Ligand-induced activation of ERK1/2 signaling by constitutively active Gs-coupled 5-HT receptors.
Acta Pharmacol Sin
; 40(9): 1157-1167, 2019 Sep.
Article
em En
| MEDLINE
| ID: mdl-30833707
ABSTRACT
5-HT4R, 5-HT6R, and 5-HT7AR are three constitutively active Gs-coupled 5-HT receptors that have key roles in brain development, learning, memory, cognition, and other physiological processes in the central nervous system. In addition to Gs signaling cascade mediated by these three 5-HT receptors, the ERK1/2 signaling which is dependent on cyclic adenosine monophosphate (cAMP) production and protein kinase A (PKA) activation downstream of Gs signaling has also been widely studied. In this study, we investigated these two signaling pathways originating from the three Gs-coupled 5-HT receptors in AD293 cells. We found that the phosphorylation and activation of ERK1/2 are ligand-induced, in contrast to the constitutively active Gs signaling. This indicates that Gs signaling alone is not sufficient for ERK1/2 activation in these three 5-HT receptors. In addition to Gs, we found that ß-arrestin and Fyn are essential for the activation of ERK1/2. Together, these results put forth a novel mechanism for ERK1/2 activation involving the cooperative action of Gs, ß-arrestin, and Fyn.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Proteína Quinase 1 Ativada por Mitógeno
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Receptores 5-HT4 de Serotonina
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Proteína Quinase 3 Ativada por Mitógeno
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article