Your browser doesn't support javascript.
loading
The Cool-2/alpha-Pix protein mediates a Cdc42-Rac signaling cascade.
Baird, Dan; Feng, Qiyu; Cerione, Richard A.
Afiliación
  • Baird D; Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA.
Curr Biol ; 15(1): 1-10, 2005 Jan 11.
Article en En | MEDLINE | ID: mdl-15649357
ABSTRACT

BACKGROUND:

Cloned-out of library-2 (Cool-2)/PAK-interactive exchange factor (alpha-Pix) was identified through its ability to bind the Cdc42/Rac target p21-activated kinase (PAK) and has been implicated in certain forms of X-linked mental retardation as well as in growth factor- and chemoattractant-coupled signaling pathways. We recently found that the dimeric form of Cool-2 is a specific guanine nucleotide exchange factor (GEF) for Rac, whereas monomeric Cool-2 is a GEF for Cdc42 as well as Rac. However, unlike many GEFs, Cool-2 binds to activated forms of Cdc42 and Rac. Thus, we have investigated the functional consequences of these interactions.

RESULTS:

We show that the binding of activated Cdc42 to the Cool-2 dimer markedly enhances its ability to associate with GDP bound Rac1, resulting in a significant activation of Rac-GEF activity. While the Rac-specific GEF activity of Cool-2 is mediated through the Dbl homology (DH) domain from one monomer and the Pleckstrin homology domain from the other, activated Cdc42 interacts with the DH domain, most likely opposite the DH domain binding site for GDP bound Rac. Activated Rac also binds to Cool-2; however, it strongly inhibits the GEF activity of dimeric Cool-2.

CONCLUSIONS:

We provide evidence for novel mechanisms of allosteric regulation of the Rac-GEF activity of the Cool-2 dimer, involving stimulatory effects by Cdc42 and feedback inhibition by Rac. These findings demonstrate that by serving as a target for GTP bound Cdc42 and a GEF for Rac, Cool-2 mediates a GTPase cascade where the activation of Cdc42 is translated into the activation of Rac.
Asunto(s)
Buscar en Google
Banco de datos: MEDLINE Asunto principal: Transducción de Señal / Proteínas Serina-Treonina Quinasas / Proteínas de Ciclo Celular / Proteína de Unión al GTP cdc42 / Proteínas de Unión al GTP rac / Factores de Intercambio de Guanina Nucleótido Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Curr Biol Asunto de la revista: BIOLOGIA Año: 2005 Tipo del documento: Article País de afiliación: Estados Unidos
Buscar en Google
Banco de datos: MEDLINE Asunto principal: Transducción de Señal / Proteínas Serina-Treonina Quinasas / Proteínas de Ciclo Celular / Proteína de Unión al GTP cdc42 / Proteínas de Unión al GTP rac / Factores de Intercambio de Guanina Nucleótido Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Curr Biol Asunto de la revista: BIOLOGIA Año: 2005 Tipo del documento: Article País de afiliación: Estados Unidos