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D505 Richards
Bldg/6085 Email: ferguso2@mail.med.upenn.edu |
We are interested in the stereochemical details of molecular interactions in signal transduction pathways, in particular those emanating from the stimulation of cell surface receptors by growth factors. Recent work has led to the proposal of a novel mechanism for the growth factor activation of one of the receptors we study, the Epidermal Growth Factor (EGF) receptor. Using X-ray crystallography combined with a variety of biophysical and biochemical approaches, we are addressing the implications of this model on both the activation and inhibition of the EGF receptor. Developing, directions in the laboratory involve biophysical and structural studies of protein-protein interactions that control events in intracellular vesicle trafficking pathways and endocytosis, and in innate immune signaling. Selected
Publications: Li, S., K. Schmitz, P.D. Jeffrey, J. Wiltzius, P. Kussie, and K.M. Ferguson (2005) Structural basis for inhibition of the Epidermal Growth Factor Receptor by cetuximab. Cancer Cell 7:301-311. Dawson, J.P., M.B. Berger, C.-C. Lin, J. Schlessinger, M.A. Lemmon, and K.M. Ferguson (2005) Epidermal Growth Factor receptor dimerization and activation require ligand-induced conformational changes in the dimer interface. Mol. Cell. Biol 25:7734-7742. Bouyain S., P.A. Longo, S. Li, K.M. Ferguson, D.J. Leahy (2005) The extracellular region of ErbB4 adopts a tethered conformation in the absence of ligand. Proc. Natl. Acad. Sci. (USA) 102:15024-15029. Ferguson, K.M. (2004) Active and inactive conformations of the epidermal growth factor receptor. Biochem. Soc. Trans. 32:742-7455. Burgess, A.W., H.S. Cho, C. Eigenbrot, K.M. Ferguson, T.P.J. Garrett, D.J. Leahy, M.A. Lemmon, M.X. Sliwkowski, C.W. Ward, and S. Yokoyama (2003) An open-and-shut case? Recent insights into the activation of EGF/ErbB receptors. Molecular Cell 12:541-552. Ferguson, K.M., M.B. Berger, J.M. Mendrola, H.S. Cho, D.J. Leahy, and M.A. Lemmon (2003) EGF activates its receptor by removing interactions that auto-inhibit ectodomain dimerization. Molecular Cell 11:507-517. |
