The targetable G protein proteome: where is the next generation of drug targets?

Abstract

G protein-coupled signaling systems are the most important targets for therapeutic drugs, most of which are ligands for heptahelical receptors (7TM-R). A single receptor can activate various signaling pathways in different cells; consequently, drugs that target the receptor binding site are not necessarily specific for particular pathways. However, other downstream signaling partners that interact with heptahelical receptors can be unique for a given pathway and peptide motifs that are involved in these interactions are potential targets for the development of drugs with greater specificity and fewer side effects. Furthermore, it is becoming apparent that these systems are organized as protein complexes, making proteomic techniques ideal tools for identifying system components.