Midkine

Midkine (neurite growth-promoting factor 2)
File:PBB Protein MDK image.jpg PDB rendering based on 1mkc.
Available structures PDB Ortholog search: Template:Homologene2PDBe PDBe, Template:Homologene2uniprot RCSB List of PDB id codes 1mkc​, 1mkn​
Identifiers
Symbols	MDK ; MK; FLJ27379; NEGF2
External IDs	Template:OMIM5 Template:MGI HomoloGene: 1792
Gene ontology Molecular function Template:GNF GO Template:GNF GO Template:GNF GO Cellular component Template:GNF GO Template:GNF GO Biological process Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO
RNA expression pattern
File:PBB GE MDK 209035 at tn.png
More reference expression data
Orthologs
Template:GNF Ortholog box
Species	Human	Mouse
Entrez	n/a	n/a
Ensembl	n/a	n/a
UniProt	n/a	n/a
RefSeq (mRNA)	n/a	n/a
RefSeq (protein)	n/a	n/a
Location (UCSC)	n/a	n/a
PubMed search	n/a	n/a

Midkine (MK, MDK), or Neurite Growth-promoting Factor 2, is a basic heparin-binding growth factor of low molecular weight, a member of the NEGF family founded by Pleiotrophin (NEGF1, 46% homologous with MK). It is a nonglycosylated protein, composed of two domains held by disulfide bridges. It is a developmentaly important retinoic acid-responsive gene product strongly induced during mid-gestation, hence the name midkine . Restricted mainly to certain tissues in the normal adult, it is strongly induced during oncogenesis, inflammation and tissue repair.

MK is pleiotropic, capable of exerting activities such as cell proliferation, cell migration, angiogenesis and fibrinolysis. A molecular complex containing receptor-type tyrosine phosphatase zeta (PTPζ), low density lipoprotein receptor-related protein (LRP), anaplastic leukemia kinase (ALK) and syndecans is considered to be its receptor.

Further reading

• Uehara K, Matsubara S, Kadomatsu K; et al. (1992). "Genomic structure of human midkine (MK), a retinoic acid-responsive growth/differentiation factor". J. Biochem. 111 (5): 563–7. PMID 1639750.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Wujek JR, Haleem-Smith H, Yamada Y; et al. (1991). "Evidence that the B2 chain of laminin is responsible for the neurite outgrowth-promoting activity of astrocyte extracellular matrix". Brain Res. Dev. Brain Res. 55 (2): 237–47. PMID 1701366.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Kretschmer PJ, Fairhurst JL, Decker MM; et al. (1992). "Cloning, characterization and developmental regulation of two members of a novel human gene family of neurite outgrowth-promoting proteins". Growth Factors. 5 (2): 99–114. PMID 1768439.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Shoyab M, McDonald VL, Dick K; et al. (1991). "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". Biochem. Biophys. Res. Commun. 179 (1): 572–8. PMID 1883381.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Tsutsui J, Uehara K, Kadomatsu K; et al. (1991). "A new family of heparin-binding factors: strong conservation of midkine (MK) sequences between the human and the mouse". Biochem. Biophys. Res. Commun. 176 (2): 792–7. PMID 2025291.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• O'Hara B, Jenkins NA, Gilbert DJ; et al. (1995). "Chromosomal assignment of the heparin-binding cytokine genes MDK and PTN in mouse and man". Cytogenet. Cell Genet. 69 (1–2): 40–3. PMID 7835084.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Kaname T, Kuwano A, Murano I; et al. (1993). "Midkine gene (MDK), a gene for prenatal differentiation and neuroregulation, maps to band 11p11.2 by fluorescence in situ hybridization". Genomics. 17 (2): 514–5. doi:10.1006/geno.1993.1359. PMID 8406506.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Fairhurst JL, Kretschmer PJ, Kovacs E; et al. (1993). "Structure of the gene coding for the human retinoic acid-inducible factor, MK". DNA Cell Biol. 12 (2): 139–47. PMID 8471163.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Kojima T, Katsumi A, Yamazaki T; et al. (1996). "Human ryudocan from endothelium-like cells binds basic fibroblast growth factor, midkine, and tissue factor pathway inhibitor". J. Biol. Chem. 271 (10): 5914–20. PMID 8621465.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Mahoney SA, Perry M, Seddon A; et al. (1996). "Transglutaminase forms midkine homodimers in cerebellar neurons and modulates the neurite-outgrowth response". Biochem. Biophys. Res. Commun. 224 (1): 147–52. doi:10.1006/bbrc.1996.0998. PMID 8694802.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Nakanishi T, Kadomatsu K, Okamoto T; et al. (1997). "Expression of syndecan-1 and -3 during embryogenesis of the central nervous system in relation to binding with midkine". J. Biochem. 121 (2): 197–205. PMID 9089390.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Iwasaki W, Nagata K, Hatanaka H; et al. (1998). "Solution structure of midkine, a new heparin-binding growth factor". EMBO J. 16 (23): 6936–46. doi:10.1093/emboj/16.23.6936. PMID 9384573.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Ratovitski EA, Kotzbauer PT, Milbrandt J; et al. (1998). "Midkine induces tumor cell proliferation and binds to a high affinity signaling receptor associated with JAK tyrosine kinases". J. Biol. Chem. 273 (6): 3654–60. PMID 9452495.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Maeda N, Ichihara-Tanaka K, Kimura T; et al. (1999). "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". J. Biol. Chem. 274 (18): 12474–9. PMID 10212223.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Meng K, Rodriguez-Peña A, Dimitrov T; et al. (2000). "Pleiotrophin signals increased tyrosine phosphorylation of beta beta-catenin through inactivation of the intrinsic catalytic activity of the receptor-type protein tyrosine phosphatase beta/zeta". Proc. Natl. Acad. Sci. U.S.A. 97 (6): 2603–8. doi:10.1073/pnas.020487997. PMID 10706604.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Muramatsu H, Zou K, Sakaguchi N; et al. (2000). "LDL receptor-related protein as a component of the midkine receptor". Biochem. Biophys. Res. Commun. 270 (3): 936–41. doi:10.1006/bbrc.2000.2549. PMID 10772929.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Kato M, Maeta H, Kato S; et al. (2001). "Immunohistochemical and in situ hybridization analyses of midkine expression in thyroid papillary carcinoma". Mod. Pathol. 13 (10): 1060–5. doi:10.1038/modpathol.3880195. PMID 11048798.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Hayashi K, Kadomatsu K, Muramatsu T (2002). "Requirement of chondroitin sulfate/dermatan sulfate recognition in midkine-dependent migration of macrophages". Glycoconj. J. 18 (5): 401–6. PMID 11925507.CS1 maint: Multiple names: authors list (link)
• Sumi Y, Muramatsu H, Takei Y; et al. (2002). "Midkine, a heparin-binding growth factor, promotes growth and glycosaminoglycan synthesis of endothelial cells through its action on smooth muscle cells in an artificial blood vessel model". J. Cell. Sci. 115 (Pt 13): 2659–67. PMID 12077357.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Stoica GE, Kuo A, Powers C; et al. (2002). "Midkine binds to anaplastic lymphoma kinase (ALK) and acts as a growth factor for different cell types". J. Biol. Chem. 277 (39): 35990–8. doi:10.1074/jbc.M205749200. PMID 12122009.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)