Assembly of high order G alpha q-effector complexes with RGS proteins.
J Biol Chem
; 283(50): 34923-34, 2008 Dec 12.
Article
en En
| MEDLINE
| ID: mdl-18936096
Transmembrane signaling through G alpha(q)-coupled receptors is linked to physiological processes such as cardiovascular development and smooth muscle function. Recent crystallographic studies have shown how G alpha(q) interacts with two activation-dependent targets, p63RhoGEF and G protein-coupled receptor kinase 2 (GRK2). These proteins bind to the effector-binding site of G alpha(q) in a manner that does not appear to physically overlap with the site on G alpha(q) bound by regulator of G-protein signaling (RGS) proteins, which function as GTPase-activating proteins (GAPs). Herein we confirm the formation of RGS-G alpha(q)-GRK2/p63RhoGEF ternary complexes using flow cytometry protein interaction and GAP assays. RGS2 and, to a lesser extent, RGS4 are negative allosteric modulators of Galpha(q) binding to either p63RhoGEF or GRK2. Conversely, GRK2 enhances the GAP activity of RGS4 but has little effect on that of RGS2. Similar but smaller magnitude responses are induced by p63RhoGEF. The fact that GRK2 and p63RhoGEF respond similarly to these RGS proteins supports the hypothesis that GRK2 is a bona fide G alpha(q) effector. The results also suggest that signal transduction pathways initiated by GRK2, such as the phosphorylation of G protein-coupled receptors, and by p63RhoGEF, such as the activation of gene transcription, can be regulated by RGS proteins via both allosteric and GAP mechanisms.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas RGS
/
Factores de Intercambio de Guanina Nucleótido
/
Subunidades alfa de la Proteína de Unión al GTP Gq-G11
/
Quinasa 2 del Receptor Acoplado a Proteína-G
Límite:
Humans
Idioma:
En
Revista:
J Biol Chem
Año:
2008
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos