Prokineticin receptor 2 explained

Prokineticin receptor 2 (PKR₂), is a dimeric^[1] G protein-coupled receptor encoded by the PROKR2 gene in humans.

Function

Prokineticins are secreted proteins that can promote angiogenesis and induce strong gastrointestinal smooth muscle contraction. The protein encoded by this gene is an integral membrane protein and G protein-coupled receptor for prokineticins. PKR₂ is composed of 384 amino acids. Asparagine residues at position 7 and 27 undergo N-linked glycosylation. Cysteine residues at position 128 and 208 form a disulfide bond. The encoded protein is similar in sequence to GPR73, another G protein-coupled receptor for prokineticins.^[2] PKR₂ is also linked to mammalian circadian rhythm.^[3] Levels of PKR₂ mRNA fluctuate in the suprachiasmatic nucleus, increasing during the day and decreasing at night.

Mutations in the PROKR2 (also known as KAL3) gene have been implicated in hypogonadotropic hypogonadism and gynecomastia.^[4] Total loss of PKR₂ in mice leads to spontaneous torpor usually beginning at dusk and lasting for 8 hours on average.^[5]

PKR₂ functions as a G protein-coupled receptor, thus it has a signaling cascade when it's ligand binds. PKR₂ is a Gq-coupled protein, so when the ligand binds, beta-type phospholipase C is activated which creates inositol triphosphate. This then triggers calcium release inside the cell.^[6]

See also

• Prokineticin receptor
• Kallmann syndrome

References

Further reading

• Lin DC, Bullock CM, Ehlert FJ, Chen JL, Tian H, Zhou QY . Identification and molecular characterization of two closely related G protein-coupled receptors activated by prokineticins/endocrine gland vascular endothelial growth factor . The Journal of Biological Chemistry . 277 . 22 . 19276–19280 . May 2002 . 11886876 . 10.1074/jbc.M202139200 . 22935718 . free .
• Soga T, ((Matsumoto Si)), Oda T, Saito T, Hiyama H, Takasaki J, Kamohara M, Ohishi T, Matsushime H, Furuichi K . 6 . Molecular cloning and characterization of prokineticin receptors . Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression . 1579 . 2–3 . 173–179 . December 2002 . 12427552 . 10.1016/S0167-4781(02)00546-8 .
• Battersby S, Critchley HO, Morgan K, Millar RP, Jabbour HN . Expression and regulation of the prokineticins (endocrine gland-derived vascular endothelial growth factor and Bv8) and their receptors in the human endometrium across the menstrual cycle . The Journal of Clinical Endocrinology and Metabolism . 89 . 5 . 2463–2469 . May 2004 . 15126578 . 10.1210/jc.2003-032012 . free .
• Pasquali D, Rossi V, Staibano S, De Rosa G, Chieffi P, Prezioso D, Mirone V, Mascolo M, Tramontano D, Bellastella A, Sinisi AA . 6 . The endocrine-gland-derived vascular endothelial growth factor (EG-VEGF)/prokineticin 1 and 2 and receptor expression in human prostate: Up-regulation of EG-VEGF/prokineticin 1 with malignancy . Endocrinology . 147 . 9 . 4245–4251 . September 2006 . 16763065 . 10.1210/en.2006-0614 .
• Dodé C, Teixeira L, Levilliers J, Fouveaut C, Bouchard P, Kottler ML, Lespinasse J, Lienhardt-Roussie A, Mathieu M, Moerman A, Morgan G, Murat A, Toublanc JE, Wolczynski S, Delpech M, Petit C, Young J, Hardelin JP . 6 . Kallmann syndrome: mutations in the genes encoding prokineticin-2 and prokineticin receptor-2 . PLOS Genetics . 2 . 10 . e175 . October 2006 . 17054399 . 1617130 . 10.1371/journal.pgen.0020175 . free .

External links

• GeneReviews/NCBI/NIH/UW entry on Kallmann syndrome
• Web site: Prokineticin Receptors: PKR₂ . IUPHAR Database of Receptors and Ion Channels . International Union of Basic and Clinical Pharmacology . 2008-12-09 . 2009-07-17 . https://web.archive.org/web/20090717115411/http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=3017 . dead .

Notes and References

1. Sposini S, Caltabiano G, Hanyaloglu AC, Miele R . Identification of transmembrane domains that regulate spatial arrangements and activity of prokineticin receptor 2 dimers . Molecular and Cellular Endocrinology . 399 . 362–372 . January 2015 . 25449422 . 10.1016/j.mce.2014.10.024 . 10044/1/31246 . 13491537 . free .
2. Web site: Entrez Gene: PROKR2 prokineticin receptor 2.
3. Masumoto KH, Nagano M, Takashima N, Hayasaka N, Hiyama H, Matsumoto S, Inouye ST, Shigeyoshi Y . 6 . Distinct localization of prokineticin 2 and prokineticin receptor 2 mRNAs in the rat suprachiasmatic nucleus . The European Journal of Neuroscience . 23 . 11 . 2959–2970 . June 2006 . 16819985 . 10.1111/j.1460-9568.2006.04834.x . 20510543 .
4. Narula HS, Carlson HE . Gynaecomastia--pathophysiology, diagnosis and treatment . Nature Reviews. Endocrinology . 10 . 11 . 684–698 . November 2014 . 25112235 . 10.1038/nrendo.2014.139 . 40159424 .
5. Jethwa PH, I'Anson H, Warner A, Prosser HM, Hastings MH, Maywood ES, Ebling FJ . Loss of prokineticin receptor 2 signaling predisposes mice to torpor . American Journal of Physiology. Regulatory, Integrative and Comparative Physiology . 294 . 6 . R1968–R1979 . June 2008 . 18417646 . 2735815 . 10.1152/ajpregu.00778.2007 .
6. Martin C, Balasubramanian R, Dwyer AA, Au MG, Sidis Y, Kaiser UB, Seminara SB, Pitteloud N, Zhou QY, Crowley WF . 6 . The role of the prokineticin 2 pathway in human reproduction: evidence from the study of human and murine gene mutations . Endocrine Reviews . 32 . 2 . 225–246 . April 2011 . 21037178 . 3365793 . 10.1210/er.2010-0007 .