Abstract
Secreted peptides have been implicated in diverse physiological functions. Prokineticins are a pair of regulatory peptides that signal through two highly homologous G protein-coupled receptors. Prokineticins possess a unique structural motif of five disulfide bonds and conserved N-terminal stretches. Diverse biological functions, ranging from development to adult physiology, have been attributed to prokineticins. Herein we provide an overview of current knowledge of this interesting pair of regulatory peptides.
Access provided by Autonomous University of Puebla. Download to read the full chapter text
Chapter PDF
Similar content being viewed by others
References
Abbott NJ (2000) Inflammatory mediators and modulation of blood-brain barrier permeability. Cell Mol Neurobiol 20:131–147
Altman J (1969) Autoradiographic and histological studies of postnatal neurogenesis. IV. Cell proliferation and migration in the anterior forebrain, with special reference to persisting neurogenesis in the olfactory bulb. J Comp Neurol 137:433–457
Bassil AK, Dass NB, Murray CD, Muir A, Sanger GJ (2005) Prokineticin-2, motilin, ghrelin and metoclopramide: prokinetic utility in mouse stomach and colon. Eur J Pharmacol 524:138–144
Battersby S, Critchley HO, Morgan K, Millar RP, Jabbour HN (2004) 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. J Clin Endocrinol Metab 89:2463–2469
Bertrand N, Castro DS, Guillemot F (2002) Proneural genes and the specification of neural cell types. Nat Rev Neurosci 3:517–530
Boisbouvier J, Albrand JP, Blackledge M, Jaquinod M, Schweitz H, Lazdunski M, Marion D (1998) A structural homologue of colipase in black mamba venom revealed by NMR floating disulphide bridge analysis. J Mol Biol 283:205–219
Borbely AA (1982) A two process model of sleep regulation. Hum Neurobiol 1:195–204
Borbely AA, Achermann P, Trachsel L, Tobler I (1989) Sleep initiation and initial sleep intensity: interactions of homeostatic and circadian mechanisms. J Biol Rhythms 4:149–160
Bullock CM, Li JD, Zhou QY (2004) Structural determinants required for the bioactivities of prokineticins and identification of prokineticin receptor antagonists. Mol Pharmacol 65:582–588
Bunger MK, Wilsbacher LD, Moran SM, Clendenin C, Radcliffe LA, Hogenesch JB, Simon MC, Takahashi JS, Bradfield CA (2000) Mop3 is an essential component of the master circadian pacemaker in mammals. Cell 103:1009–1017
Caterina MJ, Julius D (2001) The vanilloid receptor: a molecular gateway to the pain pathway. Annu Rev Neurosci 24:487–517
Chen J, Kuei C, Sutton S, Wilson S, Yu J, Kamme F, Mazur C, Lovenberg TW, Liu C (2005) Identification and Pharmacological Characterization of Prokineticin 2{beta} as a Selective Ligand for Prokineticin Receptor 1. Mol Pharmacol 67:2070–2076
Cheng MY, Bullock CM, Li C, Lee AG, Bermak JC, Belluzzi J, Weaver DR, Leslie FM, Zhou QY (2002) Prokineticin 2 transmits the behavioural circadian rhythm of the suprachiasmatic nucleus. Nature 417:405–410
Cheng MY, Bittman EL, Hattar S, Zhou QY (2005) Regulation of prokineticin 2 expression by light and the circadian clock. BMC Neurosci 6:17–27
Cheng MY, Leslie FM, Zhou QY (2006) Expression of prokineticins and their receptors in the adult mouse brain. J Comp Neurol 498:796–809
Cottrell GT, Zhou QY, Ferguson AV (2004) Prokineticin 2 modulates the excitability of subfornical organ neurons. J Neurosci 24:2375–2379
Damiola F, Le Minh N, Preitner N, Kornmann B, Fleury-Olela F, Schibler U (2000) Restricted feeding uncouples circadian oscillators in peripheral tissues from the central pacemaker in the suprachiasmatic nucleus. Genes Dev 14:2950–2961
Dode 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 (2006) Kallmann syndrome: mutations in the genes encoding prokineticin-2 and prokineticin receptor-2. PLoS Genet 2:e175
Dorsch M, Qiu Y, Soler D, Frank N, Duong T, Goodearl A, O'Neil S, Lora J, Fraser CC (2005) PK1/EG-VEGF induces monocyte differentiation and activation. J Leukoc Biol 78:426–434
Dudley CA, Erbel-Sieler C, Estill SJ, Reick M, Franken P, Pitts S, McKnight SL (2003) Altered patterns of sleep and behavioral adaptability in NPAS2-deficient mice. Science 301:379–383
Eastman CI, Mistlberger RE, Rechtschaffen A (1984) Suprachiasmatic nuclei lesions eliminate circadian temperature and sleep rhythms in the rat. Physiol Behav 32:357–368
Edgar DM, Dement WC, Fuller CA (1993) Effect of SCN lesions on sleep in squirrel monkeys: evidence for opponent processes in sleep-wake regulation. J Neurosci 13:1065–1079
Ferrara N, Frantz G, LeCouter J, Dillard-Telm L, Pham T, Draksharapu A, Giordano T, Peale F (2003) Differential expression of the angiogenic factor genes vascular endothelial growth factor (VEGF) and endocrine gland-derived VEGF in normal and polycystic human ovaries. Am J Pathol 162:1881–1893
Ferrara N, LeCouter J, Lin R, Peale F (2004) EG-VEGF and Bv8: a novel family of tissue-restricted angiogenic factors. Biochim Biophys Acta 1654:69–78
Fraser HM, Bell J, Wilson H, Taylor PD, Morgan K, Anderson RA, Duncan WC (2005) Localization and quantification of cyclic changes in the expression of endocrine gland vascular endothelial growth factor in the human corpus luteum. J Clin Endocrinol Metab 90:427–434
Gage FH (2000) Mammalian neural stem cells. Science 287:1433–1438
Gooley JJ, Schomer A, Saper CB (2006) The dorsomedial hypothalamic nucleus is critical for the expression of food-entrainable circadian rhythms. Nat Neurosci 9:398–407
Hoffmann P, Feige JJ, Alfaidy N (2006) Expression and oxygen regulation of endocrine gland-derived vascular endothelial growth factor/prokineticin-1 and its receptors in human placenta during early pregnancy. Endocrinol 147:1675–1684
Hoogerwerf WA (2006) Prokineticin 1 inhibits spontaneous giant contractions in the murine proximal colon through nitric oxide release. Neurogastroenterol Motil 18:455–463
Hu WP, Li JD, Zhang C, Luo G, Amadesi S, Bunnett N, Zhou QY (2006) Impaired pain sensation in mice lacking the prokineticin 2. Mol Pain 2:35
Hu WP, Li JD, Zhang C, Boehmer L, Siegel JM, Zhou QY (2007) Altered circadian and homeostatic sleep regulation in prokineticin 2-deficient mice. Sleep 30:247–256
Joubert FJ, Strydom DJ (1980) Snake venom. The amino acid sequence of protein A from Dendroaspis polylepis polylepis (black mamba) venom. Hoppe Seylers. Z Physiol Chem 361:1787–1794
Kaser A, Winklmayr M, Lepperdinger G, Kreil G (2003) The AVIT protein family. Secreted cysteine-rich vertebrate proteins with diverse functions. EMBO Rep 4:469–473
Kaplan MS, Hinds JW (1977) Neurogenesis in the adult rat: electron microscopic analysis of light radioautographs. Science 197:1092–1094
Kisliouk T, Levy N, Hurwitz A, Meidan R (2003) Presence and regulation of endocrine gland vascular endothelial growth factor/prokineticin-1 and its receptors in ovarian cells. J Clin Endocrinol Metab 88:3700–3707
Kisliouk T, Podlovni H, Meidan R (2005a) Unique expression and regulatory mechanisms of EG-VEGF/prokineticin-1 and its receptors in the corpus luteum. Ann Anat 187:529–537
Kisliouk T, Podlovni H, Spanel-Borowski K, Ovadia O, Zhou QY, Meidan R (2005b) Prokineticins (endocrine gland-derived vascular endothelial growth factor and BV8) in the bovine ovary: expression and role as mitogens and survival factors for corpus luteum-derived endothelial cells. Endocrinol 146:3950–3958
Kisliouk T, Friedman A, Klipper E, Zhou QY, Schams D, Alfaidy N, Meidan R (2007) Expression pattern of prokineticin 1 and its receptors in bovine ovaries during the estrous cycle: involvement in corpus luteum regression and follicular atresia. Biol Reprod 76:749–758
Klein DC, Moore RY, Reppert SM (eds) (1991) Suprachiasmatic nucleus: the mind's clock. Oxford University Press, Oxford, UK
Kniesel U, Wolburg H (2000) Tight junctions of the blood-brain barrier. Cell Mol Neurobiol 20:57–76
Lambert CM, Machida KK, Smale L, Nunez AA, Weaver DR (2005) Analysis of the Prokineticin 2 System in a Diurnal Rodent, the Unstriped Nile Grass Rat (Arvicanthis niloticus). J Biol Rhythms 20:206–218
Laposky A, Easton A, Dugovic C, Walisser J, Bradfield C, Turek F (2005) Deletion of the mammalian circadian clock gene BMAL1/Mop3 alters baseline sleep architecture and the response to sleep deprivation. Sleep 28:395–409
LeCouter J, Kowalski J, Foster J, Hass P, Zhang Z, Dillard-Telm L, Frantz G, Rangell L, DeGuzman L, Keller GA, Peale F, Gurney A, Hillan KJ, Ferrara N (2001) Identification of an angiogenic mitogen selective for endocrine gland endothelium. Nature 412:877–884
LeCouter J, Ferrara N (2003a) EG-VEGF and Bv8. A novel family of tissue-selective mediators of angiogenesis, endothelial phenotype, and function. Trends Cardiovasc Med 13:276–282
LeCouter J, Lin R, Tejada M, Frantz G, Peale F, Hillan KJ, Ferrara N (2003b) The endocrine-gland-derived VEGF homologue Bv8 promotes angiogenesis in the testis: Localization of Bv8 receptors to endothelial cells. Proc Natl Acad Sci USA 100:2685–2690
LeCouter J, Lin R, Frantz G, Zhang Z, Hillan K, Ferrara N (2003c) Mouse endocrine gland-derived vascular endothelial growth factor: a distinct expression pattern from its human ortholog suggests different roles as a regulator of organ-specific angiogenesis. Endocrinol 144:2606–2616
LeCouter J, Zlot C, Tejada M, Peale F, Ferrara N (2004) Bv8 and endocrine gland-derived vascular endothelial growth factor stimulate hematopoiesis and hematopoietic cell mobilization. Proc Natl Acad Sci USA 101:16813–16818
Lewis KE (2004) Prokineticin-2, a potential novel protein therapeutic increases post-operative gastric and intestinal motility in rats. Gastroenterology 126(2):A641
Li M, Bullock CM, Knauer DJ, Ehlert FJ, Zhou QY (2001) Identification of two prokineticin cDNAs: recombinant proteins potently contract gastrointestinal smooth muscle. Mol Pharmacol 59:692–698
Li JD, Hu WP, Boehmer LN, Cheng MY, Lee AG, Jilek A, Siegel JM, Zhou QY (2006) Attenuated Circadian Rhythms in Mice Lack the Prokineticin 2 Gene. J Neurosci 26:11615–11623
Lin DC, Bullock CM, Ehlert FJ, Chen JL, Tian H, Zhou QY (2002a) Identification and molecular characterization of two closely related G protein-coupled receptors activated by prokineticins/endocrine gland vascular endothelial growth factor. J Biol Chem 277:19276–19280
Lin R, LeCouter J, Kowalski J, Ferrara N (2002b) Characterization of endocrine gland-derived vascular endothelial growth factor signaling in adrenal cortex capillary endothelial cells. J Biol Chem 277:8724–8729
Lois C, Alvarez-Buylla A (1994) Long-distance neuronal migration in the adult mammalian brain. Science 264:1145–1148
Lowrey PL, Takahashi JS (2004) Mammalian circadian biology: elucidating genome-wide levels of temporal organization. Annu Rev Genomics Hum Genet 5:407–441
Luskin MB (1993) Restricted proliferation and migration of postnatally generated neurons derived from the forebrain subventricular zone. Neuron 11:173–189
Maldonado-Perez D, Evans J, Denison F, Millar RP, Jabbour HN (2007) Potential roles of the prokineticins in reproduction. Trends Endocrinol Metab 18:66–72
Martucci C, Franchi S, Giannini E, Tian H, Melchiorri P, Negri L, Sacerdote P (2006) Bv8, the amphibian homologue of the mammalian prokineticins, induces a proinflammatory phenotype of mouse macrophages. Br J Pharmacol 147:225–234
Masuda Y, Takatsu Y, Terao Y, Kumano S, Ishibashi Y, Suenaga M, Abe M, Fukusumi S, Watanabe T, Shintani Y, Yamada T, Hinuma S, Inatomi N, Ohtaki T, Onda H, Fujino M (2002) Isolation and identification of EG-VEGF/prokineticins as cognate ligands for two orphan G-protein-coupled receptors. Biochem Biophys Res Commun 293:396–402
Masumoto KH, Nagano M, Takashima N, Hayasaka N, Hiyama H, Matsumoto S, Inouye ST, Shigeyoshi Y (2006) Distinct localization of prokineticin 2 and prokineticin receptor 2 mRNAs in the rat suprachiasmatic nucleus. Eur J Neurosci 23:2959–2970
Matsumoto S, Yamazaki C, Masumoto KH, Nagano M, Naito M, Soga T, Hiyama H, Matsumoto M, Takasaki J, Kamohara M, Matsuo A, Ishii H, Kobori M, Katoh M, Matsushime H, Furuichi K, Shigeyoshi Y (2006) Abnormal development of the olfactory bulb and reproductive system in mice lacking prokineticin receptor PKR2. Proc Natl Acad Sci USA 103:4140–4145
Mistlberger RE, Bergmann BM, Waldenar W, Rechtschaffen A (1983) Recovery sleep following sleep deprivation in intact and suprachiasmatic nuclei-lesioned rats. Sleep 6:217–233
Mollay C, Wechselberger C, Mignogna G, Negri L, Melchiorri P, Barra D, Kreil G (1999) Bv8, a small protein from frog skin and its homologue from snake venom induce hyperalgesia in rats. Eur J Pharmacol 374:189–196
Morton AJ, Wood NI, Hastings MH, Hurelbrink C, Barker RA, Maywood ES (2005) Disintegration of the sleep-wake cycle and circadian timing in Huntington's disease. J Neurosci 25:157–163
Mouret J, Coindet J, Debilly G, Chouvet G (1978) Suprachiasmatic nuclei lesions in the rat: alterations in sleep circadian rhythms. Electroencephalogr Clin Neurophysiol 45:402–408
Negri L, Lattanzi R, Giannini E, Metere A, Colucci M, Barra D, Kreil G, Melchiorri P (2002) Nociceptive sensitization by the secretory protein Bv8. Br J Pharmacol 137:1147–1154
Negri L, Lattanzi R, Giannini E, De Felice M, Colucci A, Melchiorri P (2004) Bv8, the amphibian homologue of the mammalian prokineticins, modulates ingestive behaviour in rats. Br J Pharmacol 142:181–191
Negri L, Lattanzi R, Giannini E, Colucci MA, Mignogna G, Barra D, Grohovaz F, Codazzi F, Kaiser A, Kreil G, Melchiorri P (2005) Biological activities of Bv8 analogues. Br J Pharmacol 146:625–632
Negri L, Lattanzi R, Giannini E, Colucci M, Margheriti F, Melchiorri P, Vellani V, Tian H, De Felice M, Porreca F (2006) Impaired nociception and inflammatory pain sensation in mice lacking the prokineticin receptor PKR1: focus on interaction between PKR1 and the capsaicin receptor TRPV1 in pain behavior. J Neurosci 26:6716–6727
Negri L, Lattanzi R, Giannini E, Melchiorri P (2007) Bv8/Prokineticin proteins and their receptors. Life Sci 81:1103–1116
Ng KL, Li JD, Cheng MY, Leslie FM, Lee AG, Zhou QY (2005) Dependence of olfactory bulb neurogenesis on prokineticin 2 signaling. Science 308:1923–1927
Ngan ES, Sit FY, Lee K, Miao X, Yuan Z, Wang W, Nicholls JM, Wong KK, Garcia-Barcelo M, Lui VC, Tam PK (2007) Implications of endocrine gland-derived vascular endothelial growth factor/prokineticin-1 signaling in human neuroblastoma progression. Clin Cancer Res 13:868–875
Pasquali D, Rossi V, Staibano S, De Rosa G, Chieffi P, Prezioso D, Mirone V, Mascolo M, Tramontano D, Bellastella A, Sinisi AA (2006) 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. Endocrinol 147:4245–4251
Pitteloud N, Zhang C, Pignatelli D, Li JD, Raivio T, Cole LW, Plummer L, Jacobson-Dickman EE, Mellon PL, Zhou QY, Crowley WF Jr (2007) Loss-of-function mutation in the prokineticin 2 gene causes Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism. Proc Natl Acad Sci USA 104:17447–17452
Pitts S, Perone E, Silver R (2003) Food-entrained circadian rhythms are sustained in arrhythmic Clk/Clk mutant mice. Am J Physiol Regul Integr Comp Physiol 285:R57–R67
Podlovni H, Ovadia O, Kisliouk T, Klipper E, Zhou QY, Friedman A, Alfaidy N, Meidan R (2006) Differential expression of prokineticin receptors by endothelial cells derived from different vascular beds: a physiological basis for distinct endothelial function. Cell Physiol Biochem 18:315–326
Prosser HM, Bradley A, Chesham JE, Ebling FJ, Hastings MH, Maywood ES (2007) Prokineticin receptor 2 (Prokr2) is essential for the regulation of circadian behavior by the suprachiasmatic nuclei. Proc Natl Acad Sci USA 104:648–653
Reppert SM, Weaver DR (2002) Coordination of circadian timing in mammals. Nature 418:935–941
Schweitz H, Bidard JN, Lazdunski M (1990) Purification and pharmacological characterization of peptide toxins from the black mamba (Dendroaspis polylepis) venom. Toxicon 28:847–856
Schweitz H, Pacaud P, Diochot S, Moinier D, Lazdunski M (1999) MIT(1), a black mamba toxin with a new and highly potent activity on intestinal contraction. FEBS Lett 461:183–188
Soderhall I, Kim YA, Jiravanichpaisal P, Lee SY, Soderhall K (2005) An ancient role for a prokineticin domain in invertebrate hematopoiesis. J Immunol 174:6153–6160
Soga T, Matsumoto S, Oda T, Saito T, Hiyama H, Takasaki J, Kamohara M, Ohishi T, Matsushime H, Furuichi K (2002) Molecular cloning and characterization of prokineticin receptors. Biochim Biophys Acta 1579:173–179
Stokkan KA, Yamazaki S, Tei H, Sakaki Y, Menaker M (2001) Entrainment of the circadian clock in the liver by feeding. Science 291:490–493
Tanaka N, Ikawa M, Mata NL, Verma IM (2006) Choroidal neovascularization in transgenic mice expressing prokineticin 1: an animal model for age-related macular degeneration. Mol Ther 13:609–616
Tobler I, Borbely AA, Groos G (1983) The effect of sleep deprivation on sleep in rats with suprachiasmatic lesions. Neurosci Lett 42:49–54
Trachsel L, Edgar DM, Seidel WF, Heller HC, Dement WC (1992) Sleep homeostasis in suprachiasmatic nuclei-lesioned rats: effects of sleep deprivation and triazolam administration. Brain Res 589:253–261
Vellani V, Colucci M, Lattanzi R, Giannini E, Negri L, Melchiorri P, McNaughton PA (2006) Sensitization of transient receptor potential vanilloid 1 by the prokineticin receptor agonist Bv8. J Neurosci 26:5109–5116
Vitaterna MH, King DP, Chang AM, Kornhauser JM, Lowrey PL, McDonald JD, Dove WF, Pinto LH, Turek FW, Takahashi JS (1994) Mutagenesis and mapping of a mouse gene, Clock, essential for circadian behavior. Science 264:719–725
Wechselberger C, Puglisi R, Engel E, Lepperdinger G, Boitani C, Kreil G (1999) The mammalian homologues of frog Bv8 are mainly expressed in spermatocytes. FEBS Lett 462:177–181
Wierman ME, Pawlowski JE, Allen MP, Xu M, Linseman DA, Nielsen-Preiss S (2004) Molecular mechanisms of gonadotropin-releasing hormone neuronal migration. Trends Endocrinol Metab 15:96–102
Wisor JP, O'Hara BF, Terao A, Selby CP, Kilduff TS, Sancar A, Edgar DM, Franken P (2002) A role for cryptochromes in sleep regulation. BMC Neurosci 3:20
Wurts SW, Edgar DM (2000) Circadian and homeostatic control of rapid eye movement (REM) sleep: promotion of REM tendency by the suprachiasmatic nucleus. J Neurosci 20:4300–4310
Yamazaki S, Numano R, Abe M, Hida A, Takahashi R, Ueda M, Block GD, Sakaki Y, Menaker M, Tei H (2000) Resetting central and peripheral circadian oscillators in transgenic rats. Science 288:682–685
Yuill EA, Ferri CC, Zhou QY, Ferguson AV (2007) Prokineticin 2 Depolarizes Paraventricular Nucleus Neurons: Cellular Correlates for Circadian Regulation of Autonomic Function. Eur J Neurosci 25:425–434
Zhang C, Ng KL, Li JD, He F, Anderson DJ, Sun YE, Zhou QY (2007) Prokineticin 2 is a target gene of proneural basic helix-loop-helix factors for olfactory bulb neurogenesis. J Biol Chem 282:6917–6921
Zhang L, Yang N, Conejo-Garcia JR, Katsaros D, Mohamed-Hadley A, Fracchioli S, Schlienger K, Toll A, Levine B, Rubin SC, Coukos G (2003) Expression of endocrine gland-derived vascular endothelial growth factor in ovarian carcinoma. Clin Cancer Res 9:264–272
Zhou QY, Cheng MY (2005) Prokineticin 2 and circadian clock output. FEBS J 272:5703–5709
Zhou QY (2006) The prokineticins: a novel pair of regulatory peptides. Mol Interv 6:330–338
Author information
Authors and Affiliations
Corresponding author
Editor information
Rights and permissions
Copyright information
© 2008 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Zhou, QY., Meidan, R. (2008). Biological Function of Prokineticins. In: Civelli, O., Zhou, QY. (eds) Orphan G Protein-Coupled Receptors and Novel Neuropeptides. Results and Problems in Cell Differentiation, vol 46. Springer, Berlin, Heidelberg. https://doi.org/10.1007/400_2007_053
Download citation
DOI: https://doi.org/10.1007/400_2007_053
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-78350-3
Online ISBN: 978-3-540-78351-0
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)