References:
- Nicolau Jr., D.V., Burrage, K., Parton, R.G., and Hancock, J.F. (2006). Identifying optimal lipid raft characteristics required to promote nano-scale protein-protein interactions on the plasma membrane. Molecular Cell Biology 26: 313-323.
- Harding, A., Tian, T., Westbury, E., Frische, E., and Hancock, J.F. (2005). Subcellular localization determines MAP Kinase signal output. Current Biology 15: 869-873.
- Plowman, S., Muncke, C., Parton, R.G., and Hancock, J.F. (2005). H-ras, K-ras and inner plasma membrane raft proteins operate in nanoclusters with differential dependence on the actin cytoskeleton. Proceedings of the National Academy of Sciences USA 102: 15500-15505.
- Roy, S., Plowman, S., Rotblat, B., Prior, I.A., Muncke, C., Parton, R.G., Henis, Y.I., Kloog, Y., and Hancock, J.F. (2005). Individual palmitoyl residues serve distinct roles in H-Ras trafficking, microlocalization and signaling. Molecular Cell Biology 25: 6722-6733.
- Hancock, J.F., and Parton, R.G. (2005). Ras plasma membrane signalling platforms. Biochemical Journal 389: 1-11.
- Hancock, J.F. (2003). Ras proteins: Different signals from different locations. Nature Reviews Molecular Cell Biology 4: 373-385.
- Prior, I.A., Muncke, C., Parton, R.G., and Hancock, J.F. (2003). Direct visualisation of Ras proteins in spatially distinct cell surface microdomains. Journal of Cell Biology 160: 165-170.
John F. Hancock , M.B, B.Chir, Ph.D.
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
