Mutual Regulation of PREX2 and PTEN

Phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchanger 2 (PREX2) is a guanine nucleotide exchange factor (GEF) for the GTPase RAC1, and we are interested in the role of PREX2 in cellular signaling and cancer. PREX2 expression is increased in many different tumor types, and it is also the most mutated GEF in cancer. In addition, PREX2 knockout mice have deficient glucose uptake and are insulin resistant, highlighting the importance of PREX2 in insulin signaling. Our lab identified PREX2 as a PTEN binding protein that inhibits PTEN phosphatase activity and we continue to investigate the importance of PTEN inhibition by PREX2 in cancer and in insulin signaling. Further, we are interested in how PREX2 function is actually regulated downstream of insulin and general growth factor stimulation. We are investigating various aspects of PREX2 regulation during growth factor signaling, including PREX2 post translational modifications, and also how these forms of regulation are potentially co-opted by cancer cells.