Cyclic AMP inhibits translation of cyclin D3 in T lymphocytes at the level of elongation by inducing eEF2-phosphorylation.
Cell Signal
; 15(9): 871-81, 2003 Sep.
Article
em En
| MEDLINE
| ID: mdl-12834812
ABSTRACT
The purpose of the present study was to understand the mechanism by which activated protein kinase A (PKA) leads to down-regulation of cyclin D3 in lymphocytes. By using Jurkat cells as a model system, we have been able to demonstrate that cyclin D3 is reduced at the level of translation by inhibition of elongation. One of the important factors involved in translational elongation is the eukaryotic elongation factor 2 (eEF2). eEF2 promotes translation in its unphosphorylated form, and we observed a rapid phosphorylation of the eEF2-protein upon forskolin treatment. When using specific inhibitors of the eEF2-kinase prior to forskolin treatment, we were able to inhibit the increased phosphorylation of eEF2. Furthermore, inhibition of eEF2-kinase prevented the forskolin-mediated down-regulation of cyclin D3. Taken together, it appears that activation of PKA in Jurkat cells reduces the expression of cyclin D3 at the level of translational elongation by increasing the phosphorylation of eEF2 and thereby inhibiting its activity.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Biossíntese de Proteínas
/
Linfócitos T
/
Proteínas Serina-Treonina Quinases
/
Ciclinas
/
Proteínas Quinases Dependentes de Cálcio-Calmodulina
/
AMP Cíclico
/
Fator 2 de Elongação de Peptídeos
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article