Regulators and Effectors of Small GTPases: Ras Family

The Ras superfamily (>150 human members) encompasses Ras GTPases involved in cell proliferation, Rho GTPases involved in regulating the cytoskeleton, Rab GTPases involved in membrane targeting/fusion and a group of GTPases including Sar1, Arf, Arl and dynamin involved in vesicle budding/fission. These GTPases act as molecular switches and their activities are controlled by a large number of regulatory molecules that affect either GTP loading (guanine nucleotide exchange factors or GEFs) or GTP hydrolysis (GTPase activating proteins or GAPs). In their active state, they interact with a continually increasing, functionally complex array of downstream effectors. Since the last Methods in Enzymology volume on this topic in 2000, the study of Ras Family GTPases has witnessed a plethora of new directions and trends. With regards to the founding member of the Ras superfamily, the study of Ras in oncogenesis has seen the development and application of more advanced model cell culture and animal systems. The discovery of mutationally activated B-Raf in human cancers has injected renewed interest in this classical effector pathway of Ras.

Real-time in vitro measurement of Intrinsic and Ras GAP-mediated GTP hydrolysis; Schwann cell preparation from single mouse embryos: Analyses of neurofibromin function in Schwann cells; Regulation of the nucleotide state of oncogenic Ras proteins by nucleoside diphosphate kinase; Measurements of TSC2 GAP activity toward Rheb; Characterization of AND-34 function and signalling; Studying the spatial and temporal regulation of Ras GTPase-activating proteins; Activation of Ras Proteins by Ras Guanine Nucleotide Releasing Protein Family Members; Ras and Rap1 Activation of PLC? lipase activity; Specificity and expression of RalGPS as RalGEFs; Biochemical and biological analyses of Rgr RalGEF oncogene; Analysis of Ras Activation in Living Cells with GFP-RBD; Genetic and pharmacologic analyses of the role of Icmt in Ras membrane association and function; Characterization of the activation of the Rap specific exchange factor epac by cyclic nucleotides; Biochemistry of the Rap-specific guanine nucleotide exchange factors PDZ-GEF1 and 2; Characterization of interactions between Ras family GTPases and their effectors; Genetic and pharmacologic dissection of Ras effector utilization in oncogenesis; Sequencing analysis of BRAF mutations in human cancers; KSR regulation of the Raf-MEK-ERK cascade; Ras-sensitive IMP modulation of the Raf/MEK/ERK cascade through KSR1; Raf Kinase Inhibitor Protein (RKIP) regulation of Raf and MAPK signalling; Harnessing RNAi for Analyses of Ras Signaling and Transformation; The Rac Activator Tiam1and Ras induced Oncogenesis; Phospholipase Ce CƒÕ guanine nucleotide exchange factor activity and activation of Rap1; Nore1 and RASSF1 regulation of cell proliferation and of the MST1/2 kinases; RASSF family proteins and Ras transformation; Ras and the Rain/RasBP1 effector; The RIN family of Ras effectors; RAP1 regulation of RIAM and cell adhesion; Regulation of cell-cell adhesion by Rap1; Effects of Ras signaling on gene expression analyzed by customized microrays; Protein-fragment complementation assays (PCA) in small GTPase research and drug discovery; Ras Up-regulation of Cycloxygenase-2; Regulation of the expression of tropomyosins and actin cytoskeleton by ras-transformation; Regulation of Par-4 by Oncogenic Ras; Using Drosophila and yeast genetics to investigate a role for the RhebGTPase in cell growth; Biochemistry and Biology of ARHI (DIRAS3), An Imprinted Tumor Suppressor Gene Whose Expression Is Lost In Ovarian and Breast Cancer; Gem protein signaling and regulation; Analysis of Rem/RGK Signaling and Biological Activity; Analysis of Rit Signaling and Biological Activity; Characterization of RERG: An estrogen-regulated tumor suppressor gene; Inhibition of transcription factor NF-?B activation by ?B-Ras; Analysis of Rhes activation state and effector function ; Rheb activation of mTOR and S6K1 signaling; Use of Retrovirus Expression of Interfering RNA to Determine the Contribution of Activated K-Ras and Ras Effector Expression to Human Tumor Cell Growth; Using inhibitors of prenylation to block localization and transforming activity; Sorafenib (BAY 43-9006), a dual action inhibitor that targets RAF/MEK/ERK pathway in tumor cells and tyrosine kinases VEGFR/PDGFR in tumor vasculature; Yeast screens for inhibitors of Ras-Raf interaction and characterization of MCP inhibitors of Ras-Raf interaction; A tagging-via-substrate technology for genome-wide detection and identification of farnesylated proteins; A genetically defined normal human somatic cell system to study Ras oncogenesis in vivo and in vitro; Analyses of Ras transformation of human thyroid epithelial cells; Use of Ras-transformed human ovarian surface epithelial cells as a model for studying ovarian cancer; Physiological analysis of oncogenesic Kras; Use of conditionally active Ras Fusion Proteins to study Epidermal Growth, Differentiation and Neoplasia; Pancreatic duct epithelial cell isolation and cultivation in two dimensional and three dimensional culture systems; Analyses of RAS regulation of eye development in Drosophila melanogaster; Ras superfamily and interacting proteins database

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