Gene Symbol: Prok2
Description: prokineticin 2
Alias: Bv8, PK2, Prok1, prokineticin-2, Bombina variegata 8 kD protein, Bombina variegata 8kDa protein, Bv 8 homolog (Bombina variegata), prokineticin 1, protein Bv8 homolog
Species: mouse
Products:     Prok2

Top Publications

  1. Cheng M, Bullock C, Li C, Lee A, Bermak J, Belluzzi J, et al. Prokineticin 2 transmits the behavioural circadian rhythm of the suprachiasmatic nucleus. Nature. 2002;417:405-10 pubmed
    ..Here we show that prokineticin 2 (PK2), a cysteine-rich secreted protein, functions as an output molecule from the SCN circadian clock...
  2. Xin H, Lu R, Lee H, Zhang W, Zhang C, Deng J, et al. G-protein-coupled receptor agonist BV8/prokineticin-2 and STAT3 protein form a feed-forward loop in both normal and malignant myeloid cells. J Biol Chem. 2013;288:13842-9 pubmed publisher
    Signaling pathways underlying BV8-mediated oncogenesis remain unknown. BV8-STAT3 forms a feed-forward loop in both normal and malignant myeloid cells and promotes tumor growth...
  3. Giannini E, Lattanzi R, Nicotra A, Campese A, Grazioli P, Screpanti I, et al. The chemokine Bv8/prokineticin 2 is up-regulated in inflammatory granulocytes and modulates inflammatory pain. Proc Natl Acad Sci U S A. 2009;106:14646-51 pubmed publisher
    Neutrophil migration into injured tissues is invariably accompanied by pain. Bv8/prokineticin 2 (PK2), a chemokine characterized by a unique structural motif comprising five disulfide bonds, is highly expressed in inflamed tissues ..
  4. Cheng M, Bittman E, Hattar S, Zhou Q. Regulation of prokineticin 2 expression by light and the circadian clock. BMC Neurosci. 2005;6:17 pubmed
    ..Previously we have shown that prokineticin 2 (PK2) is a clock-controlled gene that may function as a critical SCN output molecule responsible for circadian ..
  5. Li J, Hu W, Boehmer L, Cheng M, Lee A, Jilek A, et al. Attenuated circadian rhythms in mice lacking the prokineticin 2 gene. J Neurosci. 2006;26:11615-23 pubmed
    ..b>Prokineticin 2 (PK2), a clock-controlled gene that encodes a secreted protein, has been indicated as a candidate SCN clock ..
  6. Prosser H, Bradley A, Chesham J, Ebling F, Hastings M, Maywood E. Prokineticin receptor 2 (Prokr2) is essential for the regulation of circadian behavior by the suprachiasmatic nuclei. Proc Natl Acad Sci U S A. 2007;104:648-53 pubmed
    ..suggest a role for (unidentified) secreted factors, and one potential candidate is the SCN neuropeptide prokineticin 2 (Prok2)...
  7. Qu X, Zhuang G, Yu L, Meng G, Ferrara N. Induction of Bv8 expression by granulocyte colony-stimulating factor in CD11b+Gr1+ cells: key role of Stat3 signaling. J Biol Chem. 2012;287:19574-84 pubmed publisher
    Bv8, also known as prokineticin 2, has been characterized as an important mediator of myeloid cell mobilization and myeloid cell-dependent tumor angiogenesis. Bv8 expression is dramatically enhanced by G-CSF, both in vitro and in vivo...
  8. Shojaei F, Wu X, ZHONG C, Yu L, Liang X, Yao J, et al. Bv8 regulates myeloid-cell-dependent tumour angiogenesis. Nature. 2007;450:825-31 pubmed
    ..We have previously shown that the related EG-VEGF and Bv8 proteins, also known as prokineticin 1 (Prok1) and prokineticin 2 (Prok2), promote both tissue-specific angiogenesis and haematopoietic cell ..
  9. Ng K, Li J, Cheng M, Leslie F, Lee A, Zhou Q. Dependence of olfactory bulb neurogenesis on prokineticin 2 signaling. Science. 2005;308:1923-7 pubmed
    ..Here we show that secreted prokineticin 2 (PK2) functions as a chemoattractant for SVZ-derived neuronal progenitors...

More Information


  1. Prosser H, Bradley A, Caldwell M. Olfactory bulb hypoplasia in Prokr2 null mice stems from defective neuronal progenitor migration and differentiation. Eur J Neurosci. 2007;26:3339-44 pubmed
    ..of this, Prokr2-deficient cells expanded in vitro as neurospheres are incapable of migrating towards a source of recombinant human prokineticin 2 (PROK2). Together, these findings suggest an important role for Prokr2 in OB neurogenesis.
  2. Pitteloud N, Zhang C, Pignatelli D, Li J, Raivio T, Cole L, et al. Loss-of-function mutation in the prokineticin 2 gene causes Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism. Proc Natl Acad Sci U S A. 2007;104:17447-52 pubmed
    ..Therefore, we hypothesize that mutations in prokineticin 2 (PROK2) underlie some cases of KS in humans and that animals deficient in Prok2 would be hypogonadotropic...
  3. Wechselberger C, Puglisi R, Engel E, Lepperdinger G, Boitani C, Kreil G. The mammalian homologues of frog Bv8 are mainly expressed in spermatocytes. FEBS Lett. 1999;462:177-81 pubmed
    b>Bv8, a protein from skin secretions of Bombina variegata, reacts with receptors present in mammalian brain and intestine (Mollay et al. (1999) Eur. J. Pharmacol. 374, 189-196)...
  4. LeCouter J, Lin R, Tejada M, Frantz G, Peale F, Hillan K, et al. The endocrine-gland-derived VEGF homologue Bv8 promotes angiogenesis in the testis: Localization of Bv8 receptors to endothelial cells. Proc Natl Acad Sci U S A. 2003;100:2685-90 pubmed
    ..Here we describe the characterization of a highly related molecule, Bv8, also known as prokineticin-2. Human Bv8 shares 60% identity and 75% similarity with EG-VEGF...
  5. Zhang C, Ng K, Li J, He F, Anderson D, Sun Y, et al. Prokineticin 2 is a target gene of proneural basic helix-loop-helix factors for olfactory bulb neurogenesis. J Biol Chem. 2007;282:6917-21 pubmed
    b>Prokineticin 2, a cysteine-rich secreted protein, regulates diverse biological functions including the neurogenesis of olfactory bulb...
  6. Urayama K, Guilini C, Turkeri G, Takir S, Kurose H, Messaddeq N, et al. Prokineticin receptor-1 induces neovascularization and epicardial-derived progenitor cell differentiation. Arterioscler Thromb Vasc Biol. 2008;28:841-9 pubmed publisher
    ..This study provides a novel insight for possible therapeutic strategies aiming at restoring pluripotency of adult EPDCs to promote neovasculogenesis by induction of cardiomyocyte PKR1 signaling. ..
  7. Watson R, Lilley E, Panesar M, Bhalay G, Langridge S, Tian S, et al. Increased prokineticin 2 expression in gut inflammation: role in visceral pain and intestinal ion transport. Neurogastroenterol Motil. 2012;24:65-75, e12 pubmed publisher
    b>Prokineticin 2 (PROK2) is an inflammatory cytokine-like molecule expressed predominantly by macrophages and neutrophils infiltrating sites of tissue damage...
  8. Xiao L, Zhang C, Li X, Gong S, Hu R, Balasubramanian R, et al. Signaling role of prokineticin 2 on the estrous cycle of female mice. PLoS ONE. 2014;9:e90860 pubmed publisher
    The possible signaling role of prokineticin 2 (PK2) and its receptor, prokineticin receptor 2 (PKR2), on female reproduction was investigated...
  9. Jethwa P, I ANSON H, Warner A, Prosser H, Hastings M, Maywood E, et al. Loss of prokineticin receptor 2 signaling predisposes mice to torpor. Am J Physiol Regul Integr Comp Physiol. 2008;294:R1968-79 pubmed publisher
    The genes encoding prokineticin 2 polypeptide (Prok2) and its cognate receptor (Prokr2/Gpcr73l1) are widely expressed in both the suprachiasmatic nucleus and its hypothalamic targets, and this signaling pathway has been implicated in the ..
  10. Castelli M, Amodeo G, Negri L, Lattanzi R, Maftei D, Gotti C, et al. Antagonism of the Prokineticin System Prevents and Reverses Allodynia and Inflammation in a Mouse Model of Diabetes. PLoS ONE. 2016;11:e0146259 pubmed publisher
    ..The prokineticin system contributes to altered sensitivity in diabetic neuropathy and its inhibition blocked both allodynia and inflammatory events underlying disease. ..
  11. Kurosaka D, Noda K, Yoshida K, Furuya K, Ukichi T, Takahashi E, et al. Elevation of Bombina variegata peptide 8 in mice with collagen-induced arthritis. BMC Musculoskelet Disord. 2009;10:45 pubmed publisher
    Bombina variegate peptide 8 (Bv8) is a small protein secreted by frog skin. Recently it has been shown to contribute to tumor angiogenesis in mouse model...
  12. LeCouter J, Lin R, Frantz G, Zhang Z, Hillan K, Ferrara N. 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. Endocrinology. 2003;144:2606-16 pubmed
    ..We propose that mouse EG-VEGF, like human EG-VEGF, plays a role in regulating the phenotype and growth properties of endothelial cells within distinct capillary beds. ..
  13. Zhou Q, Cheng M. Prokineticin 2 and circadian clock output. FEBS J. 2005;272:5703-9 pubmed
    ..of prokineticins, a pair of newly discovered regulatory proteins, with focus on the circadian function of prokineticin 2 (PK2) and its potential role in sleep-wake regulation...
  14. Severini C, Lattanzi R, Maftei D, Marconi V, Ciotti M, Petrocchi Passeri P, et al. Bv8/prokineticin 2 is involved in Aβ-induced neurotoxicity. Sci Rep. 2015;5:15301 pubmed publisher
    Bv8/Prokineticin 2 (PROK2) is a bioactive peptide initially discovered as a regulator of gastrointestinal motility...
  15. Zhou W, Li J, Hu W, Cheng M, Zhou Q. Prokineticin 2 is involved in the thermoregulation and energy expenditure. Regul Pept. 2012;179:84-90 pubmed publisher
    ..Here, we provided evidence that the regulatory peptide prokineticin 2 (PK2) played an important role in such an adaptation...
  16. Lattanzi R, Maftei D, Marconi V, Florenzano F, Franchi S, Borsani E, et al. Prokineticin 2 upregulation in the peripheral nervous system has a major role in triggering and maintaining neuropathic pain in the chronic constriction injury model. Biomed Res Int. 2015;2015:301292 pubmed publisher
    The new chemokine Prokineticin 2 (PROK2) and its receptors (PKR1 and PKR2) have a role in inflammatory pain and immunomodulation...
  17. Zhou Q, Burton K, Neal M, Qiao Y, Kanthasamy A, Sun Y, et al. Differential arousal regulation by prokineticin 2 signaling in the nocturnal mouse and the diurnal monkey. Mol Brain. 2016;9:78 pubmed publisher
    ..Here we report that prokineticin 2, previously shown as a circadian clock output molecule, is expressed in the intrinsically photosensitive ..
  18. Maftei D, Marconi V, Florenzano F, Giancotti L, Castelli M, Moretti S, et al. Controlling the activation of the Bv8/prokineticin system reduces neuroinflammation and abolishes thermal and tactile hyperalgesia in neuropathic animals. Br J Pharmacol. 2014;171:4850-65 pubmed publisher
    Chemokines are involved in neuroinflammation and contribute to chronic pain processing. The new chemokine prokineticin 2 (PROK2) and its receptors (PKR1 and PKR2 ) have a role in inflammatory pain and immunomodulation...
  19. Jilek A, Engel E, Beier D, Lepperdinger G. Murine Bv8 gene maps near a synteny breakpoint of mouse chromosome 6 and human 3p21. Gene. 2000;256:189-95 pubmed
    The genomic structure of the murine Bv8 gene was determined in 129/SvJ mouse, and the chromosomal localization was identified. Bv8 has first been characterized from skin secretion of the yellow-bellied toad, Bombina variegata...
  20. Gardiner J, Bataveljic A, Patel N, Bewick G, Roy D, Campbell D, et al. Prokineticin 2 is a hypothalamic neuropeptide that potently inhibits food intake. Diabetes. 2010;59:397-406 pubmed publisher
    b>Prokineticin 2 (PK2) is a hypothalamic neuropeptide expressed in central nervous system areas known to be involved in food intake. We therefore hypothesized that PK2 plays a role in energy homeostasis...
  21. Li J, Hu W, Zhou Q. Disruption of the circadian output molecule prokineticin 2 results in anxiolytic and antidepressant-like effects in mice. Neuropsychopharmacology. 2009;34:367-73 pubmed publisher
    ..b>Prokineticin 2 (PK2) is a signaling molecule that is critical for transmitting the circadian rhythms from the SCN...
  22. Shojaei F, Singh M, Thompson J, Ferrara N. Role of Bv8 in neutrophil-dependent angiogenesis in a transgenic model of cancer progression. Proc Natl Acad Sci U S A. 2008;105:2640-5 pubmed publisher
    The secreted Bv8 protein has been recently characterized as a regulator of myeloid cell mobilization and a neutrophil-derived mediator of tumor angiogenesis in several xenografts, but its role in tumor progression in an endogenous ..
  23. Ngan E, Lee K, Sit F, Poon H, Chan J, Sham M, et al. Prokineticin-1 modulates proliferation and differentiation of enteric neural crest cells. Biochim Biophys Acta. 2007;1773:536-45 pubmed
    ..Taken together, it is the first report demonstrating that Prok-1 acts as a gut mucosa/mesenchyme-derived factor and maintains proliferation and differentiation of enteric NCCs. ..
  24. Warnecke M, Oster H, Revelli J, Alvarez Bolado G, Eichele G. Abnormal development of the locus coeruleus in Ear2(Nr2f6)-deficient mice impairs the functionality of the forebrain clock and affects nociception. Genes Dev. 2005;19:614-25 pubmed
    ..We propose that neurons in the dorsal division of LC contribute to the regulation of the forebrain clock, at least in part, through targeted release of noradrenaline into the cortical area. ..
  25. Long J, Garel S, Alvarez Dolado M, Yoshikawa K, Osumi N, Alvarez Buylla A, et al. Dlx-dependent and -independent regulation of olfactory bulb interneuron differentiation. J Neurosci. 2007;27:3230-43 pubmed
    ..the expression of ErbB4 (v-erb-a erythroblastic leukemia viral oncogene homolog 4), Robo2 (roundabout homolog 2), Slit1 (slit homolog 1), and PK2 (prokineticin 2), which have all been shown to play essential roles in this migration.
  26. He X, Shen C, Lu Q, Li J, Wei Y, He L, et al. Prokineticin 2 Plays a Pivotal Role in Psoriasis. EBioMedicine. 2016;13:248-261 pubmed publisher
    ..Here, a neuroendocrine peptide (prokineticin 2, PK2), is highly expressed in human and mouse psoriatic skins but no significant change in other autoimmune ..