Preassembly and ligand-induced restructuring of the chains of the IFN-gamma receptor complex: the roles of Jak kinases, Stat1 and the receptor chains

Cell Res. 2006 Jan;16(1):55-69. doi: 10.1038/sj.cr.7310008.

Abstract

We previously demonstrated using noninvasive technologies that the interferon-gamma (IFN-gamma) receptor complex is preassembled (1). In this report we determined how the receptor complex is preassembled and how the ligand-mediated conformational changes occur. The interaction of Stat1 with IFN-gammaR1 results in a conformational change localized to IFN-gammaR1. Jak1 but not Jak2 is required for the two chains of the IFN-gamma receptor complex (IFN-gammaR1 and IFN-gammaR2) to interact; however, the presence of both Jak1 and Jak2 is required to see any ligand-dependant conformational change. Two IFN-gammaR2 chains interact through species-specific determinants in their extracellular domains. Finally, these determinants also participate in the interaction of IFN-gammaR2 with IFN-gammaR1. These results agree with a detailed model of the IFN-gamma receptor that requires the receptor chains to be pre-associated constitutively for the receptor to be active.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Animals
  • COS Cells
  • Chlorocebus aethiops
  • Humans
  • Janus Kinase 1
  • Janus Kinase 2
  • Ligands
  • Models, Biological
  • Molecular Sequence Data
  • Mutagenesis
  • Protein Conformation
  • Protein-Tyrosine Kinases / physiology*
  • Proto-Oncogene Proteins / physiology*
  • Receptors, Interferon / chemistry*
  • Receptors, Interferon / genetics
  • Receptors, Interferon / metabolism*
  • STAT1 Transcription Factor / metabolism
  • STAT1 Transcription Factor / physiology*
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Transfection

Substances

  • Ligands
  • Proto-Oncogene Proteins
  • Receptors, Interferon
  • STAT1 Transcription Factor
  • interferon gamma receptor
  • Protein-Tyrosine Kinases
  • JAK1 protein, human
  • JAK2 protein, human
  • Janus Kinase 1
  • Janus Kinase 2