Antiproliferative action of interferon-α requires components of T- cell-receptor signalling

  • E. F. Petricoin
  • , S. Ito
  • , B. L. Williams
  • , S. Audet
  • , L. F. Stancato
  • , A. Gamero
  • , K. Clouse
  • , P. Grimley
  • , A. Weiss
  • , J. Beeler
  • , D. S. Finbloom
  • , E. W. Shores
  • , R. Abraham
  • , A. C. Larner

Research output: Contribution to journalArticlepeer-review

141 Scopus citations

Abstract

Signal transduction through both cytokine and lymphocyte antigen receptors shares some common pathways by which they initiate cellular responses, such as activation of mitogen-activated protein kinase(s). However, other signalling components appear to be uniquely coupled to each receptor. For example, the interferon receptors transduce regulatory signals through the JAK/STAT pathway, resulting in an inhibition of growth and of antiviral effects, whereas this pathway apparently plays no role in T-cell- receptor (TCR)-dependent gene expression. Conversely, signal transduction through the TCR requires the tyrosine kinases Lck and ZAP-70 and the tyrosine phosphatase CD45 (ref. 5). Here we show that, unexpectedly, transmission of growth-inhibitory signals by interferon-α (IFN-α) in T cells requires the expression and association of CD45, Lck and ZAP-70 with the IFN-α-receptor signalling complex.

Original languageEnglish
Pages (from-to)629-632
Number of pages4
JournalNature
Volume390
Issue number6660
DOIs
StatePublished - 1997

Keywords

  • Animals
  • Chlorocebus aethiops
  • DNA-Binding Proteins/metabolism
  • Growth Inhibitors/metabolism
  • Humans
  • In Vitro Techniques
  • Interferon-alpha/metabolism
  • Jurkat Cells
  • Leukocyte Common Antigens/metabolism
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/metabolism
  • Measles virus/drug effects
  • Protein-Tyrosine Kinases/metabolism
  • Receptor, Interferon alpha-beta
  • Receptors, Antigen, T-Cell/metabolism
  • Receptors, Interferon/metabolism
  • STAT1 Transcription Factor
  • STAT2 Transcription Factor
  • Signal Transduction
  • Trans-Activators/metabolism
  • Vero Cells
  • Virus Replication/drug effects
  • ZAP-70 Protein-Tyrosine Kinase

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