Cytokines and growth factors signal through tyrosine phosphorylation of a family of related transcription factors.
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.
Rothman
P
P
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
Kreider
B
B
Azam
M
M
Levy
D
D
Wegenka
U
U
Eilers
A
A
Decker
T
T
Horn
F
F
Kashleva
H
H
Ihle
J
J
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*
D016207:Cytokines; D004268:DNA-Binding Proteins; D006133:Growth Substances; D014157:Transcription Factors; D011505:Protein-Tyrosine Kinases