Regulation of Rho-GTPase pathways by the adaptor protein, Dok-4

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Epithelial cells are lining the walls of important structures in body organs such as lungs, intestines and the kidney. Our laboratory studies how the epithelial cells work, specifically focusing on the kidney. In response to injury, growth factors produced naturally in the kidney help the damaged epithelial cells to regenerate, in part by promoting the capacity of cells to divide and increase in numbers to replace dead cells. However, these newly regenerated cells need to regain sophisticated structure by the process called differentiation in order to restore their normal functions. We propose that a molecule called Dok-4 will help balance various regulators of the cell structure thereby contributing to the differentiation of epithelial cells. In this study, we will examine how Dok-4 is turned on at a certain stage of epithelial cell recovery and switches off one regulatory protein while switches on another regulatory protein of an opposing function. We expect that Dok-4 will act as a critical molecular switch which will direct the cells toward full recovery of function after an injury.