Fluid flow activates a regulator of translation, p70/p85 S6 kinase, in human endothelial cells.
Am J Physiol Heart Circ Physiol
; 278(5): H1537-44, 2000 May.
Article
en En
| MEDLINE
| ID: mdl-10775131
ABSTRACT
Cellular phenotype is determined not only by genetic transcription but also by subsequent translation of mRNA into protein. Extracellular signals trigger intracellular pathways that distinctly activate translation. The 70/85-kDa S6 kinase (pp70(S6k)) is a central enzyme in the signal-dependent control of translation, but its regulation in endothelial cells is largely unknown. Here we show that fluid flow (in the absence of an exogenous mitogen) as well as humoral agonists activate endothelial pp70(S6k). Rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR), and wortmannin, a phosphatidylinositol 3-kinase inhibitor, blocked flow-induced pp70(S6k) activation; FK-506, a rapamycin analog with minimal mTOR inhibitory activity, and PD-98059, an inhibitor of the flow-sensitive mitogen-activated protein kinase pathway, had no effect. Synthesis of Bcl-3, a protein whose translation is controlled by an mTOR-dependent pathway, was induced by flow and inhibited by rapamycin and wortmannin. Transcriptional blockade did not abolish the flow-induced upregulation of Bcl-3. Fluid forces may therefore modify endothelial phenotype by specifically regulating translation of certain mRNA transcripts into protein.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Quinasas
/
Factores de Transcripción
/
Velocidad del Flujo Sanguíneo
/
Endotelio Vascular
/
Proteínas Quinasas S6 Ribosómicas
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Am J Physiol Heart Circ Physiol
Asunto de la revista:
CARDIOLOGIA
/
FISIOLOGIA
Año:
2000
Tipo del documento:
Article
País de afiliación:
Estados Unidos