WIP provides an essential link between Nck and N-WASP during Arp2/3-dependent actin polymerization.
Curr Biol
; 23(11): 999-1006, 2013 Jun 03.
Article
en En
| MEDLINE
| ID: mdl-23707428
ABSTRACT
Nck links phosphotyrosine-based signaling to Arp2/3-dependent actin polymerization during many different cellular processes as well as actin-based motility of enteropathogenic Escherichia coli (EPEC), vaccinia, and other vertebrate poxviruses by interacting with N-WASP/WASP. Nck also binds WASP-interacting protein (WIP), which inhibits the ability of N-WASP to activate the Arp2/3 complex until it receives an appropriate signaling input. Using mouse embryonic fibroblasts (MEFs) lacking Nck, WIP, or N-WASP, we have investigated whether an interaction of Nck with both WIP and N-WASP is required for their recruitment to vaccinia during Arp2/3-dependent actin assembly. We find that WIP or its homolog WIRE is required for N-WASP recruitment and actin-based motility of the virus. WIP contains two Nck-binding sites and is recruited to the virus, bound to N-WASP, by interacting with the second SH3 domain of Nck. N-WASP also contains two Nck-binding sites, but its recruitment is dependent on its interaction with WIP rather than Nck. The first and third SH3 domains of Nck are not required to recruit the WIPN-WASP complex but are essential to stimulate actin assembly. We have established that WIP acts as an essential link between Nck and N-WASP. Our observations provide important insights into the hierarchy and connections in one of the major cellular signaling networks stimulating Arp2/3 complex-dependent actin polymerization.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Virus Vaccinia
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Proteínas Portadoras
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Actinas
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Proteínas Oncogénicas
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Proteínas Adaptadoras Transductoras de Señales
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Complejo 2-3 Proteico Relacionado con la Actina
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Proteína Neuronal del Síndrome de Wiskott-Aldrich
Límite:
Animals
Idioma:
En
Revista:
Curr Biol
Asunto de la revista:
BIOLOGIA
Año:
2013
Tipo del documento:
Article
País de afiliación:
Reino Unido