G-protein-coupled receptors and signaling networks: emerging paradigms.

G-protein-coupled receptors (GPCRs) constitute the largest family of cell-surface molecules involved in signal transmission. These receptors play key physiological roles and their dysfunction results in several diseases. Recently, it has been shown that many of the cellular responses mediated by GPCRs do not involve the sole stimulation of conventional second-messenger-generating systems, but instead result from the functional integration of an intricate network of intracellular signaling pathways. Effectors for GPCRs that are independent of G proteins have now also been identified, thus changing the conventional view of the GPCR-heterotrimeric-G-protein-associated effector. The emerging information is expected to help elucidate the most basic mechanism by which these receptors exert their numerous physiological roles, in addition to determining why the perturbation of their function results in many pathological conditions.