RCP-driven α5ß1 recycling suppresses Rac and promotes RhoA activity via the RacGAP1-IQGAP1 complex.
J Cell Biol
; 202(6): 917-35, 2013 Sep 16.
Article
en En
| MEDLINE
| ID: mdl-24019536
Inhibition of αvß3 or expression of mutant p53 promotes invasion into fibronectin (FN)-containing extracellular matrix (ECM) by enhancing Rab-coupling protein (RCP)-dependent recycling of α5ß1 integrin. RCP and α5ß1 cooperatively recruit receptor tyrosine kinases, including EGFR1, to regulate their trafficking and downstream signaling via protein kinase B (PKB)/Akt, which, in turn, promotes invasive migration. In this paper, we identify a novel PKB/Akt substrate, RacGAP1, which is phosphorylated as a consequence of RCP-dependent α5ß1 trafficking. Phosphorylation of RacGAP1 promotes its recruitment to IQGAP1 at the tips of invasive pseudopods, and RacGAP1 then locally suppresses the activity of the cytoskeletal regulator Rac and promotes the activity of RhoA in this subcellular region. This Rac to RhoA switch promotes the extension of pseudopodial processes and invasive migration into FN-containing matrices, in a RhoA-dependent manner. Thus, the localized endocytic trafficking of α5ß1 within the tips of invasive pseudopods elicits signals that promote the reorganization of the actin cytoskeleton, protrusion, and invasion into FN-rich ECM.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Ováricas
/
Proteínas de Unión al GTP rac
/
Proteína de Unión al GTP rhoA
/
Proteínas Activadoras de GTPasa
/
Proteínas Activadoras de ras GTPasa
/
Integrina alfa5beta1
/
Proteínas Adaptadoras Transductoras de Señales
/
Fibrosarcoma
/
Proteínas de la Membrana
Límite:
Female
/
Humans
Idioma:
En
Revista:
J Cell Biol
Año:
2013
Tipo del documento:
Article
Pais de publicación:
Estados Unidos