Molecular and Cellular Signalling

Terence Hébert , Ph. D

Research in Dr. Hébert's laboratory centers on the determination of the mechanisms controlling specificity of signalling in cardiac cells.

Cells must discriminate among a plethora of signals and in many instances must be able to integrate signals coming from several different pathways. Thus, the cell must simultaneously facilitate this crosstalk between receptor pathways and paradoxically limit it in order to preserve specificity. The problem of specificity in GPCR signalling becomes apparent when one considers that there are hundreds of different receptors, 16 G protein a subunits, 5 Gb subunits and 12 Gg subunits as well as a large number of effectors and regulatory proteins. Our hypothesis is that the different signalling molecules form pre-assembled complexes which assure specificity and speed of response in the various pathways. These complexes and the interfaces between the different partners could be the targets for more effective therapeutic strategies.

Our long term goal is the development of drugs possessing much fewer side effects for the treatment of various cardiovascular diseases.

Publications

Rebois, R.V., Hébert, T.E. Protein complexes involved in signal transduction
mediated by heptahelical receptors, Receptors and Channels, 9 pages 169 à 194, 2003

Mirshahi, T., Robillard, L., Zhang, H., Hébert, T.E., Logothetis, D.E. G b residues that do not interact with Ga underlie agonist-independent activity of K + channels, J. Biol.Chem., 277, pages 7348 à 7355, 2002.

Lavoie, C., Mercier, J.-F., Salahpour, A., Umapathy, D., Breit, A. Villeneuve, L.-R., Zhu, W.-Z., Lakatta, E.G., Xiao, R.P., Bouvier, M., Hébert, T.E. b 1/ b 2-adrenergic receptor hetero-dimerization regulates b 2-adrenergic receptor internalization and ERK signalling efficacy, J. Biol. Chem., 277 pages 35402 à 35410, 2002

Lavine, N., Ethier, N., Oak, J.N., Pei, L., Liu, F., Trieu, P., Rebois, R.V., Bouvier, M.,  Hébert, T.E. and  Van Tol, H.H.M. (2002) Receptor/effector interactions in G protein-coupled receptor systems, J. Biol. Chem., 277 pages 46010 à 46019, 2002