Tyrosine phosphorylation of DNA binding proteins by multiple cytokines

Andrew C. Larner*, Michael David, Gerald M. Feldman, Ken Ichi Igarashi, Rebecca H. Hackett, Deborah S.A. Webb, Sharon M. Sweitzer, Emanuel F. Petricoin, David S. Finbloom

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

366 Scopus citations


Interferon-α (IFN-α) and IFN-γ 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 Fcγ receptor gene (FcγRI). 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-γ response region (GRR) located in the promoter of the FcγRI 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-γ or IL-10 contained p91. Instead, complexes activated by IL-3 or GM-CSF contained a tyrosine-phosphorylated protein of 80 kilodaltons. Induction of FcγRI RNA occurred only with IFN-γ and IL-10, whereas pretreatment of cells with GM-CSF or IL-3 inhibited IFN-γ induction of FcγRI RNA. Thus, several cytokines other than interferons can activate putative transcription factors by tyrosine phosphorylation.

Original languageEnglish
Pages (from-to)1730-1733
Number of pages4
Issue number5129
StatePublished - 1993
Externally publishedYes


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