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Prolactin, growth hormone, erythropoietin and granulocyte-macrophage colony stimulating factor induce MGF-Stat5 DNA

F Gouilleux1, C Pallard, I Dusanter-Fourt

  • 1Institute for Experimental Cancer Research, Tumor Biology Center, Freiburg, Germany.

The EMBO Journal
|May 1, 1995
PubMed

Insights

Signal transducers and activators of transcription (Stat) proteins, like MGF-Stat5, are activated by janus kinases (Jak). MGF-Stat5 mediates prolactin, erythropoietin (EPO), and growth hormone (GH) signaling, impacting mammary and hematopoietic cells.

Area of Science:

  • Cellular signaling pathways
  • Molecular biology
  • Transcription factors

Background:

  • Cytokine signaling involves janus kinases (Jak) and signal transducers and activators of transcription (Stat) proteins.
  • Stat proteins are activated by tyrosine phosphorylation, potentially by Jak kinases.
  • MGF-Stat5 is a Stat protein linked to prolactin response.

Purpose of the Study:

  • To investigate the role of MGF-Stat5 in cytokine signaling.
  • To determine which cytokines activate MGF-Stat5 and the mechanism involved.
  • To explore the physiological relevance of MGF-Stat5 in different cell types.

Main Methods:

  • Transfection of COS cells with receptor and MGF-Stat5 vectors.
  • Assessing MGF-Stat5 DNA binding activity upon stimulation with prolactin, EPO, and GH.
  • Investigating transcriptional induction using a beta-casein promoter luciferase construct.
  • Analyzing MGF-Stat5 related factors in UT7 cells treated with EPO and GM-CSF.

Main Results:

  • Prolactin, EPO, and GH stimulate MGF-Stat5 DNA binding activity.
  • Activation requires phosphorylation of tyrosine residue 694 on MGF-Stat5.
  • Transcriptional induction by prolactin is specific; EPO and GH do not induce it.
  • EPO and GM-CSF activate a MGF-Stat5 related factor in hematopoietic cells.

Conclusions:

  • MGF-Stat5 is activated by multiple cytokines, including prolactin, EPO, and GH.
  • Specific tyrosine phosphorylation at residue 694 is crucial for MGF-Stat5 activation.
  • MGF-Stat5 plays a role in both mammary epithelial and hematopoietic cell functions.

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