Interaction of prokineticin receptors with accessory proteins

G protein-coupled receptors (GPCRs) are transmembrane proteins that mediate the intracellular pathway of signals not only through heterotrimeric GTP-binding proteins (G proteins) but also through their associations with a variety of additional partner proteins. Prokineticin receptors 1 (PKR1) and 2 (PKR2) are new members of the GPCRs whose ligands are the novel chemokines prokineticin 1 (PK1) and prokineticin 2 (PK2). The multiplicity of G proteins coupled to PKRs, the ability of PKR2 to heterodimerize, the interaction of PKR2 with accessory proteins, and the existence of alternative splice isoforms of PKR2/PK2 explain the complexity of the system in the signal transduction pathway and, consequently, in the modulation of various physiological and pathological functions. Knowledge of these mechanisms provides the basis for the development of targeted drugs with therapeutic efficacy in PK-dependent diseases.