This proposal is designed to study the role of focal adhesion kinase (FAK) in cell migration that is stimulated by various factors known to activate FAK, including integrin engagement to the extracellular matrix as well as treatment with growth factors. A novel approach has been designed to allow a temporal regulation of FAK in order to separate its role in cell spreading from that of migration. FRNK (FAK-related nonkinase) is a C-terminal piece of FAK that is autonomously expressed in some cells and functions as a dominant inhibitor of FAK function. A fusion has been constructed between FRNK and the hormone-binding domain of the estrogen receptor that results in a protein that is inhibitory only in the presence of hormone. Stable cell lines will be constructed that express different levels of FRNK-ER protein. These cells will be used to characterize FRNK-ER. In addition, this system will allow us to study the role of FAK in migration in response to different stimuli using two different models of cell migration.
| Kleman-Leyer, Karen M; Klink, Tony A; Kopp, Andrew L et al. (2009) Characterization and optimization of a red-shifted fluorescence polarization ADP detection assay. Assay Drug Dev Technol 7:56-67 |
| Liu, Yunhao; Loijens, Joost C; Martin, Karen H et al. (2002) The association of ASAP1, an ADP ribosylation factor-GTPase activating protein, with focal adhesion kinase contributes to the process of focal adhesion assembly. Mol Biol Cell 13:2147-56 |
| Martin, Karen H; Boerner, Scott A; Parsons, J Thomas (2002) Regulation of focal adhesion targeting and inhibitory functions of the FAK related protein FRNK using a novel estrogen receptor ""switch"". Cell Motil Cytoskeleton 51:76-88 |
