Prokineticin receptors 1 and 2 (PKR1 and PKR2, encoded by PROKR1 and PROKR2) are closely related class A G protein-coupled receptors activated by the endogenous peptides prokineticin-1 and prokineticin-2. Both receptors can couple to Gq/11, leading to phospholipase C activation and intracellular calcium mobilization. PKR1 is expressed predominantly in peripheral tissues, including the cardiovascular and gastrointestinal systems, and is also found in immune cells. PKR2 is prominent in the central nervous system, particularly in olfactory and hypothalamic circuits, and is also expressed in peripheral tissues. The prokineticin system contributes to angiogenesis, gastrointestinal motility, inflammation, and pain, while PKR2 has established roles in circadian signaling and reproductive development. Loss-of-function variants in PROKR2 can impair receptor trafficking or signaling and are associated with congenital hypogonadotropic hypogonadism, including Kallmann syndrome. The small molecule IS20 is a selective PKR1 agonist, while compounds such as PKRA7 have been used as prokineticin receptor antagonists in preclinical studies. No drug acting directly at either prokineticin receptor has been reported to enter clinical trials or receive approval for therapeutic use.
PKR1 (non-phospho), PKR1 Prostanoid Receptor...