Lewis CantleyDepartment of Systems Biology
Chief, Division of Signal Transduction, BIDMC
Center for Life Sciences, Room 412
3 Blackfan Circle, Boston, MA 02115
We are interested in the biochemical basis for growth, survival and transformation of mammalian cells. We have developed a peptide library technique that allows us to determine the structural basis for specificity in protein/protein interactions that are involved in signal transduction cascades. This information is incorporated into a computer program that predicts likely signaling partners from scans of protein sequences of whole genomes. To evaluate the role of signaling proteins at the whole animal level, we delete the gene encoding the protein of interest in mice and characterize the effect on growth, development, metabolism and tumor formation. In particular, we are interested in pathways that utilize phosphorylation of inositol lipids as a mechanism for assembling signaling complexes at specific locations in membranes.
Christofk, H.R., Vander Heiden, M.G., Wu, N., Asara, J.M., and Cantley, L.C. (2008) Pyruvate kinase M2 is a phosphotyrosine-binding protein. Nature 452(7184): 181-6.
Christofk, H.R., Vander Heiden, M.G., Harris, M.H., Ramanathan, A., Gerszten, R.E., Wei, R., Fleming, M.D., Schreiber, S.L., and Cantley, L.C. (2008) The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature 452(7184): 230-3.
Engelman, J.A., Luo, J., and Cantley, L.C. (2006) The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nature Rev. Genet. 7(8): 606-19.
Shaw, R.J., Lamia, K.A., Vasquez, D., Koo, S.H., Bardeesy, N., Depinho, R.A., Montminy, M., and Cantley, L.C. (2005) The kinase LKB1 mediates glucose homeostasis in Liver and therapeutic effects of Metformin. Science 310(5754):1642-6.
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