The Gab1 scaffold regulates RTK-dependent dorsal ruffle formation through the adaptor Nck.
J Cell Sci
; 123(Pt 8): 1306-19, 2010 Apr 15.
Article
en En
| MEDLINE
| ID: mdl-20332103
ABSTRACT
The polarised distribution of signals downstream from receptor tyrosine kinases (RTKs) regulates fundamental cellular processes that control cell migration, growth and morphogenesis. It is poorly understood how RTKs are involved in the localised signalling and actin remodelling required for these processes. Here, we show that the Gab1 scaffold is essential for the formation of a class of polarised actin microdomain, namely dorsal ruffles, downstream from the Met, EGF and PDGF RTKs. Gab1 associates constitutively with the actin-nucleating factor N-WASP. Following RTK activation, Gab1 recruits Nck, an activator of N-WASP, into a signalling complex localised to dorsal ruffles. Formation of dorsal ruffles requires interaction between Gab1 and Nck, and also requires functional N-WASP. Epithelial cells expressing Gab1DeltaNck (Y407F) exhibit decreased Met-dependent Rac activation, fail to induce dorsal ruffles, and have impaired cell migration and epithelial remodelling. These data show that a Gab1-Nck signalling complex interacts with several RTKs to promote polarised actin remodelling and downstream biological responses.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Fosfoproteínas
/
Proteínas Oncogénicas
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Proteínas Tirosina Quinasas Receptoras
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Extensiones de la Superficie Celular
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Proteínas Adaptadoras Transductoras de Señales
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Cell Sci
Año:
2010
Tipo del documento:
Article
País de afiliación:
Canadá