Cytokines and Growth factors signal through tyrosine phosphorylation of a family of related transcription factors

Paul Rothman, Brendt Kreider, Mohammad Azam, David Levy, Ursula Wegenka, Andreas Eilers, Thomas Decker, Friedemann Horn, Helena Kashleva, James Ihle, Chris Schindler

Research output: Contribution to journalArticlepeer-review

75 Scopus citations

Abstract

The ability of cytokines to activate distinct but overlapping sets of genes defines their characteristic biological response. We now show that IFNy, IL-3, IL-4, IL-6, erythropoietin, EGF, and CSF-f activate differing members of a family of latent cytoplasmic transcription factors. Although these factors have distinct physical and functional properties and exhibit different patterns of expression, they share many important features, including recognition of a related set of enhancer elements, rapid activation, tyrosine phosphorylation, and cross-reactivity to antibodies against p91, a cytoplasmic signaling protein activated by IFNa, IFNy, and IL-6. These shared features point to either parallel or common patterns of signal transduction. A general model of cytokine signal transduction is presented, in which receptor-associated tyrosine kinases activate ligand-specific members of a family of signal-transducing factors. Once activated, these factors carry their signals to the nucleus, where they bind a family of related enhancer elements.

Original languageEnglish (US)
Pages (from-to)457-468
Number of pages12
JournalImmunity
Volume1
Issue number6
DOIs
StatePublished - Sep 1994
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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