University of Virginia Health System

Protein Phosphatases in Cell Signaling and the Cell Cycle

The dominant mechanism for cell signaling is protein phosphorylation. Thousands of cellular proteins undergo phosphorylation to control their activity, but most of the time they are kept in their dephosphorylated state by the action of protein phosphatases. Phosphatases specific for P-Ser and P-Thr (PP1, PP2A, PP4, PP6) are ancient enzymes, conserved between yeast and humans, and genetics shows they are essential for mitosis and for stages of cell cycle growth and cell proliferation. Toxins from cyanobacteria, dinoflagelates and insects target the active sites of these phosphatases. Cells must strictly regulate the activity of these abundant phosphatases to respond to changes in their environment. This is done through sending signals to phosphatase regulatory and catalytic subunits, plus specific inhibitor proteins. Current research in our group investigates the molecular basis for recognition among these proteins, and tests how phosphatases operate in living cells in response to changing conditions. We are determining the structure and biochemical properties of purified recombinant proteins. We use genomics to find novel related proteins and genetic screens to find binding partners. Fluorescent fusion proteins and phosphorylation-specific antibodies are employed with microscopic digital imaging to study where, when and how proteins become activated and localized within cells. The results are expected to give a better understanding of cell division, cytoskeletal reorganization, metabolic regulation and how defects in these processes lead to human diseases.
[see website of Center for more detailed description of research projects] http://www.healthsystem.virginia.edu/internet/cellsignaling/dbrautiganresearchinterest.cfm

Other Websites for this mentor:
http://www.healthsystem.virginia.edu/internet/cellsignaling/