The BBVA Foundation Frontiers of Knowledge Award in Biomedicine goes to Robert J. Lefkowitz for his discoveries of the seven transmembrane receptors (G protein-coupled receptors), the largest, most versatile and most therapeutically accessible receptor signaling system, and of the general mechanism of their regulation. (Receptors are the cellular macromolecules with which biological active substances initially interact on the surface of cells).
Apart from isolating the first members of this class of receptors, and showing that it was indeed a very large superfamily (represented by more than 1000 genes), he showed the general principles of how they work through biochemical analysis and structural biology. The determination of the structure of one protein, the beta adrenergic receptor, was a technical tour de force, because of its low abundance, but when he was able to compare it to the structure of other receptors this revealed the general principles of how they all work, providing the molecular basis by which signals from the environment are transduced across the cell membrane to evoke cellular responses: cell proliferation, differentiation, death, secretion, excitability and movement.
The receptors receive a broad spectrum of signals from outside the body, such as light, odors, tastes, and inside the body, such as hormones, cytokines and major neurotransmitters, such as serotonin, dopamine, GABA and glutamate. Indeed, they encompass a large proportion of the adaptive capabilities of living organisms.
Approximately 50% of current drugs target members of this receptor superfamily, as agonists or antagonists. The work has led to treatments for cardiovascular disease, such as beta-blockers. His studies have also led to an understanding of how drugs and hormones can lose their effect in patients due to changes in the receptors.”