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Targeting of the protein interaction site between FAK and IGF-1R |
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| Authors: | Donghang Zheng Elena Kurenova Vita Golubovskaya David Ostrov William G. Cance |
| Affiliation: | a Department of Surgery, University of Florida, Gainesville, FL, USA b Molecular Genetics and Microbiology, University of Florida, Gainesville, FL, USA c UF Shands Cancer Center, University of Florida, Gainesville, FL, USA d Department of Pathology and Laboratory Medicine, University of Florida, Gainesville, FL, USA e Department of Surgery, Roswell Park Cancer Institute, Buffalo, NY, USA |
| Abstract: | The interaction of focal adhesion kinase (FAK) and insulin-like growth factor-1 receptor (IGF-1R) plays an important role in cancer cell survival. Targeting this interaction with small molecule drugs could be a novel strategy in cancer therapy. By a series of pull-down assays using GST-tagged FAK fragments and His-tagged IGF-1R intracellular fragments, we showed that the FAK-NT2 (a.a. 127-243) domain directly interacts with the N-terminal part of the IGF-1R intracellular domain. Overexpressed FAK-NT2 domain was also shown to co-localize with IGF-1R in pancreatic cells. Computational modeling was used to predict the binding configuration of these two domains and to screen for small molecules binding to the interaction site. This strategy successfully identified a lead compound that disrupts FAK/IGF-1R interaction. |
| Keywords: | FAK Protein-protein interaction IGF-1R Small molecule inhibitor |
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