The IL-2 receptor complex: its structure, function, and target genes

Annu Rev Immunol. 1993;11:245-68. doi: 10.1146/annurev.iy.11.040193.001333.

Abstract

Proliferation of T lymphocytes is triggered by the interaction of IL-2 with its specific receptor following T lymphocyte activation. The receptor for IL-2 consists of at least three distinct subunits, the alpha chain (IL-2R alpha), the beta chain (IL-2R beta), and the gamma chain (IL-2R gamma). Although the role of IL-2R gamma in IL-2 signalling remains unclear, IL-2R beta is the subunit critical for receptor-mediated signalling. Because IL-2R beta lacks any apparent catalytic motifs, IL-2R beta may be physically or functionally coupled to other signalling molecules. Structure-function studies of IL-2R beta have revealed that at least two distinct cytoplasmic regions of IL-2R beta are involved in IL-2-induced cellular signalling. The "serine-rich" region of IL-2R beta was identified as a region critical for IL-2-induced mitotic signalling from experiments in which IL-2R beta mutant cDNAs lacking a particular cytoplasmic region or regions were expressed in an IL-3-dependent mouse pro-B cell line (BAF-B03). Meanwhile, another cytoplasmic region of IL-2R beta, the "acidic" region, is responsible for its physical association with an src-family protein tyrosine kinase (PTK), p56lck and is critical for activating the p56lck PTK following IL-2 stimulation. It is now evident that IL-2R beta is linked to at least two intracellular signalling pathways that mediate nuclear proto-oncogene induction. One pathway is linked to tyrosine phosphorylation events, mediated by a src-family protein tyrosine kinase (PTK), and that pathway leads to the induction of the c-fos, c-jun, and other genes of this family. Another pathway leads to c-myc gene induction by an as yet unknown mechanism. We discuss the complex signalling machinery that links the cell surface receptor to the nuclear events.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Molecular Structure
  • Multigene Family
  • Protein-Tyrosine Kinases / immunology
  • Proto-Oncogenes
  • Receptors, Immunologic / genetics
  • Receptors, Interleukin-2 / chemistry*
  • Receptors, Interleukin-2 / genetics
  • Receptors, Interleukin-2 / physiology
  • Signal Transduction / immunology

Substances

  • Receptors, Immunologic
  • Receptors, Interleukin-2
  • Protein-Tyrosine Kinases