Fox Chase Cancer Center
Graduate Group: Cell and Molecular Biology - Cell Biology and Physiology
Thesis Topic: Regulated protein sorting in the endosomal system
The Rho family GTPases Cdc42 and Rac are essential for Ras-mediated transformation of cultured cells and for Ras-induced tumor formation in mice. They contribute to tumorigenesis and metastasis through the activation of a diverse array of downstream effector proteins. One important effector protein of these small GTPases is p21-activated kinase 1 (Pak1) whic acts to regulate the actin cytoskeleton, resulting in increased cell motility and a metastatic phenotype. In addition, a substantial body of evidence has implicated phosphoinositides, specifically phosphatidylinositol-4,5-biphosphate (PIP2), as important regulators of signaling by Rho family GTPases. Using a combination of biochemical and cell-based assays, Dr. Strochlic tested the hypothesis that phosphoinositides and Rac/Cdc42 function cooperatively to activate Pak1 both in vitro and in vivo.