ASAP3 Is a Focal Adhesion-associated Arf GAP That Functions in Cell Migration and Invasion
| Autor: | Paul A. Randazzo, Hiroki Inoue, Armand de Gramont, Yvona Ward, Zhongzhen Nie, Sanita Bharti, Vi Luan Ha, Fanny Campa, William C. Vass |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Phosphatidylinositol 4
5-Diphosphate Stress fiber ADP ribosylation factor Podosome Biology Biochemistry Focal adhesion Mice Molecular Basis of Cell and Developmental Biology Cell Movement Cell Line Tumor Neoplasms Animals Humans Neoplasm Invasiveness Molecular Biology Actin Adaptor Proteins Signal Transducing Focal Adhesions Sequence Homology Amino Acid ADP-Ribosylation Factors GTPase-Activating Proteins Blood Proteins Cell Biology Phosphoproteins Neoplasm Proteins Protein Structure Tertiary Cell biology Pleckstrin homology domain ADP-Ribosylation Factor 6 Invadopodia Cancer cell NIH 3T3 Cells Cancer research ADP-Ribosylation Factor 1 Female |
| Zdroj: | Journal of Biological Chemistry. 283:14915-14926 |
| ISSN: | 0021-9258 |
| Popis: | ASAP3, an Arf GTPase-activating protein previously called DDEFL1 and ACAP4, has been implicated in the pathogenesis of hepatocellular carcinoma. We have examined in vitro and in vivo functions of ASAP3 and compared it to the related Arf GAP ASAP1 that has also been implicated in oncogenesis. ASAP3 was biochemically similar to ASAP1: the pleckstrin homology domain affected function of the catalytic domain by more than 100-fold; catalysis was stimulated by phosphatidylinositol 4,5-bisphosphate; and Arf1, Arf5, and Arf6 were used as substrates in vitro. Like ASAP1, ASAP3 associated with focal adhesions and circular dorsal ruffles. Different than ASAP1, ASAP3 did not localize to invadopodia or podosomes. Cells, derived from a mammary carcinoma and from a glioblastoma, with reduced ASAP3 expression had fewer actin stress fiber, reduced levels of phosphomyosin, and migrated more slowly than control cells. Reducing ASAP3 expression also slowed invasion of mammary carcinoma cells. In contrast, reduction of ASAP1 expression had no effect on migration or invasion. We propose that ASAP3 functions nonredundantly with ASAP1 to control cell movement and may have a role in cancer cell invasion. In comparing ASAP1 and ASAP3, we also found that invadopodia are dispensable for the invasive behavior of cells derived from a mammary carcinoma. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|