References:
- 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
Plasma Membrane Microstructure 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 microdomains 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 organisation 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 microdomain structure and function.
We also have a major interest in characterising 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 microdomains
• Electron microscopic visualisation and quantitative characterisation of surface microdomains to build up a high-resolution 2D map of the microdomains of the inner plasma membrane
• Investigation of the dynamic regulation of microdomain 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 microdomain dynamics
