Angiotensin II AT1 receptor mutants expressed in CHO cells caused morphological change and inhibition of cell growth.
Regul Pept
; 131(1-3): 18-22, 2005 Nov.
Article
em En
| MEDLINE
| ID: mdl-15967516
To assess the importance of the leucine residues in positions 262 and 265 of the angiotensin AT(1) receptor for signaling pathways and receptor expression and regulation, we compared the properties of CHO cells transfected with the wild type or the L262D or L265D receptor point mutants. It was found that the two mutants significantly increased the basal intracellular cyclic AMP (cAMP) formation in an agonist-independent mode. The morphology transformation of CHO cells was correlated with the increased cAMP formation, since forskolin, a direct activator of adenylate cyclase mimicked this effect on WT-expressing CHO cells. DNA synthesis was found to be inhibited in these cell lines, indicating that cAMP may also have determined the inhibitory effect on cell growth, in addition to the cell transformation from a tumorigenic to a non-tumorigenic phenotype. However a role for an increased Ca2+ influx induced by the mutants in non-stimulated cells cannot be ruled out since this ion also was shown to cause transformed cells to regain the morphology and growth regulation.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptor Tipo 1 de Angiotensina
/
Proliferação de Células
/
Forma Celular
Limite:
Animals
Idioma:
En
Revista:
Regul Pept
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Brasil
País de publicação:
Holanda