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Gene Review

MDK  -  midkine (neurite growth-promoting factor 2)

Homo sapiens

Synonyms: ARAP, Amphiregulin-associated protein, FLJ27379, MK, MK1, ...
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Disease relevance of MDK


Psychiatry related information on MDK


High impact information on MDK


Chemical compound and disease context of MDK


Biological context of MDK


Anatomical context of MDK


Associations of MDK with chemical compounds

  • Midkine (MK) is a heparin-binding growth factor with migration-promoting and survival-promoting activities [16].
  • The specific binding of MK to cells is independent of heparan sulfate and chondroitin sulfate expression [1].
  • METHODS: The mitogenic activity of MK on cultured endometriotic stromal cells was examined by measuring 5-bromo-2'-deoxyuridine (BrdU) incorporation [4].
  • MK-induced migration of peritoneal exudate macrophages was inhibited by heparin, chondroitin sulfate E and dermatan sulfate, but not by chondroitin sulfate D or chondroitin 6-sulfate [17].
  • 3) Gln42 or Gln44 in the N-terminal half and Gln95 in the C-terminal half served as amine acceptors in the cross-linking reaction, as judged from the incorporation of putrescine into whole MK or each half domain, and the competitive inhibition of the cross-linking by MK-derived peptides containing Gln residue(s) [18].

Physical interactions of MDK


Regulatory relationships of MDK


Other interactions of MDK

  • The dissociation constant of binding between LRP and MK was 3.5 nM [16].
  • Our results suggest that the cell surface-expressed nucleolin serves as a low affinity receptor for MK and could be implicated in its entry process [1].
  • Stem cell factor and MK concentrations above a defined threshold in serum of NF1 patients are of diagnostic benefit for 96% of patients in the cohort tested [15].
  • The apparent dissociation constants for purified ryudocan were as follows: bFGF, 0.50 nM; MK, 0.30 nM; and TFPI, 0.74 nM [21].
  • Within the NF1 group, MK levels increased dramatically at puberty from an average of 0.79 ng/mL in patients <18 years to 1.18 ng/mL in patients >18 years old [15].

Analytical, diagnostic and therapeutic context of MDK


  1. The anti-HIV cytokine midkine binds the cell surface-expressed nucleolin as a low affinity receptor. Said, E.A., Krust, B., Nisole, S., Svab, J., Briand, J.P., Hovanessian, A.G. J. Biol. Chem. (2002) [Pubmed]
  2. Midkine promoter can mediate transcriptional activation of a fused suicide gene in a broader range of human breast cancer compared with c-erbB-2 promoter. Yu, L., Yamamoto, N., Kadomatsu, K., Muramatsu, T., Matsubara, S., Sakiyama, S., Tagawa, M. Oncology (2004) [Pubmed]
  3. Amphiregulin-associated protein: complete amino acid sequence of a protein produced by the 12-0-tetradecanoylphorbol-13-acetate-treated human breast adenocarcinoma cell line MCF-7. Shoyab, M., McDonald, V.L., Dick, K., Modrell, B., Malik, N., Plowman, G.D. Biochem. Biophys. Res. Commun. (1991) [Pubmed]
  4. Possible implication of midkine in the development of endometriosis. Hirota, Y., Osuga, Y., Koga, K., Yoshino, O., Hirata, T., Harada, M., Morimoto, C., Yano, T., Tsutsumi, O., Sakuma, S., Muramatsu, T., Taketani, Y. Hum. Reprod. (2005) [Pubmed]
  5. Midkine and pleiotrophin in neural development and cancer. Kadomatsu, K., Muramatsu, T. Cancer Lett. (2004) [Pubmed]
  6. Solution structure of midkine, a new heparin-binding growth factor. Iwasaki, W., Nagata, K., Hatanaka, H., Inui, T., Kimura, T., Muramatsu, T., Yoshida, K., Tasumi, M., Inagaki, F. EMBO J. (1997) [Pubmed]
  7. Juvenile hormone receptors in insect larval epidermis: identification by photoaffinity labeling. Palli, S.R., Osir, E.O., Eng, W., Boehm, M.F., Edwards, M., Kulcsar, P., Ujvary, I., Hiruma, K., Prestwich, G.D., Riddiford, L.M. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  8. A heparin sulfate-regulated human keratinocyte autocrine factor is similar or identical to amphiregulin. Cook, P.W., Mattox, P.A., Keeble, W.W., Pittelkow, M.R., Plowman, G.D., Shoyab, M., Adelman, J.P., Shipley, G.D. Mol. Cell. Biol. (1991) [Pubmed]
  9. Inhibition of HIV infection by the cytokine midkine. Callebaut, C., Nisole, S., Briand, J.P., Krust, B., Hovanessian, A.G. Virology (2001) [Pubmed]
  10. Chondroitin sulfate of appican, the proteoglycan form of amyloid precursor protein, produced by C6 glioma cells interacts with heparin-binding neuroregulatory factors. Umehara, Y., Yamada, S., Nishimura, S., Shioi, J., Robakis, N.K., Sugahara, K. FEBS Lett. (2004) [Pubmed]
  11. Glypican-2 binds to midkine: the role of glypican-2 in neuronal cell adhesion and neurite outgrowth. Kurosawa, N., Chen, G.Y., Kadomatsu, K., Ikematsu, S., Sakuma, S., Muramatsu, T. Glycoconj. J. (2001) [Pubmed]
  12. Identification of genes with differential expression in acquired drug-resistant gastric cancer cells using high-density oligonucleotide microarrays. Kang, H.C., Kim, I.J., Park, J.H., Shin, Y., Ku, J.L., Jung, M.S., Yoo, B.C., Kim, H.K., Park, J.G. Clin. Cancer Res. (2004) [Pubmed]
  13. Midkine gene (MDK), a gene for prenatal differentiation and neuroregulation, maps to band 11p11.2 by fluorescence in situ hybridization. Kaname, T., Kuwano, A., Murano, I., Uehara, K., Muramatsu, T., Kajii, T. Genomics (1993) [Pubmed]
  14. Structural and functional characterization of full-length heparin-binding growth associated molecule. Hampton, B.S., Marshak, D.R., Burgess, W.H. Mol. Biol. Cell (1992) [Pubmed]
  15. Circulating growth factor levels are associated with tumorigenesis in neurofibromatosis type 1. Mashour, G.A., Driever, P.H., Hartmann, M., Drissel, S.N., Zhang, T., Scharf, B., Felderhoff-Müser, U., Sakuma, S., Friedrich, R.E., Martuza, R.L., Mautner, V.F., Kurtz, A. Clin. Cancer Res. (2004) [Pubmed]
  16. LDL receptor-related protein as a component of the midkine receptor. Muramatsu, H., Zou, K., Sakaguchi, N., Ikematsu, S., Sakuma, S., Muramatsu, T. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  17. Requirement of chondroitin sulfate/dermatan sulfate recognition in midkine-dependent migration of macrophages. Hayashi, K., Kadomatsu, K., Muramatsu, T. Glycoconj. J. (2001) [Pubmed]
  18. Dimerization of midkine by tissue transglutaminase and its functional implication. Kojima, S., Inui, T., Muramatsu, H., Suzuki, Y., Kadomatsu, K., Yoshizawa, M., Hirose, S., Kimura, T., Sakakibara, S., Muramatsu, T. J. Biol. Chem. (1997) [Pubmed]
  19. Alteration of midkine expression in the ischemic brain of humans. Wada, M., Kamata, M., Aizu, Y., Morita, T., Hu, J., Oyanagi, K. J. Neurol. Sci. (2002) [Pubmed]
  20. Reciprocal expression of pleiotrophin and midkine in normal versus malignant lung tissues. Garver, R.I., Chan, C.S., Milner, P.G. Am. J. Respir. Cell Mol. Biol. (1993) [Pubmed]
  21. Human ryudocan from endothelium-like cells binds basic fibroblast growth factor, midkine, and tissue factor pathway inhibitor. Kojima, T., Katsumi, A., Yamazaki, T., Muramatsu, T., Nagasaka, T., Ohsumi, K., Saito, H. J. Biol. Chem. (1996) [Pubmed]
  22. Cloning, characterization and developmental regulation of two members of a novel human gene family of neurite outgrowth-promoting proteins. Kretschmer, P.J., Fairhurst, J.L., Decker, M.M., Chan, C.P., Gluzman, Y., Böhlen, P., Kovesdi, I. Growth Factors (1991) [Pubmed]
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