The Rab GTPase-activating protein AS160 as a common regulator of insulin- and Galphaq-mediated intracellular GLUT4 vesicle distribution.
Endocr J
; 56(3): 345-59, 2009.
Article
em En
| MEDLINE
| ID: mdl-19139597
ABSTRACT
Akt substrate of 160kDa (AS160) is a Rab GTPase activating protein (GAP) and was recently identified as a component of the insulin signaling pathway of glucose transporter type 4 (GLUT4) translocation. We and others, previously reported that the activation of Galphaq protein-coupled receptors (GalphaqPCRs) also stimulated GLUT4 translocation and glucose uptake in several cell lines. Here, we report that the activation of GalphaqPCRs also promoted phosphorylation of AS160 by the 5'-AMP activated protein kinase (AMPK). The suppression of AS160 phosphorylation by the siRNA mediated AMPKalpha1 subunit knockdown promoted GLUT4 vesicle retention in intracellular compartments. This suppression did not affect the ratio of non-induced cell surface GLUT4 to Galphaq-induced it. Rat 3Y1 cells lacking AS160 did not show insulin-induced GLUT4 translocation. The cells stably expressing GLUT4 revealed GLUT4 vesicles that were mainly localized in the perinuclear region and less frequently on the cell surface. After expression of exogenous AS160, GLUT4 on the cell surface decreased and GLUT4 vesicles were redistributed throughout the cytoplasm. Although PMA-induced or sodium fluoride-induced GLUT4 translocation was significantly increased in these cells, insulin did not affect GLUT4 translocation. These results suggest that AS160 is a common regulator of insulin- and GalphaqPCR activation-mediated GLUT4 distribution in the cells.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Ativadoras de GTPase
/
Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP
/
Transportador de Glucose Tipo 4
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Endocr J
Assunto da revista:
ENDOCRINOLOGIA
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Japão