The Prokineticins (PK1 and PK2) are a pair of cysteine-rich secreted peptides with broad physiological functions including gastrointestinal motility, angiogenesis, hematopoiesis and circadian rhythms regulation.

The biological effects of PK1 and PK2 are mediated by two highly homologous receptors termed Prokineticin receptor 1 (PKR1) and Prokineticin receptor 2 (PKR2) that belong to the 7-transmembrane domain, G-protein coupled receptor (GPCR) superfamily. Both PK ligands activate the two PK receptors with similar potency.¹

PKR2 receptors couple to G_q/G₁₁ proteins leading to phospholipase C activation, inositol phosphate production and calcium mobilization.

The distribution of PKR2 is relatively restricted with high expression levels in the brain, spinal cord and dorsal root ganglions, in organs of the reproductive system and in endocrine tissues such as the thyroid, pituitary and adrenal glands.¹

The PK2 ligand has been shown to be involved in the regulation of circadian rhythms of physiological and behavioral processes in mammals, probably through signaling via PKR2 which is highly expressed in the suprachiasmatic nucleus (SCN), an area of the brain that controls circadian rhythm processes.²

In addition, loss-of-function mutations in the PKR2 gene have been associated with Kallmann Syndrome, a condition characterized by idiopathic hypogonadotropic hypogonadism (IHH) in combination with anosmia, a compromised sense of smell.³