The CREB coactivator TORC2 functions as a calcium- and cAMP-sensitive coincidence detector.
Cell
; 119(1): 61-74, 2004 Oct 01.
Article
en En
| MEDLINE
| ID: mdl-15454081
ABSTRACT
Elevations in circulating glucose and gut hormones during feeding promote pancreatic islet cell viability in part via the calcium- and cAMP-dependent activation of the transcription factor CREB. Here, we describe a signaling module that mediates the synergistic effects of these pathways on cellular gene expression by stimulating the dephosphorylation and nuclear entry of TORC2, a CREB coactivator. This module consists of the calcium-regulated phosphatase calcineurin and the Ser/Thr kinase SIK2, both of which associate with TORC2. Under resting conditions, TORC2 is sequestered in the cytoplasm via a phosphorylation-dependent interaction with 14-3-3 proteins. Triggering of the calcium and cAMP second messenger pathways by glucose and gut hormones disrupts TORC214-3-3 complexes via complementary effects on TORC2 dephosphorylation; calcium influx increases calcineurin activity, whereas cAMP inhibits SIK2 kinase activity. Our results illustrate how a phosphatase/kinase module connects two signaling pathways in response to nutrient and hormonal cues.
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Bases de datos:
MEDLINE
Asunto principal:
Fosfoproteínas
/
Transactivadores
/
Proteínas Serina-Treonina Quinasas
/
Proteína de Unión a Elemento de Respuesta al AMP Cíclico
/
AMP Cíclico
/
Calcineurina
/
Señalización del Calcio
Tipo de estudio:
Diagnostic_studies
Idioma:
En
Revista:
Cell
Año:
2004
Tipo del documento:
Article
País de afiliación:
Estados Unidos