Functional cross-talk between angiotensin II and epidermal growth factor receptors in NIH3T3 fibroblasts.
J Hypertens
; 20(4): 693-9, 2002 Apr.
Article
em En
| MEDLINE
| ID: mdl-11910305
ABSTRACT
BACKGROUND:
The main angiotensin (Ang) II subtype receptors (AT1R and AT2R) are involved in cellular growth processes and exert functionally antagonistic effects.OBJECTIVE:
To characterize the mechanisms by which Ang II receptors influence growth, by investigating the interactions between Ang II subtype receptors and epidermal growth factor (EGF) receptors on mitogen-activated protein kinase (MAPK) pathway activation. DESIGN ANDMETHODS:
The experiments were performed using a mouse fibroblast cell line, NIH3T3, by transient co-transfection with rat AT1R or AT2R expression vectors, or both. Extracellular-signal-regulated kinase (ERK)1/2 phosphorylation was analysed by western blot and the ERK activity was evaluated using PathDetect, an in-vivo signal transduction pathway trans-reporting system. Selective Ang II receptor antagonists (losartan for AT1R and PD123319 for AT2R) were used to investigate the contributions of each receptor to the response observed.RESULTS:
Our data show that, in this cellular model, both Ang II receptors phosphorylate ERK1/2. However, in the cells expressing AT1R, the EGF-induced MAPK pathway was enhanced in the presence of Ang II in a synergistic fashion. In contrast, a reduction of EGF-induced MAPK activation was observed in the cells expressing AT2R. In cells expressing both Ang II subtype receptors, Ang II promoted an enhancement of EGF-induced MAPK activation. However, in the presence of the AT1R antagonist, losartan, the effect of EGF was reduced.CONCLUSION:
These data indicate the existence of an opposite cross-talk of AT1R and AT2R with EGF receptors, and suggest a complex functional interaction between these pathways in the regulation of cellular growth processes.
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Base de dados:
MEDLINE
Assunto principal:
Receptores de Angiotensina
/
Receptores ErbB
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2002
Tipo de documento:
Article