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Gene Review

Ptn  -  pleiotrophin

Mus musculus

Synonyms: HARP, HB-GAM, HBBM, HBBN, HBGF-8, ...
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Disease relevance of Ptn


High impact information on Ptn


Chemical compound and disease context of Ptn


Biological context of Ptn


Anatomical context of Ptn


Associations of Ptn with chemical compounds

  • These results suggest that syndecans are expressed primarily in reactive astrocytes, and may provide a supportive environment for regenerating axons in concert with heparin-binding growth factors (e.g., FGF and PTN) in the injured brain [18].
  • Surprisingly, the anti-apoptotic effect of PTN was completely blocked by the MAP kinase inhibitor UO126, but was not affected by the PI 3-kinase inhibitor LY294002 [19].
  • In vivo treatment with PTN (20 ng/g) increased bromodeoxyuridine incorporation (by 2.24-fold) and PCNA expression (by 1.71-fold) during day 7 to day 14, indicating that PTN induces cell proliferation in mouse heart [20].
  • Heparin-binding growth factor, pleiotrophin, mediates neuritogenic activity of embryonic pig brain-derived chondroitin sulfate/dermatan sulfate hybrid chains [21].
  • Oversulfated disaccharides and nonconsecutive iduronic acid-containing units were the requirements for the E-CS/DS chains to bind PTN and to exhibit the neuritogenic activities [21].

Physical interactions of Ptn

  • These findings supported the hypothesis that parts of the MK and HB-GAM are translocated to the nucleus after binding with nucleolin [22].
  • Midkine is a 13-kDa heparin-binding growth factor with 45% sequence identity to pleiotrophin [23].
  • Pleiotrophin has been demonstrated to bind to protein-tyrosine phosphatase zeta (PTPzeta) with high affinity [23].
  • This competition may result in the presentation of perlecan-bound growth factors such as HB-GAM to effect synaptic induction [24].

Regulatory relationships of Ptn


Other interactions of Ptn

  • The level of MK protein decreased considerably in the 16.5 dpc embryo, whereas HB-GAM staining persisted in many tissues [14].
  • In our model, FGF receptor1 (FGFR1) and PTN mRNA levels were upregulated in reactive astrocytes [18].
  • The involvement of the core protein was also shown in the binding of MK and PTN to syndecan-1, suggesting the possibility of cooperation with the HS and/or CS chains in the binding of these growth factors and their delivery to the cell surface receptors [28].
  • These results suggested that PTPzeta is a common receptor for midkine and pleiotrophin [23].
  • Further, our in vitro studies show that exogenously added HB-GAM inhibits formation and growth of FGF-2, but not EGF, stimulated neurospheres, restricts the number of nestin-positive neural stem cells, and inhibits FGF receptor phosphorylation [29].

Analytical, diagnostic and therapeutic context of Ptn

  • In a subcutaneous tumor xenograft mouse model, in vivo growth is markedly reduced upon PTN depletion, which is paralleled by decreased PTN serum levels [2].
  • CONCLUSIONS: MK and PTN are involved both in the inflammatory and reparative processes after partial hepatectomy, and as a whole are beneficial for liver regeneration [30].
  • A 15.3-kDa protein detected only in the conditioned medium of neural stem cells was determined as pleiotrophin (PTN) by SELDI-TOF-MS and ProteinChip-tandem MS systems [31].
  • Overexpression of Ptn by in vitro electroporation of P0 rat retinal explants partially blocks rod differentiation and promotes bipolar cell production, similar to effects of exogenous CNTF and leukemia inhibitory factor (LIF) [25].
  • An unusual effect of PTN (50 ng/ml) was the induction of type I collagen synthesis by chondrocytes in organ cultures of chick nasal cartilage and rat growth plates [32].


  1. Differential expression of pleiotrophin and midkine in advanced neuroblastomas. Nakagawara, A., Milbrandt, J., Muramatsu, T., Deuel, T.F., Zhao, H., Cnaan, A., Brodeur, G.M. Cancer Res. (1995) [Pubmed]
  2. Ribozyme-targeting reveals the rate-limiting role of pleiotrophin in glioblastoma. Grzelinski, M., Bader, N., Czubayko, F., Aigner, A. Int. J. Cancer (2005) [Pubmed]
  3. Involvement of heparin affin regulatory peptide in human prostate cancer. Vacherot, F., Caruelle, D., Chopin, D., Gil-Diez, S., Barritault, D., Caruelle, J.P., Courty, J. Prostate (1999) [Pubmed]
  4. Female infertility in mice deficient in midkine and pleiotrophin, which form a distinct family of growth factors. Muramatsu, H., Zou, P., Kurosawa, N., Ichihara-Tanaka, K., Maruyama, K., Inoh, K., Sakai, T., Chen, L., Sato, M., Muramatsu, T. Genes Cells (2006) [Pubmed]
  5. Ribozyme-targeting elucidates a direct role of pleiotrophin in tumor growth. Czubayko, F., Riegel, A.T., Wellstein, A. J. Biol. Chem. (1994) [Pubmed]
  6. Relationship between serum concentrations of the growth factor pleiotrophin and pleiotrophin-positive tumors. Souttou, B., Juhl, H., Hackenbruck, J., Röckseisen, M., Klomp, H.J., Raulais, D., Vigny, M., Wellstein, A. J. Natl. Cancer Inst. (1998) [Pubmed]
  7. N-syndecan deficiency impairs neural migration in brain. Hienola, A., Tumova, S., Kulesskiy, E., Rauvala, H. J. Cell Biol. (2006) [Pubmed]
  8. A dominant-negative pleiotrophin mutant introduced by homologous recombination leads to germ-cell apoptosis in male mice. Zhang, N., Yeh, H.J., Zhong, R., Li, Y.S., Deuel, T.F. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  9. Dominant negative effectors of heparin affin regulatory peptide (HARP) angiogenic and transforming activities. Bernard-Pierrot, I., Delbé, J., Rouet, V., Vigny, M., Kerros, M.E., Caruelle, D., Raulais, D., Barritault, D., Courty, J., Milhiet, P.E. J. Biol. Chem. (2002) [Pubmed]
  10. Ribozyme targeting of the growth factor pleiotrophin in established tumors: a gene therapy approach. Malerczyk, C., Schulte, A.M., Czubayko, F., Bellon, L., Macejak, D., Riegel, A.T., Wellstein, A. Gene Ther. (2005) [Pubmed]
  11. Cell density-dependent expression of heparin-binding growth-associated molecule (HB-GAM, p18) and its down-regulation by fibroblast growth factors. Merenmies, J. FEBS Lett. (1992) [Pubmed]
  12. Protein tyrosine phosphatase receptor type Z is involved in hippocampus-dependent memory formation through dephosphorylation at Y1105 on p190 RhoGAP. Tamura, H., Fukada, M., Fujikawa, A., Noda, M. Neurosci. Lett. (2006) [Pubmed]
  13. Midkine regulates pleiotrophin organ-specific gene expression: evidence for transcriptional regulation and functional redundancy within the pleiotrophin/midkine developmental gene family. Herradon, G., Ezquerra, L., Nguyen, T., Silos-Santiago, I., Deuel, T.F. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  14. Expression of the heparin-binding cytokines, midkine (MK) and HB-GAM (pleiotrophin) is associated with epithelial-mesenchymal interactions during fetal development and organogenesis. Mitsiadis, T.A., Salmivirta, M., Muramatsu, T., Muramatsu, H., Rauvala, H., Lehtonen, E., Jalkanen, M., Thesleff, I. Development (1995) [Pubmed]
  15. Midkine, a newly discovered regulator of the renin-angiotensin pathway in mouse aorta: significance of the pleiotrophin/midkine developmental gene family in angiotensin II signaling. Ezquerra, L., Herradon, G., Nguyen, T., Silos-Santiago, I., Deuel, T.F. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  16. Genomic organization of the mouse OSF-1 gene. Katoh, K., Takeshita, S., Sato, M., Ito, T., Amann, E. DNA Cell Biol. (1992) [Pubmed]
  17. A role of midkine in the development of the neuromuscular junction. Zhou, H., Muramatsu, T., Halfter, W., Tsim, K.W., Peng, H.B. Mol. Cell. Neurosci. (1997) [Pubmed]
  18. Increased syndecan expression by pleiotrophin and FGF receptor-expressing astrocytes in injured brain tissue. Iseki, K., Hagino, S., Mori, T., Zhang, Y., Yokoya, S., Takaki, H., Tase, C., Murakawa, M., Wanaka, A. Glia (2002) [Pubmed]
  19. Anti-apoptotic signaling of pleiotrophin through its receptor, anaplastic lymphoma kinase. Bowden, E.T., Stoica, G.E., Wellstein, A. J. Biol. Chem. (2002) [Pubmed]
  20. Dynamic changes of gene expression profiles during postnatal development of the heart in mice. Chen, H.W., Yu, S.L., Chen, W.J., Yang, P.C., Chien, C.T., Chou, H.Y., Li, H.N., Peck, K., Huang, C.H., Lin, F.Y., Chen, J.J., Lee, Y.T. Heart (2004) [Pubmed]
  21. Heparin-binding growth factor, pleiotrophin, mediates neuritogenic activity of embryonic pig brain-derived chondroitin sulfate/dermatan sulfate hybrid chains. Bao, X., Mikami, T., Yamada, S., Faissner, A., Muramatsu, T., Sugahara, K. J. Biol. Chem. (2005) [Pubmed]
  22. Identification of nucleolin as a binding protein for midkine (MK) and heparin-binding growth associated molecule (HB-GAM). Take, M., Tsutsui, J., Obama, H., Ozawa, M., Nakayama, T., Maruyama, I., Arima, T., Muramatsu, T. J. Biochem. (1994) [Pubmed]
  23. A receptor-like protein-tyrosine phosphatase PTPzeta/RPTPbeta binds a heparin-binding growth factor midkine. Involvement of arginine 78 of midkine in the high affinity binding to PTPzeta. Maeda, N., Ichihara-Tanaka, K., Kimura, T., Kadomatsu, K., Muramatsu, T., Noda, M. J. Biol. Chem. (1999) [Pubmed]
  24. The relationship between perlecan and dystroglycan and its implication in the formation of the neuromuscular junction. Peng, H.B., Ali, A.A., Daggett, D.F., Rauvala, H., Hassell, J.R., Smalheiser, N.R. Cell Adhes. Commun. (1998) [Pubmed]
  25. Involvement of Pleiotrophin in CNTF-mediated differentiation of the late retinal progenitor cells. Roger, J., Brajeul, V., Thomasseau, S., Hienola, A., Sahel, J.A., Guillonneau, X., Goureau, O. Dev. Biol. (2006) [Pubmed]
  26. Pleiotrophin mRNA is highly expressed in neural stem (progenitor) cells of mouse ventral mesencephalon and the product promotes production of dopaminergic neurons from embryonic stem cell-derived nestin-positive cells. Jung, C.G., Hida, H., Nakahira, K., Ikenaka, K., Kim, H.J., Nishino, H. FASEB J. (2004) [Pubmed]
  27. Enhanced hippocampal GABAergic inhibition in mice overexpressing heparin-binding growth-associated molecule. Pavlov, I., Rauvala, H., Taira, T. Neuroscience (2006) [Pubmed]
  28. Chondroitin sulfate chains on syndecan-1 and syndecan-4 from normal murine mammary gland epithelial cells are structurally and functionally distinct and cooperate with heparan sulfate chains to bind growth factors. A novel function to control binding of midkine, pleiotrophin, and basic fibroblast growth factor. Deepa, S.S., Yamada, S., Zako, M., Goldberger, O., Sugahara, K. J. Biol. Chem. (2004) [Pubmed]
  29. HB-GAM inhibits proliferation and enhances differentiation of neural stem cells. Hienola, A., Pekkanen, M., Raulo, E., Vanttola, P., Rauvala, H. Mol. Cell. Neurosci. (2004) [Pubmed]
  30. The role of midkine and pleiotrophin in liver regeneration. Ochiai, K., Muramatsu, H., Yamamoto, S., Ando, H., Muramatsu, T. Liver Int. (2004) [Pubmed]
  31. Identification of pleiotrophin in conditioned medium secreted from neural stem cells by SELDI-TOF and SELDI-tandem mass spectrometry. Furuta, M., Shiraishi, T., Okamoto, H., Mineta, T., Tabuchi, K., Shiwa, M. Brain Res. Dev. Brain Res. (2004) [Pubmed]
  32. Pleiotrophin/Osteoblast-stimulating factor 1: dissecting its diverse functions in bone formation. Tare, R.S., Oreffo, R.O., Clarke, N.M., Roach, H.I. J. Bone Miner. Res. (2002) [Pubmed]
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