Protein tyrosine phosphatase-PEST and ß8 integrin regulate spatiotemporal patterns of RhoGDI1 activation in migrating cells.
Mol Cell Biol
; 35(8): 1401-13, 2015 Apr.
Article
em En
| MEDLINE
| ID: mdl-25666508
ABSTRACT
Directional cell motility is essential for normal development and physiology, although how motile cells spatiotemporally activate signaling events remains largely unknown. Here, we have characterized an adhesion and signaling unit comprised of protein tyrosine phosphatase (PTP)-PEST and the extracellular matrix (ECM) adhesion receptor ß8 integrin that plays essential roles in directional cell motility. ß8 integrin and PTP-PEST form protein complexes at the leading edge of migrating cells and balance patterns of Rac1 and Cdc42 signaling by controlling the subcellular localization and phosphorylation status of Rho GDP dissociation inhibitor 1 (RhoGDI1). Translocation of Src-phosphorylated RhoGDI1 to the cell's leading edge promotes local activation of Rac1 and Cdc42, whereas dephosphorylation of RhoGDI1 by integrin-bound PTP-PEST promotes RhoGDI1 release from the membrane and sequestration of inactive Rac1/Cdc42 in the cytoplasm. Collectively, these data reveal a finely tuned regulatory mechanism for controlling signaling events at the leading edge of directionally migrating cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Movimento Celular
/
Cadeias beta de Integrinas
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Proteína Tirosina Fosfatase não Receptora Tipo 12
/
Inibidor alfa de Dissociação do Nucleotídeo Guanina rho
Limite:
Animals
Idioma:
En
Revista:
Mol Cell Biol
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Estados Unidos