cAMP cascade leads to Ras activation in cortical neurons.
Brain Res Mol Brain Res
; 75(1): 54-60, 2000 Jan 10.
Article
en En
| MEDLINE
| ID: mdl-10648887
Monoaminergic G protein-coupled receptors (GPCRs) are highly expressed in the CNS at the cerebrocortical level, where they support a variety of behavioural responses. To elucidate possible intracellular signalling pathways coupled to these receptors, we have studied their ability to activate extracellular signal-regulated kinases (ERKs) in cultured cortical neurons. An increase in ERK activity was observed after stimulation of neurons with dopamine or serotonin, and with agonists selective for various GPCRs. In addition, ERK activation was also observed following treatment with phorbol dibutyrate (PdBu) and forskolin, activators of protein kinase C (PKC) and protein kinase A (PKA), respectively. Concomitant with ERK activation, all the monoaminergic agonists tested also increased the level of active Ras (Ras-GTP). Surprisingly, Ras activation was also observed after activation of cAMP pathway, and this effect was at least in part mediated by PKA. Ras activation by cAMP was unique for neurons, since in PC12 cells forskolin caused activation of ERK but did not increase Ras-GTP level. These results highlight the relevance of Ras as a target for multiple signalling cascades leading to activation of the ERK pathway in neurons.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Corteza Cerebral
/
AMP Cíclico
/
Proteínas ras
/
Proteínas Quinasas Activadas por Mitógenos
/
Neuronas
Límite:
Animals
Idioma:
En
Revista:
Brain Res Mol Brain Res
Asunto de la revista:
BIOLOGIA MOLECULAR
/
CEREBRO
Año:
2000
Tipo del documento:
Article
País de afiliación:
Italia
Pais de publicación:
Países Bajos