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Gene Review

Mdk  -  midkine

Mus musculus

Synonyms: MK, Mek, Midkine, Mk, Retinoic acid-induced differentiation factor
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Disease relevance of Mdk


High impact information on Mdk

  • To find a new target to suppress neointima formation, we investigated the possible role of midkine (MK), a heparin-binding growth factor with neurotrophic and chemotactic activities, in neointima formation [5].
  • Soluble MK as well as that bound to the substratum induced migration of macrophages in vitro [5].
  • Leukocyte recruitment to the vascular walls after injury was markedly decreased in MK-deficient mice [5].
  • MK expression increased during neointima formation caused by intraluminal balloon injury of the rat carotid artery [5].
  • These findings establish the Mek/Erk pathway as the dominant pathway involved in conferring the cytoskeletal and junctional manifestations of the Ras-induced transformed phenotype [6].

Chemical compound and disease context of Mdk


Biological context of Mdk


Anatomical context of Mdk


Associations of Mdk with chemical compounds


Physical interactions of Mdk


Regulatory relationships of Mdk

  • TTF-1 regulates expression of MK in the lung [15].
  • Midkine activated both PI3-kinase and MAP kinases, the latter activation was blocked by a PI3-kinase inhibitor [21].
  • Recombinant mouse MK (10 ng/ml) induced the increased expression of macrophage inflammatory protein 2 (MIP-2) mRNA in TEpiCs [22].
  • A newly identified gene MK is transiently expressed in early stages of retinoic acid-induced differentiation of embryonal carcinoma cells (Kadomatsu, K., M. Tomomura, and T. Muramatsu, 1988. Biochem. Biophys. Res. Commun. 151:1312-1318) [8].

Other interactions of Mdk


Analytical, diagnostic and therapeutic context of Mdk

  • The weight of the liver 7 and 14 days after partial hepatectomy was significantly less in Mdk (-/-) mice than wild-type mice [14].
  • Our in situ hybridization results revealed a widespread expression of MK transcripts that was not always consistent with the distribution of MK protein in developing tissues [12].
  • Western blot analysis revealed the presence of MK in amniotic fluid and cerebrospinal fluid, in amounts of more than 1 microgram/ml, raising the possibility that MK delivered by these fluids participates in the regulation of organogenesis [23].
  • This MK-binding protein was purified by affinity chromatography on an MK-agarose column followed by SDS polyacrylamide gel electrophoresis [2].
  • MK cDNA probe reacts with two bands, a 4 kb one and a 3 kb one, upon Southern blot analysis of Hin dIII fragments of mouse genomic DNA: the midkine gene (Mdk) is on the 4 kb fragment [24].


  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. 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]
  3. The angiogenic factor midkine is aberrantly expressed in NF1-deficient Schwann cells and is a mitogen for neurofibroma-derived cells. Mashour, G.A., Ratner, N., Khan, G.A., Wang, H.L., Martuza, R.L., Kurtz, A. Oncogene (2001) [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. Neointima formation in a restenosis model is suppressed in midkine-deficient mice. Horiba, M., Kadomatsu, K., Nakamura, E., Muramatsu, H., Ikematsu, S., Sakuma, S., Hayashi, K., Yuzawa, Y., Matsuo, S., Kuzuya, M., Kaname, T., Hirai, M., Saito, H., Muramatsu, T. J. Clin. Invest. (2000) [Pubmed]
  6. Reversal of the Ras-induced transformed phenotype by HR12, a novel ras farnesylation inhibitor, is mediated by the Mek/Erk pathway. Reuveni, H., Geiger, T., Geiger, B., Levitzki, A. J. Cell Biol. (2000) [Pubmed]
  7. Growth factor midkine is involved in the pathogenesis of diabetic nephropathy. Kosugi, T., Yuzawa, Y., Sato, W., Kawai, H., Matsuo, S., Takei, Y., Muramatsu, T., Kadomatsu, K. Am. J. Pathol. (2006) [Pubmed]
  8. A retinoic acid responsive gene MK found in the teratocarcinoma system is expressed in spatially and temporally controlled manner during mouse embryogenesis. Kadomatsu, K., Huang, R.P., Suganuma, T., Murata, F., Muramatsu, T. J. Cell Biol. (1990) [Pubmed]
  9. Antisense oligodeoxynucleotide targeted to Midkine, a heparin-binding growth factor, suppresses tumorigenicity of mouse rectal carcinoma cells. Takei, Y., Kadomatsu, K., Matsuo, S., Itoh, H., Nakazawa, K., Kubota, S., Muramatsu, T. Cancer Res. (2001) [Pubmed]
  10. Heparin-binding neurotrophic factor (HBNF) and MK, members of a new family of homologous, developmentally regulated proteins. Kovesdi, I., Fairhurst, J.L., Kretschmer, P.J., Böhlen, P. Biochem. Biophys. Res. Commun. (1990) [Pubmed]
  11. Mapping the midkine family of developmentally regulated signaling molecules. Peichel, C.L., Scherer, S.W., Tsui, L.C., Beier, D.R., Vogt, T.F. Mamm. Genome (1993) [Pubmed]
  12. 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]
  13. Midkine binds to anaplastic lymphoma kinase (ALK) and acts as a growth factor for different cell types. Stoica, G.E., Kuo, A., Powers, C., Bowden, E.T., Sale, E.B., Riegel, A.T., Wellstein, A. J. Biol. Chem. (2002) [Pubmed]
  14. The role of midkine and pleiotrophin in liver regeneration. Ochiai, K., Muramatsu, H., Yamamoto, S., Ando, H., Muramatsu, T. Liver Int. (2004) [Pubmed]
  15. Thyroid transcription factor (TTF) -1 regulates the expression of midkine (MK) during lung morphogenesis. Reynolds, P.R., Mucenski, M.L., Whitsett, J.A. Dev. Dyn. (2003) [Pubmed]
  16. A heparin-binding growth factor, midkine, binds to a chondroitin sulfate proteoglycan, PG-M/versican. Zou, K., Muramatsu, H., Ikematsu, S., Sakuma, S., Salama, R.H., Shinomura, T., Kimata, K., Muramatsu, T. Eur. J. Biochem. (2000) [Pubmed]
  17. 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]
  18. Midkine is a potent regulator of the catecholamine biosynthesis pathway in mouse aorta. Ezquerra, L., Herradon, G., Nguyen, T., Silos-Santiago, I., Deuel, T.F. Life Sci. (2006) [Pubmed]
  19. 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]
  20. A splicing factor, Prp8: preferential localization in the testis and ovary in adult mice. Takahashi, A., Muramatsu, H., Takagi, S., Fujisawa, H., Miyake, Y., Muramatsu, T. J. Biochem. (2001) [Pubmed]
  21. Haptotactic migration induced by midkine. Involvement of protein-tyrosine phosphatase zeta. Mitogen-activated protein kinase, and phosphatidylinositol 3-kinase. Qi, M., Ikematsu, S., Maeda, N., Ichihara-Tanaka, K., Sakuma, S., Noda, M., Muramatsu, T., Kadomatsu, K. J. Biol. Chem. (2001) [Pubmed]
  22. Midkine expression in the course of nephrogenesis and its role in ischaemic reperfusion injury. Sato, W., Yuzawa, Y., Kadomatsu, K., Tayasu, T., Muramatsu, H., Muramatsu, T., Matsuo, S. Nephrol. Dial. Transplant. (2002) [Pubmed]
  23. Midkine (MK) expression in extraembryonic tissues, amniotic fluid, and cerebrospinal fluid during mouse embryogenesis. Obama, H., Tsutsui, J., Ozawa, M., Yoshida, H., Yoshida, Y., Osame, M., Muramatsu, T. J. Biochem. (1995) [Pubmed]
  24. The midkine (MK) family of growth/differentiation factors: structure of an MK-related sequence in a pseudogene and evolutionary relationships among members of the MK family. Obama, H., Matsubara, S., Guénet, J.L., Muramatsu, T. J. Biochem. (1994) [Pubmed]
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