Ras Conformational Ensembles, Allostery, and Signaling

The phosphoinositide 3-kinase pathway

Cantley, L. C. (2002) · Science · doi:10.1126/science.296.5573.1655 · Cited by 5,621

ras GENES

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The GTPase superfamily: conserved structure and molecular mechanism

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Targeting RAS signalling pathways in cancer therapy

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The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism

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The Energy Landscapes and Motions of Proteins

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Targeting the phosphoinositide 3-kinase pathway in cancer

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K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions

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Small GTP-Binding Proteins

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COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer

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A Comprehensive Survey of Ras Mutations in Cancer

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The role of dynamic conformational ensembles in biomolecular recognition

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Drugging the undruggable RAS: Mission Possible?

Cox, A. D., Fesik, S. W., Kimmelman, A. C., Luo, J., & Der, C. J. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4389 · Cited by 1,997

Mammalian Ras interacts directly with the serine/threonine kinase raf

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GEFs and GAPs: Critical Elements in the Control of Small G Proteins

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RAS oncogenes: the first 30 years

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The Guanine Nucleotide-Binding Switch in Three Dimensions

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RAS oncogenes: weaving a tumorigenic web

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Model Systems, Lipid Rafts, and Cell Membranes

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Regulation of Phosphoinositide-Specific Phospholipase C

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Hyperactive Ras in developmental disorders and cancer

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The Ras-RasGAP Complex: Structural Basis for GTPase Activation and Its Loss in Oncogenic Ras Mutants

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Ras oncogenes: split personalities

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Meaningful relationships: the regulation of the Ras/Raf/MEK/ERK pathway by protein interactions

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The ensemble nature of allostery

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Regulation of Small GTPases by GEFs, GAPs, and GDIs

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A Cytoplasmic Protein Stimulates Normal N- ras p21 GTPase, But Does Not Affect Oncogenic Mutants

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Structural Determinants of Phosphoinositide 3-Kinase Inhibition by Wortmannin, LY294002, Quercetin, Myricetin, and Staurosporine

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Insights into Protein–Protein Binding by Binding Free Energy Calculation and Free Energy Decomposition for the Ras–Raf and Ras–RalGDS Complexes

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Targeting RAS–ERK signalling in cancer: promises and challenges

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Increasing complexity of Ras signaling

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Refined crystal structure of the triphosphate conformation of H‐ras p21 at 1.35 A resolution: implications for the mechanism of GTP hydrolysis.

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Molecular Switch for Signal Transduction: Structural Differences Between Active and Inactive Forms of Protooncogenic ras Proteins

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A polybasic domain or palmitoylation is required in addition to the CAAX motif to localize p21ras to the plasma membrane

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Human RAS Superfamily Proteins and Related GTPases

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Normal and oncogenic p21ras proteins bind to the amino-terminal regulatory domain of c-Raf-1

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Ras proteins: different signals from different locations

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Targeting RAF kinases for cancer therapy: BRAF-mutated melanoma and beyond

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Ras superfamily GEFs and GAPs: validated and tractable targets for cancer therapy?

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Blocking Oncogenic Ras Signaling for Cancer Therapy

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The structural basis of the activation of Ras by Sos

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Human Sos1: a Guanine Nucleotide Exchange Factor for Ras that Binds to GRB2

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Dragging ras back in the ring

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Biochemical and Structural Analysis of Common Cancer-Associated KRAS Mutations

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Understanding Ras: ‘it ain’t over ’til it’s over’

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Allostery in Disease and in Drug Discovery

Nussinov, R., & Tsai, C. (2013) · Cell · doi:10.1016/j.cell.2013.03.034 · Cited by 769

RAS Interaction with PI3K: More Than Just Another Effector Pathway

Castellano, E., & Downward, J. (2011) · Genes & Cancer · doi:10.1177/1947601911408079 · Cited by 762

Endomembrane Trafficking of Ras

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The RAS/RAF/MEK/ERK and the PI3K/AKT signalling pathways: role in cancer pathogenesis and implications for therapeutic approaches

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Direct visualization of Ras proteins in spatially distinct cell surface microdomains

Prior, I. A., Muncke, C., Parton, R. G., & Hancock, J. F. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200209091 · Cited by 743

Ras history: The saga continues

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KRAS: feeding pancreatic cancer proliferation

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Multiple ras functions can contribute to mammalian cell transformation

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Folding funnels, binding funnels, and protein function

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The 2.2 Å crystal structure of the Ras-binding domain of the serine/threonine kinase c-Raf1 in complex with RaplA and a GTP analogue

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Accessing protein conformational ensembles using room-temperature X-ray crystallography

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Small-molecule ligands bind to a distinct pocket in Ras and inhibit SOS-mediated nucleotide exchange activity

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Crystal Structure and Functional Analysis of Ras Binding to Its Effector Phosphoinositide 3-Kinase γ

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Binding of Ras to Phosphoinositide 3-Kinase p110α Is Required for Ras- Driven Tumorigenesis in Mice

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Small molecule inhibition of the KRAS–PDEδ interaction impairs oncogenic KRAS signalling

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Folding and binding cascades: Dynamic landscapes and population shifts

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Ras signalling on the endoplasmic reticulum and the Golgi

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The p21 ras C-terminus is required for transformation and membrane association

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Regulating the regulator: post-translational modification of RAS

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An Unidentified Virus which causes the Rapid Production of Tumours in Mice

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The Structure of a Human p110α/p85α Complex Elucidates the Effects of Oncogenic PI3Kα Mutations

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Three-Dimensional Structure of an Oncogene Protein: Catalytic Domain of Human c-H- ras P21

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Oncogenic KRAS signalling in pancreatic cancer

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The challenge of lipid rafts

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G-protein signaling: back to the future

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Guanosine Triphosphatase Activating Protein (GAP) Interacts with the p21 ras Effector Binding Domain

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Discovery of Small Molecules that Bind to K‐Ras and Inhibit Sos‐Mediated Activation

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Structural Evidence for Feedback Activation by Ras·GTP of the Ras-Specific Nucleotide Exchange Factor SOS

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Structure-Function Relationships of the G Domain, a Canonical Switch Motif

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H-ras, K-ras, and inner plasma membrane raft proteins operate in nanoclusters with differential dependence on the actin cytoskeleton

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Ras effectors

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Dominant-negative caveolin inhibits H-Ras function by disrupting cholesterol-rich plasma membrane domains

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The role of lipid rafts in T cell antigen receptor (TCR) signalling

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Helical domain and kinase domain mutations in p110α of phosphatidylinositol 3-kinase induce gain of function by different mechanisms

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Localization of Epidermal Growth Factor-stimulated Ras/Raf-1 Interaction to Caveolae Membrane

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p110δ, a novel phosphoinositide 3-kinase in leukocytes

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Multiple diverse ligands binding at a single protein site: A matter of pre‐existing populations

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GTPase-activating proteins: Helping hands to complement an active site

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Signaling Interplay in Ras Superfamily Function

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A Unified View of “How Allostery Works”

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Digital signaling and hysteresis characterize Ras activation in lymphoid cells.

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Three-dimensional structures of H-ras p21 mutants: Molecular basis for their inability to function as signal switch molecules

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Tethering: Fragment-Based Drug Discovery

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Cholesterol Depletion of Caveolae Causes Hyperactivation of Extracellular Signal-related Kinase (ERK)

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RAF protein-serine/threonine kinases: Structure and regulation

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Stimulation of Membrane Ruffling and MAP Kinase Activation by Distinct Effectors of RAS

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Single-molecule imaging analysis of Ras activation in living cells

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Confirmation of the arginine-finger hypothesis for the GAP-stimulated GTP-hydrolysis reaction of Ras

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Folding and binding cascades: Shifts in energy landscapes

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Phospholipase Cϵ: a novel Ras effector

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Targeting RAS Membrane Association: Back to the Future for Anti-RAS Drug Discovery?

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Quantitative Analysis of the Complex between p21 and the Ras-binding Domain of the Human Raf-1 Protein Kinase

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Genetic analysis of Ras signalling pathways in cell proliferation, migration and survival

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Oncogenic Ras Activation of Raf/Mitogen-Activated Protein Kinase-Independent Pathways Is Sufficient To Cause Tumorigenic Transformation

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Regulation of the MST1 kinase by autophosphorylation, by the growth inhibitory proteins, RASSF1 and NORE1, and by Ras

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Thematic review series: Lipid Posttranslational Modifications CAAX modification and membrane targeting of Ras

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GEFs: structural basis for their activation of small GTP-binding proteins

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Therapeutic Strategies for Targeting Ras Proteins

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