Mediation of growth hormone-dependent transcriptional activation by mammary gland factor/stat 5

Timothy J.J. Wood, Daniel Sliva, Peter E. Lobie, Tony J. Pircher, Fabrice Gouilleux, Hiroshi Wakao, Jan Åke Gustafsson, Bernd Groner, Gunnar Norstedt, Lars Arne Haldosén

    Research output: Contribution to journalArticlepeer-review

    164 Scopus citations

    Abstract

    Previous observations have shown that binding of growth hormone to its receptor leads to activation of transcription factors via a mechanism involving phosphorylation on tyrosine residues. In order to establish whether the prolactin-activated transcription factor Stat 5 (mammary gland factor) is also activated by growth hormone, nuclear extracts were prepared from COS-7 cells transiently expressing transfected Stat 5 and growth hormone receptor cDNA. Gel electrophoresis mobility shift analyses revealed the growth hormone-dependent presence of specific DNA-binding proteins in these extracts. The complexes formed could be supershifted by polyclonal anti-Stat 5 antiserum. In other experiments nuclear extracts from growth hormone- treated Chinese hamster ovary cells stably expressing transfected growth hormone receptor cDNA and liver from growth hormone-treated hypophysectomized rats were used for gel electrophoresis mobility shift analyses. These also revealed the presence of specific DNA-binding proteins sharing antigenic determinants with Stat 5. Star 5 cDNA was shown to be capable of complementing the growth hormone-dependent activation of transcription of a reporter gene in the otherwise unresponsive COS-7 cell line. This complementation was dependent on the presence of Stat 5 tyrosine 694, suggesting a role for phosphorylation of this residue in growth hormone- dependent activation of DNA-binding and transcription.

    Original languageEnglish (US)
    Pages (from-to)9448-9453
    Number of pages6
    JournalJournal of Biological Chemistry
    Volume270
    Issue number16
    DOIs
    StatePublished - Apr 21 1995

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Cell Biology

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