Cytoplasmic Domains of the interleukin-2 Receptor Beta and Gamma Chains Mediate the Signal for T-cell Proliferation

Nature. 1994 May 26;369(6478):333-6. doi: 10.1038/369333a0.

Abstract

The interleukin-2 receptor (IL-2R) consists of three distinct chains (alpha, beta, gamma) which bind IL-2 and generate a proliferative signal in T cells. To define the mechanism of receptor activation, chimaeric receptors were constructed from the intracellular region of either IL-2R beta or IL-2R gamma and the extracellular region of c-kit, a receptor tyrosine kinase that homodimerizes on binding stem cell factor (SCF). We report here that binding of SCF to the beta-chain chimaera induced proliferation of the pro-B-cell line BA/F3, but not T cells. But in T cells expressing both the beta- and gamma-chain chimaeras, SCF induced proliferation and tyrosine phosphorylation characteristic of the native IL-2R signal. Chimaeric IL-2 receptor beta and gamma chains constructed with the heterodimeric extracellular regions of the granulocyte-macrophage colony stimulating factor receptor (GM-CSFR) also provided the IL-2R signal. Thus, heterodimerization of the cytoplasmic domains of IL-2R beta and -gamma appears necessary and sufficient for signalling in T cells.

MeSH terms

  • Animals
  • B-Lymphocytes / physiology
  • Base Sequence
  • Biopolymers
  • Cell Line
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Hematopoietic Cell Growth Factors / metabolism
  • Humans
  • Lymphocyte Activation / immunology
  • Mice
  • Molecular Sequence Data
  • Phosphorylation
  • Proto-Oncogene Proteins / physiology
  • Proto-Oncogene Proteins c-kit
  • Receptor Protein-Tyrosine Kinases / physiology
  • Receptors, Colony-Stimulating Factor / physiology
  • Receptors, Interleukin-2 / chemistry*
  • Receptors, Interleukin-2 / physiology*
  • Recombinant Fusion Proteins
  • Signal Transduction / immunology*
  • Stem Cell Factor
  • T-Lymphocytes / physiology*
  • Tyrosine / metabolism

Substances

  • Biopolymers
  • Hematopoietic Cell Growth Factors
  • Proto-Oncogene Proteins
  • Receptors, Colony-Stimulating Factor
  • Receptors, Interleukin-2
  • Recombinant Fusion Proteins
  • Stem Cell Factor
  • Tyrosine
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Proto-Oncogene Proteins c-kit
  • Receptor Protein-Tyrosine Kinases