Modulation of the activation of Stat1 by the interferon-gamma receptor complex

Christopher D. Krause, Wen He, Sergei Kotenko, Sidney Pestka

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


The activation of Stat1 by the interferon-gamma (IFN-γ) receptor complex is responsible for the transcription of a significant portion of IFN-γ induced genes. Many of these genes are responsible for the induction of an apoptotic state in response to IFN-γ. In the absence of Stat1 activation, IFN-γ instead induces a proliferative response. Modifying Stat1 activation by IFN-γ may have pharmacological benefits. We report that the rate of activation of Stat1 can be altered in HeLa cells by overexpressing either the IFN-γR1 chain or the IFN-γR2 chain. These alterations occur in hematopoietic cell lines: Raji cells and monocytic cell lines, which have average and above-average IFN-γR2 surface expression, activate Stat1 similarly to HeLa cells and HeLa cells overexpressing IFNγR2, respectively. The rapid Stat1 activation seen in HeLa cells can be inhibited by overexpressing a chimeric IFN-γR2 chain that does not bind Jak2 or (when high concentrations of IFN-γ are used) by overexpressing IFN-γR1. These data are consistent with a model in which the recruitment of additional Jak2 activity to a signaling complex accelerates the rate of Stat1 activation. We conclude that the rate of activation of Stat1 in cells by IFN-γ can be modified by regulating either receptor chain and speculate that pharmacological agents which modify receptor chain expression may alter IFN-γ receptor signal transduction.

Original languageEnglish (US)
Pages (from-to)113-123
Number of pages11
JournalCell Research
Issue number1
StatePublished - Jan 19 2006

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology


  • Electrophoretic mobility shift assay
  • Interferon-gamma
  • Interferon-gamma receptor
  • Kinetics
  • Stat1

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