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Specific SHP-2 partitioning in raft domains triggers integrin-mediated signaling via Rho activation

AutorLacalle, Rosa Ana; Mira, Emilia; Gómez-Moutón, Concepción; Jiménez Baranda, Sonia; Martínez-Alonso, Carlos; Mañes, Santos
Fecha de publicaciónabr-2002
EditorRockefeller University Press
CitaciónThe Journal of Cell Biology, volume 157, number 2, april 15, 2002, pp. 277–289
ResumenCell signaling does not occur randomly over the cell surface, but is integrated within cholesterol-enriched membrane domains, termed rafts. By targeting SHP-2 to raft domains or to a non-raft plasma membrane fraction, we studied the functional role of rafts in signaling. Serumdepleted, nonattached cells expressing the raft SHP-2 form, but not non-raft SHP-2, display signaling events resembling those observed after fibronectin attachment, such as 1 integrin clustering, 397 Y-FAK phosphorylation, and ERK activation, and also increases Rho-GTP levels. Expression of C the dominant negative N19Rho abrogates raft-SHP-2–induced signaling, suggesting that Rho activation is a downstream event in SHP-2 signaling. Expression of a catalytic inactive SHP-2 mutant abrogates the adhesion-induced feedback inhibition of Rho activity, suggesting that SHP-2 contributes to adhesion-induced suppression of Rho activity. Because raft recruitment of SHP-2 occurs physiologically after cell attachment, these results provide a mechanism by which SHP-2 may influence cell adhesion and migration by spatially regulating Rho activity.
DescripciónCopyright © by The Rockefeller University Press
URIhttp://hdl.handle.net/10261/3387
DOI10.1083/jcb.200109031
ISSN0021-9525
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