Transcription factor p91 interacts with the epidermal growth factor receptor and mediates activation of the c-fos gene promoter.
Transcription factor p91 contains a SH2 domain and is activated by tyrosine phosphorylation. Here we demonstrate that epidermal growth factor (EGF) induces rapid tyrosine phosphorylation and nuclear translocation of p91. Through its SH2 domain, p91 directly interacts with the EGF receptor in a ligand-dependent manner. p91 is a necessary component of an EGF-induced DNA-binding factor that recognizes a previously identified regulatory element, SIE (c-sis-inducible element), in the c-fos gene promoter. Activated p91 stimulates SIE-dependent transcription in vitro. Cotransfection of an SIE-containing reporter with a p91 expression vector shows that p91 is a positive transcriptional regulator of the c-fos gene promoter. These studies suggest that EGF uses a direct signaling pathway to control nuclear transcriptional events.
Fu
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Department of Biochemistry, Mount Sinai School of Medicine, New York, New York 10029.
Zhang
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D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D016762:Genes, fos; D006801:Humans; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009838:Oligodeoxyribonucleotides; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012333:RNA, Messenger / Q000302:isolation & purification / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000378:metabolism*; D014404:Tubulin / Q000096:biosynthesis
D004268:DNA-Binding Proteins; C494227:IRF9 protein, human; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014157:Transcription Factors; D014404:Tubulin; D004815:Epidermal Growth Factor; D066246:ErbB Receptors