Le Breton Lab Research
Assembly and Regulation of the Cytoskeleton
Blood Platelets have been implicated in the genesis of certain forms of cardiovascular disease
(e.g., heart attack and stroke) in addition to being involved in the control of blood loss upon vascular damage.
Based on this consideration, a more complete understanding of the fundamental mechanisms involved in platelet
activation and inhibition would facilitate the development of pharmacological agents useful in the prevention
and management of thromboembolic disorders. To this end, our research program employs a wide range of chemical,
biochemical and pharmacological techniques to study blood platelet signal transduction pathways. Specifically,
novel chemical and immunological tools are developed and in turn utilized as pharmacological probes to: 1.
elucidate the sequence of events leading to platelet activation; 2. identify and characterize specific proteins
involved in the signal transduction process; and 3. investigate selective pharmacological intervention that
regulate the state of human blood platelet reactivity.
- Djellas, Y., Antonakis, K. and Le Breton, G.C.: A novel signaling mechanism between seven-transmembrane receptors: Evidence for a redistribution of G-proteins. Proc. Natl. Acad. Sci, 95:18944-18948, 1998.
- Djellas, Y., Manganello, J., Antonakis, K. and Le Breton, G.C.: Identification of G13 as one of the G-proteins which couple to human platelet TXA2 receptors. J. Biol. Chem. 274:14325-330, 1999.
- Manganello, J., Djellas, Y., Antonakis, K. and Le Breton, G.C.: cAMP-dependent phosphorylation of TXA2 receptor-associated G 13 J. Biol. Chem. 274: 28003-28010, 1999.
- Blackman, S. Borg, C., Yeomans, D., and Le Breton, G.C. Assessment of cellular localization of the thromboxane A2 receptor by immunocytochemistry. In: Methods in Molecular Medicine. Humana Press, Totowa, N.J. vol. 120:145-171, 1999.
- Halmos, T., Turek, J.W., Le Breton, G.C. and Antonakis, K.: Synthesis and biological characterization of a novel biotinylated photoaffinity probe for platelet TXA2 receptors, Bioorgan. & Med. Chem. Lett. 9: 2963-2968, 1999.
- Djellas, Y., Antonakis, K. and Le Breton, G.C.: Shifts in the affinity of one seven-transmembrane receptor by activation of a separate seven-transmembrane receptor. Biochem. Pharmacol. 59: 1521-1529, 2000.
- Muja, N., Blackman, S., Le Breton, G.C., and DeVries, G.H.:Identification and functional characterization of thromboxane receptors in Schwann cells. Journal of Neurochemistry: 78, 446-456, 2001.
- Turek, J.W., Y., Antonakis, K. and Le Breton, G.C.: Mapping of a ligand-binding site for the human thromboxane A2 receptor protein. J. Biol. Chem. 277: 16791-16797, 2002.
- Manganello,J.M., Huang,J.-S., Kosasa,T., Voyno-Yasenetskaya,T. and Le Breton,G.C. Protein kinase A-mediated phosphorylation of the Galpha13 switch I region alters the G alpha beta gamma13-G protein-coupled receptor complex and inhibits Rho activation. J. Biol. Chem. 278, 124-130 2003.
- Li, Zhang G, Le Breton G.C., Gao X, Malik AB, Du X: Two waves of platelet secretion induced by thromboxane A2 receptor and a critical role for PI 3-kinases. J. Biol. Chem. 278: 30725-30731, 2003.
- Huang, J-S., Lin, X., Ramamurthy, S. and Le Breton, G.C.: Cell signaling through thromboxane A2 receptors. Cell Signaling 16: 521-33, 2004.
- Lin, X., Ramamurthy, S. and Le Breton, G.C.:Thromboxane A2 Receptor-Mediated Cell Proliferation, Survival, and Gene Expression in Oligodendrocytes. J. Neurochem.93:257-68, 2005.
- Huang, J-S., Dong, L. and Le Breton, G.C.: Mass dependent signaling between G protein coupled receptors. Cell Signaling, 18:564-76, 2005.
- Ramamurthy, S., Mir, F. Gould, R.M. and Le Breton, G.C: Characterization of thromboxane A2 receptor signaling in developing rat oligodendrocytes: Nuclear receptor localization and stimulation of myelin basic protein expression. J.Neuroscience Res. 84: 1402-14, 2006.
- Khasawneh, F.T., Huang, J-S., Turek, J.W. and Le Breton, G.C.: Differential mapping of the amino acids mediating agonist and antagonist coordination with the human thromboxane A2 receptor protein. J. Biol. Chem. 281: 26951-65, 2006.
- Huang, J-S., Dong, L., Kozasa, T. and Le Breton, G.C.: Signaling through G13 Switch Region I is essential for PAR1-mediated human platelet shape change, aggregation and secretion. J. Biol. Chem., 2007 (in Press). (URL: http//www.jbc.org/cgi/content/abstract/M605678200v1).