DIVERSITY AND SELECTIVITY OF RECEPTOR-G PROTEIN-INTERACTION

Cells in a living organism communicate with each other through extrace llular molecules such as hormones, neurotransmitters, and growth facto rs. The majority of these molecules transmit their signal by interacti ng with a three-protein transmembrane signal transduction system whose single components interact sequentially and reversibly. Agonist bindi ng to a heptahelical receptor results in activation of heterotrimeric guanine nucleotide-binding proteins (G proteins) that modulate the act ivity of one or more effector systems. Considering that hundreds of G protein-coupled receptors transduce signals by interacting with a limi ted repertoire of G proteins, the question of specificity governing th e coupling of receptors to G proteins arises. The conceptualization of signal transduction pathways in a linear fashion (one receptor coupli ng to one G protein that activates one effector) is inadequate to expl ain experimental results. In the present review, G protein-mediated si gnal transduction is depicted as a complex signaling network with dive rgent and convergent pathways at each transduction level, i.e. recepto r, G protein, and effector. The recent realization that ''classical'' signaling pathways appear to be activated in parallel with signaling c ascades primarily described for growth factors and cytokines adds an a dditional level of intriguing complexity.