Prokineticin receptor 2

Prokineticin receptor 2

The Prokineticin receptor 2 (PKR2) is a G protein-coupled receptor that plays a crucial role in various physiological processes. It is encoded by the PROKR2 gene and is primarily expressed in the central nervous system, particularly in the hypothalamus.

Structure

PKR2 belongs to the rhodopsin-like family of G protein-coupled receptors. It consists of seven transmembrane domains, an extracellular N-terminus, and an intracellular C-terminus. The receptor undergoes conformational changes upon ligand binding, leading to the activation of downstream signaling pathways.

Function

PKR2 is the receptor for prokineticins, a family of small secreted proteins that regulate diverse biological functions. Upon binding to PKR2, prokineticins activate intracellular signaling cascades, including the Gαq/11 and Gαs pathways. These pathways mediate various physiological processes, such as neurogenesis, angiogenesis, circadian rhythm regulation, and reproductive functions.

Role in Reproduction

PKR2 is essential for normal reproductive development and function. Mutations in the PROKR2 gene have been associated with reproductive disorders, including Kallmann syndrome and idiopathic hypogonadotropic hypogonadism. These conditions are characterized by delayed or absent puberty, impaired sense of smell, and infertility. The loss of PKR2 function disrupts the release of gonadotropin-releasing hormone (GnRH), which is crucial for the initiation of puberty and the regulation of reproductive processes.

Role in Circadian Rhythm Regulation

PKR2 is also involved in the regulation of circadian rhythms. It is expressed in the suprachiasmatic nucleus (SCN), the master pacemaker of the circadian system. Activation of PKR2 in the SCN influences the synchronization of biological rhythms with the external light-dark cycle. Disruptions in PKR2 signaling have been linked to sleep disorders and disturbances in the sleep-wake cycle.

Clinical Implications

The role of PKR2 in reproductive and circadian functions makes it an attractive target for therapeutic interventions. Modulating PKR2 activity could potentially help in the treatment of reproductive disorders, such as infertility and delayed puberty. Additionally, targeting PKR2 signaling may offer new avenues for managing sleep disorders and circadian rhythm-related conditions.