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Gene Review

PROK2  -  prokineticin 2

Homo sapiens

Synonyms: BV8, HH4, KAL4, MIT1, PK2, ...
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Disease relevance of PROK2

  • Clonal expansion of CD8+ BV8 T lymphocytes in bone marrow characterizes thymoma-associated B lymphopenia [1].
  • The present phase I study was devised to determine the toxicity, pharmacokinetic profile, and targeting capability of PK2 [2].
  • There was no significant difference between guttate and chronic types of psoriasis in the percentage of circulating T-cell receptor BV2 or BV8-bearing T cells, responsive to streptococcal superantigens, indicating that T-cell clonal anergy was a mechanism underlying the hyporesponsiveness [3].

Psychiatry related information on PROK2


High impact information on PROK2

  • We propose that BV8 CD8(+) T cells may play a role in the pathogenesis of this immunodeficiency syndrome [1].
  • PURPOSE: Preclinical studies have shown good anticancer activity following targeting of a polymer bearing doxorubicin with galactosamine (PK2) to the liver [2].
  • The t1/2 for oral calcitriol was 38 +/- 14 h for PK1 and 30 +/- 4 h for PK2 (not significant (NS)) [5].
  • Functional studies showed that PK1, PK2, and PK2beta stimulate intracellular Ca(2+) responses in PKR1-expressing cells with similar potencies [6].
  • The relative abundance of RNAs based upon PCR signal intensity showed that VEGF and EG-VEGF were highly expressed, whereas expression of prokineticin-2 was low [7].

Biological context of PROK2

  • Given their sequence homology to MIT1, we have named these spider venom peptides the MIT-like atracotoxin (ACTX) family [8].
  • Therefore, while the MIT-like ACTX family appears to adopt the ancestral disulfide-directed beta-hairpin protein fold of MIT1, a motif believed to be shared by other AVIT family peptides, variations in the amino acid sequence and surface charge result in a loss of activity on prokineticin receptors [8].
  • Three isolates (TC354, PK1, and PK2) were biologically cloned and retained their SI or NSI phenotypes in MT-2 and primary T-cell lines [9].
  • In this study we report the pharmacokinetics and imaging determined in the first patient enrolled in a phase I clinical study of the poly[N-(2-hydroxypropyl)methacrylamide] copolymer bearing doxorubicin and galactosamine, known as PK2 [10].
  • KOH extraction PK2 was analyzed by determination of its monosaccharide composition, as well as by methylation analyses using GC-MS, mono- ((13)C, (1)H NMR) and bidimensional ((1)H (obs.), (13)C HMQC) spectroscopy, and controlled Smith degradations [11].

Anatomical context of PROK2


Associations of PROK2 with chemical compounds

  • EG-VEGF/PK1 and PK2 were weakly expressed in NPEC and EPN [15].
  • Two pharmacokinetic studies (PK1, PK2) were performed 10 days apart, during which the patients received calcitriol after each dialysis [5].
  • The ability of agents described as gastrointestinal prokinetics (prokineticin-2, [Nle(13)]-motilin, ghrelin), to modulate nerve-mediated contractions of mouse isolated stomach and colon was determined and compared with the prokinetic and 5-HT(4) receptor agonist, metoclopramide [16].
  • 2% KOH, each at 100 degrees C. The alkaline extract was obtained in much higher yield (31.5%) and submitted to a freeze-thawing treatment, giving rise to a precipitate (PK2) of a mixture of (1-->3),(1-->4)-alpha-glucan (1.2:1 ratio, nigeran) and a (1-->3)-beta-glucan (laminaran) [17].
  • KOH, and the resulting extracts submitted to the freeze-thawing treatment, giving rise to precipitates (PK2) of a mixture of alpha-glucan (nigeran) and beta-glucan, which were suspended in aqueous 0.5% NaOH at 50 degrees C, dissolving preferentially the beta-glucan [18].

Other interactions of PROK2

  • The mutations in PROK2 were detected in the heterozygous state, whereas PROKR2 mutations were found in the heterozygous, homozygous, or compound heterozygous state [19].

Analytical, diagnostic and therapeutic context of PROK2

  • Here, we report the molecular cloning and pharmacological characterization of an alternatively spliced product of the PK2 gene encoding 21 additional amino acids compared with PK2, designated PK2L (for PK2 long form) [6].
  • In AIH patients an accumulation of T cells expressing TCRBV 13S1, BV8 and BV5S3 was observed [20].


  1. Clonal expansion of CD8+ BV8 T lymphocytes in bone marrow characterizes thymoma-associated B lymphopenia. Masci, A.M., Palmieri, G., Vitiello, L., Montella, L., Perna, F., Orlandi, P., Abbate, G., Zappacosta, S., De Palma, R., Racioppi, L. Blood (2003) [Pubmed]
  2. Hepatic drug targeting: phase I evaluation of polymer-bound doxorubicin. Seymour, L.W., Ferry, D.R., Anderson, D., Hesslewood, S., Julyan, P.J., Poyner, R., Doran, J., Young, A.M., Burtles, S., Kerr, D.J. J. Clin. Oncol. (2002) [Pubmed]
  3. Hyporesponsiveness of peripheral blood lymphocytes to streptococcal superantigens in patients with guttate psoriasis: evidence for systemic stimulation of T cells with superantigens released from focally infecting Streptococcus pyogenes. Tokura, Y., Seo, N., Ohshima, A., Wakita, H., Yokote, R., Furukawa, F., Takigawa, M. Arch. Dermatol. Res. (1999) [Pubmed]
  4. Distinct localization of prokineticin 2 and prokineticin receptor 2 mRNAs in the rat suprachiasmatic nucleus. Masumoto, K.H., Nagano, M., Takashima, N., Hayasaka, N., Hiyama, H., Matsumoto, S., Inouye, S.T., Shigeyoshi, Y. Eur. J. Neurosci. (2006) [Pubmed]
  5. Pharmacokinetics and efficacy of pulse oral versus intravenous calcitriol in hemodialysis patients. Levine, B.S., Song, M. J. Am. Soc. Nephrol. (1996) [Pubmed]
  6. Identification and pharmacological characterization of prokineticin 2 beta as a selective ligand for prokineticin receptor 1. Chen, J., Kuei, C., Sutton, S., Wilson, S., Yu, J., Kamme, F., Mazur, C., Lovenberg, T., Liu, C. Mol. Pharmacol. (2005) [Pubmed]
  7. Localization and quantification of cyclic changes in the expression of endocrine gland vascular endothelial growth factor in the human corpus luteum. Fraser, H.M., Bell, J., Wilson, H., Taylor, P.D., Morgan, K., Anderson, R.A., Duncan, W.C. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
  8. Discovery of an MIT-like atracotoxin family: spider venom peptides that share sequence homology but not pharmacological properties with AVIT family proteins. Wen, S., Wilson, D.T., Kuruppu, S., Korsinczky, M.L., Hedrick, J., Pang, L., Szeto, T., Hodgson, W.C., Alewood, P.F., Nicholson, G.M. Peptides (2005) [Pubmed]
  9. Syncytium induction in primary CD4+ T-cell lines from normal donors by human immunodeficiency virus type 1 isolates with non-syncytium-inducing genotype and phenotype in MT-2 cells. Todd, B.J., Kedar, P., Pope, J.H. J. Virol. (1995) [Pubmed]
  10. Preliminary clinical study of the distribution of HPMA copolymers bearing doxorubicin and galactosamine. Julyan, P.J., Seymour, L.W., Ferry, D.R., Daryani, S., Boivin, C.M., Doran, J., David, M., Anderson, D., Christodoulou, C., Young, A.M., Hesslewood, S., Kerr, D.J. Journal of controlled release : official journal of the Controlled Release Society. (1999) [Pubmed]
  11. Structural characterization of a polysaccharide and a beta-glucan isolated from the edible mushroom Flammulina velutipes. Smiderle, F.R., Carbonero, E.R., Mellinger, C.G., Sassaki, G.L., Gorin, P.A., Iacomini, M. Phytochemistry (2006) [Pubmed]
  12. 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. Battersby, S., Critchley, H.O., Morgan, K., Millar, R.P., Jabbour, H.N. J. Clin. Endocrinol. Metab. (2004) [Pubmed]
  13. Prokineticin-1 modulates proliferation and differentiation of enteric neural crest cells. Ngan, E.S., Lee, K.Y., Sit, F.Y., Poon, H.C., Chan, J.K., Sham, M.H., Lui, V.C., Tam, P.K. Biochim. Biophys. Acta (2007) [Pubmed]
  14. T-cell hybridoma specific for myelin oligodendrocyte glycoprotein-35-55 peptide produced from HLA-DRB1*1501-transgenic mice. Chou, Y.K., Culbertson, N., Rich, C., LaTocha, D., Buenafe, A.C., Huan, J., Link, J., Wands, J.M., Born, W.K., Offner, H., Bourdette, D.N., Burrows, G.G., Vandenbark, A.A. J. Neurosci. Res. (2004) [Pubmed]
  15. 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. Pasquali, D., Rossi, V., Staibano, S., De Rosa, G., Chieffi, P., Prezioso, D., Mirone, V., Mascolo, M., Tramontano, D., Bellastella, A., Sinisi, A.A. Endocrinology (2006) [Pubmed]
  16. Prokineticin-2, motilin, ghrelin and metoclopramide: prokinetic utility in mouse stomach and colon. Bassil, A.K., Dass, N.B., Murray, C.D., Muir, A., Sanger, G.J. Eur. J. Pharmacol. (2005) [Pubmed]
  17. Elucidation of polysaccharide origin in Ramalina peruviana symbiosis. Cordeiro, L.M., Stocker-Wörgötter, E., Gorin, P.A., Iacomini, M. FEMS Microbiol. Lett. (2004) [Pubmed]
  18. Comparative studies of the polysaccharides from species of the genus Ramalina-lichenized fungi-of three distinct habitats. Cordeiro, L.M., Stocker-Wörgötter, E., Gorin, P.A., Iacomini, M. Phytochemistry (2003) [Pubmed]
  19. Kallmann syndrome: mutations in the genes encoding prokineticin-2 and prokineticin receptor-2. Dod??, C., Teixeira, L., Levilliers, J., Fouveaut, C., Bouchard, P., Kottler, M.L., Lespinasse, J., Lienhardt-Roussie, A., Mathieu, M., Moerman, A., Morgan, G., Murat, A., Toublanc, J.E., Wolczynski, S., Delpech, M., Petit, C., Young, J., Hardelin, J.P. PLoS Genet. (2006) [Pubmed]
  20. T cell receptor Vbeta chain restriction and preferred CDR3 motifs of liver-kidney microsomal antigen (LKM-1)-reactive T cells from autoimmune hepatitis patients. Arenz, M., Pingel, S., Schirmacher, P., Meyer zum Büschenfelde, K.H., Löhr, H.F. Liver (2001) [Pubmed]
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