Adenomatous Polyposis Coli and Asef Function Downstream of Hepatocyte Growth Factor and Phosphatidylinositol 3-Kinase*
AUTOR(ES)
Kawasaki, Yoshihiro
FONTE
American Society for Biochemistry and Molecular Biology
RESUMO
Mutations of the tumor suppressor adenomatous polyposis coli (APC) are responsible for sporadic and familial colorectal tumors. APC negatively regulates Wnt signaling by inducing β-catenin degradation. It has also been shown that APC plays a role in the organization of cytoskeletal networks. APC interacts with Asef and Asef2, Rac1- and Cdc42-specific guanine nucleotide exchange factors (GEFs), and stimulates their GEF activity; thereby regulating cell morphology, adhesion, and migration. Truncated mutant APCs present in colorectal tumor cells activate Asef and Asef2 constitutively and contribute to their aberrant migratory properties. We show here that hepatocyte growth factor (HGF), as well as basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF), induce the accumulation and colocalization of APC and Asef in membrane ruffles and lamellipodia of epithelial cells. Both APC and Asef were found to be required for HGF-induced cell migration. Furthermore, we show that the effects of HGF, bFGF, and EGF on APC and Asef are mediated by the activation of phosphatidylinositol 3-kinase (PI3-kinase) and require the PH domain of Asef. These results suggest that Asef and APC function downstream of HGF and PI3-kinase, and play critical roles in growth factor-mediated regulation of cell morphology and migration.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2755965Documentos Relacionados
- Anti-apoptotic signaling by hepatocyte growth factor/Met via the phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase pathways
- Association and regulation of casein kinase 2 activity by adenomatous polyposis coli protein
- A novel recognition motif for phosphatidylinositol 3-kinase binding mediates its association with the hepatocyte growth factor/scatter factor receptor.
- A CA repeat 30–70 Kb downstream from the adenomatous polyposis coli (APC) gene
- A CA repeat 30–70 KB downstream from the adenomatous polyposis coli (APC) gene