Wild-type NRas and KRas perform distinct functions during transformation.
Mol Cell Biol
; 27(19): 6742-55, 2007 Oct.
Article
en En
| MEDLINE
| ID: mdl-17636015
ABSTRACT
The ras proto-oncogenes, of which there are four isoforms, are molecular switches that function in signal transduction pathways to control cell differentiation, proliferation, and survival. How the Ras isoforms orchestrate cellular processes that affect behavior is poorly understood. Further, why cells express two or more Ras isoforms is unknown. Here, using a genetically defined system, we show that the presence of both wild-type KRas and NRas isoforms is required for transformation because they perform distinct nonoverlapping functions wild-type NRas regulates adhesion, and KRas coordinates motility. Remarkably, we find that Ras isoforms achieve functional specificity by engaging different signaling pathways to affect the same cellular processes, thereby coordinating cellular outcome. Although we find that signaling from both isoforms intersects in actin and microtubule cytoskeletons, our results suggest that KRas signals through Akt and Cdc42 while NRas signals through Raf and RhoA. Our analyses suggest a previously unappreciated convergence of different Ras isoforms on the dynamics of the processes involved in transformation.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Transducción de Señal
/
Transformación Celular Neoplásica
/
Proteínas Proto-Oncogénicas p21(ras)
/
Genes ras
/
Isoenzimas
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Mol Cell Biol
Año:
2007
Tipo del documento:
Article
País de afiliación:
Estados Unidos