Cyclin-dependent kinase 5 promotes proteasomal degradation of the 5-HT1A receptor via phosphorylation.
Biochem Biophys Res Commun
; 510(3): 370-375, 2019 03 12.
Article
en En
| MEDLINE
| ID: mdl-30712943
ABSTRACT
Serotonin (5-HT) is a major neurotransmitter in mammalian brains and is involved in brain development and psychiatric disorders. The 5-HT1A receptor (5-HT1AR) is a G-protein-coupled receptor (GPCR) associated with an inhibitory G-protein (Gi) with the widest and most abundant expression. It is not known; however, how expression or activity of 5-HTlAR is regulated. We studied here phosphorylation of 5-HT1AR by cyclin-dependent kinase 5 (Cdk5), a neuron-specific membrane-bound Ser/Thr kinase that is activated by binding of the p35 Cdk5 activator. 5-HT1AR was phosphorylated by the Cdk5-p35 complex at Thr314 in the third cytoplasmic loop. The phosphorylation stimulated the degradation of 5-HT1AR by the proteasome, resulting in neutralization of the inhibitory action of 5-HT1AR on intracellular cAMP concentration. These results suggest that Cdk5-p35 modulates 5-HT signaling through phosphorylation-dependent degradation of 5-HTlAR.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Receptor de Serotonina 5-HT1A
/
Complejo de la Endopetidasa Proteasomal
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Quinasa 5 Dependiente de la Ciclina
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2019
Tipo del documento:
Article
País de afiliación:
Japón