Tyrosine phosphorylation of DNA binding proteins by multiple cytokines.
Interferon-alpha (IFN-alpha) and IFN-gamma regulate gene expression by tyrosine phosphorylation of several transcription factors that have the 91-kilodalton (p91) protein of interferon-stimulated gene factor-3 (ISGF-3) as a common component. Interferon-activated protein complexes bind enhancers present in the promoters of early response genes such as the high-affinity Fc gamma receptor gene (Fc gamma RI). Treatment of human peripheral blood monocytes or basophils with interleukin-3 (IL-3), IL-5, IL-10, or granulocyte-macrophage colony-stimulating factor (GM-CSF) activated DNA binding proteins that recognized the IFN-gamma response region (GRR) located in the promoter of the Fc gamma RI gene. Although tyrosine phosphorylation was required for the assembly of each of these GRR binding complexes, only those formed as a result of treatment with IFN-gamma or IL-10 contained p91. Instead, complexes activated by IL-3 or GM-CSF contained a tyrosine-phosphorylated protein of 80 kilodaltons. Induction of Fc gamma RI RNA occurred only with IFN-gamma and IL-10, whereas pretreatment of cells with GM-CSF or IL-3 inhibited IFN-gamma induction of Fc gamma RI RNA. Thus, several cytokines other than interferons can activate putative transcription factors by tyrosine phosphorylation.
Larner
A C
AC
Division of Cytokine Biology, Center for Biologics Evaluation and Research, Bethesda, MD 20892.
David
M
M
Feldman
G M
GM
Igarashi
K
K
Hackett
R H
RH
Webb
D S
DS
Sweitzer
S M
SM
Petricoin
E F
EF
Finbloom
D S
DS
D001483:Base Sequence; D016207:Cytokines / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D016753:Interleukin-10 / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism; D050794:STAT1 Transcription Factor; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
D016207:Cytokines; D004268:DNA-Binding Proteins; D007377:Interleukin-3; D007378:Interleukins; D017452:Receptors, IgG; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D016753:Interleukin-10; D014443:Tyrosine; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor