Growth effects of alpha-interferon but not of bombesin or angiotensin II are mediated by activation of STAT proteins.
Eur J Clin Invest
; 28(5): 398-406, 1998 May.
Article
in En
| MEDLINE
| ID: mdl-9650014
ABSTRACT
BACKGROUND:
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Angiotensin II
/
Bombesin
/
Trans-Activators
/
Interferon-alpha
/
DNA-Binding Proteins
/
Growth Inhibitors
Limits:
Animals
/
Humans
Language:
En
Journal:
Eur J Clin Invest
Year:
1998
Document type:
Article
Affiliation country:
Switzerland