In vitro activation of the transcription factor ISGF3 by interferon α involves a membrane-associated tyrosine phosphatase and tyrosine kinase

M. David, G. Romero, Z. Y. Zhang, J. E. Dixon, A. C. Larner

Research output: Contribution to journalArticle

73 Scopus citations

Abstract

Interaction of interferon α (IFNα) with its cell surface receptor rapidly activates the formation of the transcription complex ISGF3, which subsequently translocates to the nucleus and stimulates the expression of a variety of early response genes. We have recently developed a cell-free system where IFNα can activate the formation of ISGF3 in vitro. This system has enabled us to demonstrate that the component of the ISGF3 transcription complex which is modified by IFNα treatment (ISGF3α) is membrane-associated and that its activation involves a protein kinase. Using a combination of specific tyrosine kinase and phosphatase inhibitors and monoclonal anti- phosphotyrosine antibodies we now are able to demonstrate that IFNα- activated transcription involves at least a two-step process where a membrane-associated tyrosine phosphatase and a tyrosine kinase lead to modification of ISGF3α and subsequent formation of the complete complex. Furthermore, formation of the ISGF3 complex is specifically disrupted by protein tyrosine phosphatase and can be reversibly dissociated by the phosphotyrosine analogue phenylphosphate. The latter observation suggested that SH2 and/or SH3 domains may be required for the stable formation of this transcription complex.

Original languageEnglish (US)
Pages (from-to)6593-6599
Number of pages7
JournalJournal of Biological Chemistry
Volume268
Issue number9
StatePublished - Jan 1 1993
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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