Shp-2 tyrosine phosphatase is required for hepatocyte growth factor-induced activation of sphingosine kinase and migration in embryonic fibroblasts.
Cell Signal
; 18(11): 2049-55, 2006 Nov.
Article
em En
| MEDLINE
| ID: mdl-16765027
ABSTRACT
Shp-2, a ubiquitously expressed protein tyrosine phosphatase containing two Src homology 2 domains, plays an important role in integrating signaling from the cell surface receptors to intracellular signaling mechanisms. Previous studies have demonstrated that the Shp-2 is involved in hepatocyte growth factor (HGF)-induced cell scattering. Here we report that Shp-2 is required for the HGF-induced activation of sphingosine kinase-1 (SPK1), a highly conserved lipid kinase that plays an important role in cell migration. Loss-of-function mutation of Shp-2 did not affect the expression of SPK1, but resulted in its inactivation and the blockage of HGF-induced migration in embryonic fibroblasts. Reintroduction of functional wild type (WT) Shp-2 into the mutant cells partially restored SPK1 activation, and overexpression of SPK1 in these mutant cells enhanced HGF-induced cell migration. Inhibition of expression or activity of SPK1 in WT cells markedly decreased intracellular S1P levels and HGF-induced cell migration. Furthermore, we found that Shp-2 co-immunoprecipitated with SPK1 and c-Met in embryonic fibroblasts. These studies suggest that Shp-2 is an SPK1-interacting protein and that it plays an indispensable role in HGF-induced SPK1 activation.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Movimento Celular
/
Proteínas Tirosina Fosfatases
/
Fator de Crescimento de Hepatócito
/
Fosfotransferases (Aceptor do Grupo Álcool)
/
Peptídeos e Proteínas de Sinalização Intracelular
/
Fibroblastos
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article