phosphorylated upon IL-2 stimulation. Since the adapter protein Shc acts upstream of Ras and is involved in T cell receptor-mediated Ras activation, we examined the role of Shc in IL-2 signaling. Shc was found to be tyrosine-phosphorylated upon IL-2 stimulation in CTLL-20 cells. After its phosphorylation, Shc interacted with another adapter protein, Grb2, and, via Grb2, with the Ras GTP/GDP exchange factor mSOS. After IL-2 stimulation, Shc also associated with the IL-2R beta chain. Thus, during IL-2 signaling, the interaction of Shc with the IL-2R beta chain and its simultaneous association with Grb2 and mSOS may couple IL-2R stimulation to Ras signaling.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Animals
  • Cell Line
  • GRB2 Adaptor Protein
  • GTP-Binding Proteins / metabolism
  • Interleukin-2 / pharmacology*
  • Mice
  • Protein Binding
  • Proteins / drug effects
  • Proteins / isolation & purification
  • Proteins / metabolism*
  • Proto-Oncogene Proteins / biosynthesis
  • Proto-Oncogenes
  • Receptors, Interleukin-2 / drug effects
  • Receptors, Interleukin-2 / isolation & purification
  • Receptors, Interleukin-2 / metabolism*
  • Signal Transduction
  • T-Lymphocytes


  • Adaptor Proteins, Signal Transducing
  • GRB2 Adaptor Protein
  • Grb2 protein, mouse
  • Interleukin-2
  • Proteins
  • Proto-Oncogene Proteins
  • Receptors, Interleukin-2
  • GTP-Binding Proteins