References:
- Cho KJ, Park JH, Piggott AM, Salim AA, Gorfe A, Parton RG, Capon RJ, Lacey E, Hancock JF. (2012) Staurosporines disrupt phosphatidylserine trafficking and mislocalize Ras proteins. J Biol Chem. 287, 43573-43584.
- Sykes AM, Palstra N, Abankwa D, Hill JM, Skeldal S, Matusica D, Venkatraman P, Hancock JF, Coulson EJ. (2012) The effects of transmembrane sequence and dimerization on cleavage of the p75 neurotrophin receptor by γ-secretase. J Biol Chem. 287, 43810-43824.
- Hill MM, Daud NH, Aung CS, Loo D, Martin S, Murphy S, Black DM, Barry R, Simpson F, Liu L, Pilch PF, Hancock JF, Parat MO, Parton RG. (2012) Co-regulation of cell polarization and migration by caveolar proteins PTRF/cavin-1 and caveolin-1. PLoS One. 7: e43041.
- Collins B, Davis MJ, Hancock JF, Parton RG. (2012) Structure-based reassessment of the caveolin signaling model: do caveolae regulate signaling through caveolin-protein interactions? Dev Cell, 23, 11-20.
- Cho K-j, Kasai RS, Park J-H, Chigurupati S, Heidorn SJ, van der Hoeven D, Plowman SJ, Kusumi A, Marais R, Hancock JF. (2012) Raf inhibitors dysregulate the spatiotemporal dynamics of Ras proteins on the plasma membrane. Curr Biol. 22, 945-955.
- Lanosi J, Li Z, Hancock JF, Gorfe AA. (2012) Organization, dynamics and segregation of Ras nanoclusters in membrane domains. Proc Natl Acad Sci USA. 109, 8097-8102.
- Walser PJ, Ariotti N, Howes M, Ferguson C, Webb R, Schwudke D, Leneva N, Cho KJ, Cooper L, Rae J, Floetenmeyer M , Oorschot VM, Skoglund U, Simons K, Hancock JF, Parton RG. (2012) Constitutive formation of caveolae in a bacterium. Cell.150, 752-763.
- Zhou Y, Cho K-j, Plowman SJ, Hancock JF. (2012) Non-steroidal anti-inflammatory drugs alter the spatiotemporal organization of Ras proteins on the plasma membrane. J Biol Chem. 287, 16586-16595.
- Prior IA, Hancock JF. (2012) Ras trafficking, localization and compartmentalized signalling. Semin Cell Dev Biol. 23, 145-153.
- Cho K-j, Hill MH, Chigurupati S, Du G, Parton RG, Hancock JF. (2011) Therapeutic levels of the HMG-CoA reductase inhibitor lovastatin activate Ras signaling via phospholipase D2. Mol Cell Biol. 31, 1110-20.
- Abankwa D, Gorfe AA, Inder K, and Hancock JF. (2010) Membrane orientation and nanodomain localization generate Ras isoform diversity. Proc Natl Acad Sci USA. 107, 1130-1135.
- Ariotti N, Liang H, Xu Y, ZhangY, Yonekubo Y, Inder K, Du G, Parton RG, Hancock JF, and Plowman SJ. (2010) EGFR activation remodels the plasma membrane lipid environment to induce nanocluster formation. Mol Cell Biol 30, 3795-3804.
- Crouthamel M, Abankwa D, Zhang L, Dilizio C, Manning DR, Hancock JF and Wedegaertner PB. (2010). An N-terminal polybasic motif of Gq is required for signaling and influences membrane nanodomain distribution. Mol Pharmacol 78, 767-777.
- Howes MT, Kirkham M, Riches J, Cortese K, Walser PJ, Simpson F, Hill MM, Jones A, Lundmark R, Lindsay MR, Hernandez-Deviez DJ, Hadzic G, McCluskey A, Bashir R, Liu L, Pilch P, McMahon H, Robinson PJ, Hancock JF, Mayor S and Parton RG. (2010). Clathrin-independent carriers form a high capacity endocytic sorting system at the leading edge of migrating cells. J Cell Biol 190, 675-91.
- Kholodenko BN, Hancock JF and Kolch W. (2010). Signalling ballet in four dimensions. Nature Rev Mol Cell Biol 11, 414-426.
- Rotblat B, Belanis L, Hancock JF, Kloog Y and Plowman SJ. (2010). H-Ras nanocluster stability regulates the magnitude of MAPK signal output. PLoS One 5, e11991.
- Tian T, Plowman SJ, Parton RG, Kloog Y and Hancock JF. (2010). Mathematical modeling of K-Ras nanocluster formation on the plasma membrane. Biophys J 99, 534-543.
- Zhou Y, Hancock JF and Lichtenberger L. (2010). Nonsteroidal anti-inflammatory drug indomethacin induces phase heterogeneity in mixed lipid membranes: potential implication for its diverse biological actions. PLoS One 5, e8811.
- Zhou Y, Lichtenberger L and Hancock JF. (2010). The anti-inflammatory drug indomethacin alters nanoclustering in synthetic and cell plasma membranes. J Biol Chem 285, 35188-35195.
- Bastiani M, Liu L, Hill MH, Jedrychowski MP, Nixon SJ, Lo HP, Abankwa D, Luetterforst R, Fernandez-Rojo, Breen MR, Steven P, Gygi SP, Vinten J, Walser PJ, North KN, Hancock JF, Pilch PF and Parton RG (2009). MURC/Cavin-4 and cavin family members form tissue-specific caveolar complexes. J Cell Biol, 185, 1259-1273.
- Botelho RJ, Harrison RE, Stone JC, Hancock JF, Philips MR, Jongstra-Bilen J, Mason D, Plumb J, Gold MR, Grinstein S (2009). Localized diacylglycerol-dependent stimulation of Ras and Rap during phagocytosis. J Biol Chem, 284, 28522-28532.
- Inder K, Lau C, Loo D, Chaudhary N,Goodall A, Martin S, Jones A, Parton RG, Hill M and Hancock JF (2009). Nucleophosmin and nucleolin regulate K-Ras plasma membrane interactions and MAPK signal transduction. J Biol Chem, 284, 28410-28419.
- Ingelmo-Torres M, González-Moreno E, Kassan A, Hanzal-Bayer M, Tebar F, Herms A, Grewal T, Hancock JF, Enrich C, Bosch M, Gross S, Parton RG and Pol A (2009). Hydrophobic and basic domains target proteins to lipid droplets. Traffic, 10, 1785-1801.
- Kiskowski MA, Hancock JF, Kenworthy AK (2009). On the use of Ripley's K-function and its derivatives to analyze domain size. Biophys J, 97,1095-103.
- Prior IA, Hancock JF, Henis Y (2009). Ras acylation, compartmentalization and signaling nanoclusters. Mol Membr Biol, 26, 80-92.
- Puji A, Pike T, Widberg C, Payne E, Harding A, Hancock JF, Gabrielli B (2009). MAPK pathway activation delays G2/M progression by destabilizing CDC25B. J Biol Chem, 284, 33781-33788.
- Inder K, Harding A, Philips MR, Parton RG and Hancock JF. (2008) Activation of the MAPK module from different spatial locations generates distinct system outputs. Mol Biol Cell, 19, 4776-4784
- Shalom-Feuerstein R, Plowman SJ, Rotblat B, Ariotti N, Tian T, Hancock JF and Kloog Y. (2008) K-Ras nanoclustering is subverted by over-expression of the scaffold protein galectin-3. Cancer Res, 68, 6608-6616
- Harding A and Hancock JF. (2008) Using plasma membrane nanoclusters to build better circuits. Trends Cell Sci, 18, 364-371
- Plowman SJ, Ariotti N, Parton RG and Hancock JF. (2008) Electrostatic interactions positively regulate K-Ras nanocluster formation and function. Mol Cell Biol, 28, 4377-4385
- Abankwa D, Hanzal-Bayer M, Ariotti N, Plowman SJ, Gorfe AA, Parton RG, McCammon JA, and Hancock JF. (2008) A novel switch region regulates H-ras membrane orientation and signal output. EMBO J, 27, 727-735
- Belanis L, Plowman SJ, Rotblat B, Hancock JF and Kloog Y. (2008) Galectin-1 is a novel structural component and major regulator of H-ras nanoclusters. Mol Biol Cell, 19, 1404-1414
- Hill MH, Bastiani M, Luetterforst R, Kirkham M, Kirkham A, Nixon SJ, Walser P, Abankwa D, Oorschot VMJ, Martin S, Hancock JF and Parton RG. (2008) PTRF, a novel, conserved caveolar coat protein that regulates caveolae formation and function. Cell, 132, 113-124
- Tian T, Harding A, Inder K, Plowman SJ, Parton RG and Hancock JF. (2007) Plasma membrane nanoswitches generate high-fidelity Ras signal transduction. Nature Cell Biol, 9, 905-914
- Hancock JF. (2007) PA promoted to manager. Nature Cell Biol, 9, 615-617
- Abankwa D, Gorfe AA and Hancock JF. (2007) Ras nanoclusters: molecular structure and assembly. Semin Cell Dev Biol, 18, 599-607
- Nicolau Jr. DV, Hancock JF, Burrage K. (2007) Sources of Anomalous Diffusion on Cell Membranes: A Monte Carlo Study. Biophys J, 92, 1975-1987
- Hancock JF. (2006) Lipid rafts: contentious only from simplistic standpoints. Nature Rev Mol Cell Biol, 7, 456-462
John F. Hancock , M.B, B.Chir, Ph.D.
IBP Chair and Professor
UTHSC, Medical School, (713) 500-7547
John.F.Hancock@uth.tmc.edu
Education:
B.A.: University of Cambridge, 1978
M.B., B.Chir.: University of Cambridge, 1981
M.A.: University of Cambridge, 1982
Ph.D.: University of London, 1989
Sc.D.: University of Cambridge, 2013
Plasma Membrane Nanostructure and Signal Transduction
Our group studies mammalian intracellular signalling. We are especially interested in the function of Ras proteins. These small GTP binding proteins operate as molecular switches in signal transduction pathways and are present in a mutant, activated state in many human tumours. Understanding the basic biology of Ras has major implications for the development of novel anticancer therapeutics.
Specifically, we are investigating how the Ras membrane anchors cooperate with the G-domain and peptide sequences flanking the anchor to drive lateral segregation. Our work suggests new models are needed to explain how lipidated proteins interact with, and use, the plasma membrane to generate signalling platforms.
We remain interested in how confinement of signalling complexes onto a 2D surface in general and in plasma membrane nanodomains in particular regulates the kinetics and sensitivity of Raf/MEK/Erk signal output. Similarly, as we develop our spatial and proteomic maps of the plasma membrane, we can address how the composition and organization of the membrane alters in response to specific growth factors. The integration of complex spatial, kinetic, and biochemical data sets increasingly requires mathematical modelling to generate and test our novel hypotheses of nanodomain structure and function.
We also have a major interest in characterizing the K-ras ER to plasma membrane trafficking pathway and studying the biology of Ras prenyl binding proteins such as PDE delta.
- Research projects
- Molecular mapping of the proteins and lipids of plasma membrane nanodomains
- Electron microscopic visualisation and quantitative characterisation of surface nanodomains to build up a high-resolution 2D map of the nanodomains of the inner plasma membrane
- Investigation of the dynamic regulation of nanodomain localisation of Ras and Ras-interacting proteins in response to physiological stimuli
- Characterisation of the mechanism(s) whereby K-ras is transported to the plasma membrane
- Mathematical modelling of Ras signal transduction
- Monte Carlo modelling of plasma membrane nanodomain dynamics
