Interferon-dependent tyrosine phosphorylation of a latent cytoplasmic transcription factor.
The interferon-alpha (IFN-alpha)-stimulated gene factor 3 (ISGF3), a transcriptional activator, contains three proteins, termed ISGF3 alpha proteins, that reside in the cell cytoplasm until they are activated in response to IFN-alpha. Treatment of cells with IFN-alpha caused these three proteins to be phosphorylated on tyrosine and to translocate to the cell nucleus where they stimulate transcription through binding to IFN-alpha-stimulated response elements in DNA. IFN-gamma, which activates transcription through a different receptor and different DNA binding sites, also caused tyrosine phosphorylation of one of these proteins. The ISGF3 alpha proteins may be substrates for one or more kinases activated by ligand binding to the cell surface and may link occupation of a specific polypeptide receptor with activation of transcription of a set of specific genes.
Schindler
C
C
Laboratory of Molecular Cell Biology, Rockefeller University, New York, NY 10021.
Shuai
K
K
Prezioso
V R
VR
Darnell
J E
JE
D002462:Cell Membrane / Q000502:physiology; D002467:Cell Nucleus / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006801:Humans; D050832:Interferon-Stimulated Gene Factor 3; D050833:Interferon-Stimulated Gene Factor 3, alpha Subunit; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D016898:Interferon-alpha / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology; D008715:Methionine / Q000378:metabolism; D008954:Models, Biological; D008970:Molecular Weight; D010748:Phosphopeptides / Q000302:isolation & purification; D010766:Phosphorylation; D011480:Protease Inhibitors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D014157:Transcription Factors / Q000302:isolation & purification / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects*; D014443:Tyrosine
D004268:DNA-Binding Proteins; C494227:IRF9 protein, human; D050832:Interferon-Stimulated Gene Factor 3; D050833:Interferon-Stimulated Gene Factor 3, alpha Subunit; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D016898:Interferon-alpha; D010748:Phosphopeptides; D011480:Protease Inhibitors; D014157:Transcription Factors; D014443:Tyrosine; D007371:Interferon-gamma; D008715:Methionine; D011505:Protein-Tyrosine Kinases