title: Cytokines and growth factors signal through tyrosine phosphorylation of a family of related transcription factors.
abstract: The ability of cytokines to activate distinct but overlapping sets of genes defines their characteristic biological response. We now show that IFN gamma, IL-3, IL-4, IL-6, erythropoietin, EGF, and CSF-1 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 IFN alpha, IFN gamma, 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.
authors.affiliation: Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
authors.forename: P
authors.initials: P
authors.lastname: Rothman
authors.forename: B
authors.initials: B
authors.lastname: Kreider
authors.forename: M
authors.initials: M
authors.lastname: Azam
authors.forename: D
authors.initials: D
authors.lastname: Levy
authors.forename: U
authors.initials: U
authors.lastname: Wegenka
authors.forename: A
authors.initials: A
authors.lastname: Eilers
authors.forename: T
authors.initials: T
authors.lastname: Decker
authors.forename: F
authors.initials: F
authors.lastname: Horn
authors.forename: H
authors.initials: H
authors.lastname: Kashleva
authors.forename: J
authors.initials: J
authors.lastname: Ihle
mesh_terms: D001483:Base Sequence; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006133:Growth Substances / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D012045:Regulatory Sequences, Nucleic Acid; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D016207:Cytokines; D004268:DNA-Binding Proteins; D006133:Growth Substances; D014157:Transcription Factors; D011505:Protein-Tyrosine Kinases