RSK phosphorylates SOS1 creating 14-3-3-docking sites and negatively regulating MAPK activation.
Biochem J
; 447(1): 159-66, 2012 Oct 01.
Article
en En
| MEDLINE
| ID: mdl-22827337
ABSTRACT
The extent and duration of MAPK (mitogen-activated protein kinase) signalling govern a diversity of normal and aberrant cellular outcomes. Genetic and pharmacological disruption of the MAPK-activated kinase RSK (ribosomal S6 kinase) leads to elevated MAPK activity indicative of a RSK-dependent negative feedback loop. Using biochemical, pharmacological and quantitative MS approaches we show that RSK phosphorylates the Ras activator SOS1 (Son of Sevenless homologue 1) in cultured cells on two C-terminal residues, Ser(1134) and Ser(1161). Furthermore, we find that RSK-dependent SOS1 phosphorylation creates 14-3-3-binding sites. We show that mutating Ser(1134) and Ser(1161) disrupts 14-3-3 binding and modestly increases and extends MAPK activation. Together these data suggest that one mechanism whereby RSK negatively regulates MAPK activation is via site-specific SOS1 phosphorylation.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Quinasas S6 Ribosómicas
/
Sistema de Señalización de MAP Quinasas
/
Proteína SOS1
/
Proteínas 14-3-3
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Biochem J
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos