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Growth effects of alpha-interferon but not of bombesin or angiotensin II are mediated by activation of STAT proteins.

AbstractBACKGROUND:
The recently discovered Jak/STAT signal transduction pathway is associated with cytokine or growth factor receptors; whether members of the G protein-coupled receptor superfamily also activate this pathway is not yet clear. As a first member, the angiotensin (AT)1A receptor has been demonstrated to phosphorylate Jak and STAT proteins. Bombesin, a neurotransmitter and growth factor in many cells and tissues, activates its G protein-coupled receptor and in addition phosphorylates proteins that might be members of the Jak/STAT family. This study investigated whether bombesin- or angiotensin-mediated growth effects are associated with STAT protein activation.
METHODS:
Functional receptors were characterized using ligand-binding studies, second-messenger activation and determination of ligand-mediated growth effects. STAT protein activation was analysed by electrophoretic mobility shift assay (EMSA) using labelled DNA response elements recognizing all known STAT proteins.
RESULTS:
Functional bombesin receptors mediating mitogenic effects were demonstrated on Swiss 3T3 fibroblasts, human melanoma cells (A375-6) and primary human lung fibroblasts; however, bombesin-related STAT protein activation was not observed by EMSA. Interferon-alpha typically activated a STAT1-STAT2-p48 heterotrimer, as well as STAT1-3 hetero- and homodimers in human melanoma cells and significantly inhibited growth of this cell line in vitro. Functional AT1A receptors on primary rat cardiac fibroblasts mediated angiotensin-stimulated growth effects but, in contrast to recently published data, did not activate any known STAT protein.
CONCLUSION:
Interferon alpha-stimulated growth inhibition is mediated by activation of the Jak/STAT pathway, whereas bombesin or AT1A receptor-mediated effects on cellular proliferation do not involve phosphorylation of STAT proteins.
AuthorsA Pansky, P Hildebrand, M H Heim, M Eberhard, T Kissel, C Beglinger
JournalEuropean journal of clinical investigation (Eur J Clin Invest) Vol. 28 Issue 5 Pg. 398-406 (May 1998) ISSN: 0014-2972 [Print] England
PMID9650014 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • DNA-Binding Proteins
  • Growth Inhibitors
  • Interferon-alpha
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • STAT2 Transcription Factor
  • STAT2 protein, human
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Stat1 protein, mouse
  • Stat1 protein, rat
  • Stat2 protein, mouse
  • Stat3 protein, mouse
  • Stat3 protein, rat
  • Trans-Activators
  • Angiotensin II
  • Bombesin
Topics
  • 3T3 Cells
  • Angiotensin II (pharmacology)
  • Animals
  • Bombesin (pharmacology)
  • Cell Division (drug effects)
  • DNA-Binding Proteins (metabolism)
  • Fibroblasts (drug effects)
  • Growth Inhibitors (pharmacology)
  • Humans
  • Interferon-alpha (pharmacology)
  • Lung (cytology)
  • Melanoma (pathology)
  • Mice
  • Myocardium (cytology)
  • Rats
  • STAT1 Transcription Factor
  • STAT2 Transcription Factor
  • STAT3 Transcription Factor
  • Signal Transduction (drug effects)
  • Trans-Activators (metabolism)
  • Tumor Cells, Cultured

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