Extracellular signal-regulated kinase 1/2-mediated transcriptional regulation of G-protein-coupled receptor kinase 3 expression in neuronal cells.
J Pharmacol Exp Ther
; 321(1): 51-9, 2007 Apr.
Article
en En
| MEDLINE
| ID: mdl-17255468
ABSTRACT
Relatively small changes in G-protein-coupled receptor kinase (GRK) 3 expression (approximately 2-fold) profoundly affect alpha2-adrenergic receptor (AR) function and preferentially regulate neuronal alpha2A- and alpha2B-AR signaling. In the present study, we provide evidence that epinephrine (EPI)-induced up-regulation of GRK3 protein expression in two neuronal cell lines, BE(2)-C cells (endogenously express alpha2A- and beta2AR) and BN17 cells [endogenously express alpha2B (NG108) and transfected to express beta2-AR] is due in part to increased GRK3 gene expression. In both cell lines, the increase in GRK3 transcription occurred via an extracellular signal-regulated kinase (ERK) 1/2-dependent mechanism because the increase in GRK3 mRNA is eliminated in the presence of the mitogen-activated protein kinase/ERK kinase 1/2 inhibitor, U0126 [1,4-diamino-2,3-dicyano-1,4-bis (2-amino phenylthiobutadiene)]. EPI-induced GRK3 mRNA up-regulation also is prevented in the presence of propranolol or phentolamine. Moreover, GRK3 mRNA did not increase in response to EPI treatment in NG108 cells (endogenously express alpha2B-AR with no beta2-AR). Both these results suggest that simultaneous activation of alpha2- and beta2-AR by EPI is required for the ERK1/2-dependent increase in GRK3 mRNA. The EPI-induced increase in GRK3 mRNA was unaffected in the presence of the protein kinase C inhibitor, chelerythrine chloride. Finally, EPI treatment resulted in increased nuclear translocation and accumulation of the transcription factors, Sp-1 and Ap-2, in BE(2)-C cells. Taken together, our results demonstrate the involvement of the ERK1/2 pathway in selective up-regulation of GRK3 mRNA expression, possibly via activation of Sp-1 and Ap-2 transcription factors in neuronal cells.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Regulación Enzimológica de la Expresión Génica
/
Proteína Quinasa 1 Activada por Mitógenos
/
Proteína Quinasa 3 Activada por Mitógenos
/
Quinasas de Receptores Adrenérgicos beta
/
Neuronas
Límite:
Humans
Idioma:
En
Revista:
J Pharmacol Exp Ther
Año:
2007
Tipo del documento:
Article
País de afiliación:
Estados Unidos