Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Biol Chem
2010 May 21;28521:16105-15. doi: 10.1074/jbc.M109.081232.
Show Gene links
Show Anatomy links
Midkine and pleiotrophin have bactericidal properties: preserved antibacterial activity in a family of heparin-binding growth factors during evolution.
Svensson SL
,
Pasupuleti M
,
Walse B
,
Malmsten M
,
Mörgelin M
,
Sjögren C
,
Olin AI
,
Collin M
,
Schmidtchen A
,
Palmer R
,
Egesten A
.
???displayArticle.abstract???
Antibacterial peptides of the innate immune system combat pathogenic microbes, but often have additional roles in promoting inflammation and as growth factors during tissue repair. Midkine (MK) and pleiotrophin (PTN) are the only two members of a family of heparin-binding growth factors. They show restricted expression during embryogenesis and are up-regulated in neoplasia. In addition, MK shows constitutive and inflammation-dependent expression in some non-transformed tissues of the adult. In the present study, we show that both MK and PTN display strong antibacterial activity, present at physiological salt concentrations. Electron microscopy of bacteria and experiments using artificial lipid bilayers suggest that MK and PTN exert their antibacterial action via a membrane disruption mechanism. The predicted structure of PTN, employing the previously solved MK structure as a template, indicates that both molecules consist of two domains, each containing three antiparallel beta-sheets. The antibacterial activity was mapped to the unordered C-terminal tails of both molecules and the last beta-sheets of the N-terminals. Analysis of the highly conserved MK and PTN orthologues from the amphibian Xenopus laevis and the fish Danio rerio suggests that they also harbor antibacterial activity in the corresponding domains. In support of an evolutionary conserved function it was found that the more distant orthologue, insect Miple2 from Drosophila melanogaster, also displays strong antibacterial activity. Taken together, the findings suggest that MK and PTN, in addition to their earlier described activities, may have previously unrealized important roles as innate antibiotics.
Altschul,
Gapped BLAST and PSI-BLAST: a new generation of protein database search programs.
1997, Pubmed
Altschul,
Gapped BLAST and PSI-BLAST: a new generation of protein database search programs.
1997,
Pubmed
Andersson,
Antimicrobial activities of heparin-binding peptides.
2004,
Pubmed
Aps,
Review: The physiology of saliva and transfer of drugs into saliva.
2005,
Pubmed
Bai,
Structure-dependent charge density as a determinant of antimicrobial activity of peptide analogues of defensin.
2009,
Pubmed
Bendtsen,
Improved prediction of signal peptides: SignalP 3.0.
2004,
Pubmed
Bengtson,
Activation of TAFI on the surface of Streptococcus pyogenes evokes inflammatory reactions by modulating the kallikrein/kinin system.
2009,
Pubmed
Brogden,
Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria?
2005,
Pubmed
Cole,
Cutting edge: IFN-inducible ELR- CXC chemokines display defensin-like antimicrobial activity.
2001,
Pubmed
De Yang,
LL-37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells.
2000,
Pubmed
Deuel,
Pleiotrophin: a cytokine with diverse functions and a novel signaling pathway.
2002,
Pubmed
Elsbach,
What is the real role of antimicrobial polypeptides that can mediate several other inflammatory responses?
2003,
Pubmed
Englund,
Miple1 and miple2 encode a family of MK/PTN homologues in Drosophila melanogaster.
2006,
Pubmed
Fabri,
Structural characterisation of native and recombinant forms of the neurotrophic cytokine MK.
1993,
Pubmed
Ganz,
Defensins: antimicrobial peptides of innate immunity.
2003,
Pubmed
Gijsbers,
GCP-2/CXCL6 synergizes with other endothelial cell-derived chemokines in neutrophil mobilization and is associated with angiogenesis in gastrointestinal tumors.
2005,
Pubmed
Henikoff,
Amino acid substitution matrices from protein blocks.
1992,
Pubmed
Hoover,
The structure of human macrophage inflammatory protein-3alpha /CCL20. Linking antimicrobial and CC chemokine receptor-6-binding activities with human beta-defensins.
2002,
Pubmed
Hoover,
The structure of human beta-defensin-1: new insights into structural properties of beta-defensins.
2001,
Pubmed
Iwasaki,
Solution structure of midkine, a new heparin-binding growth factor.
1997,
Pubmed
Kadomatsu,
cDNA cloning and sequencing of a new gene intensely expressed in early differentiation stages of embryonal carcinoma cells and in mid-gestation period of mouse embryogenesis.
1988,
Pubmed
Keates,
Macrophage-inflammatory protein-3alpha mediates epidermal growth factor receptor transactivation and ERK1/2 MAPK signaling in Caco-2 colonic epithelial cells via metalloproteinase-dependent release of amphiregulin.
2007,
Pubmed
Kilpelainen,
Heparin-binding growth-associated molecule contains two heparin-binding beta -sheet domains that are homologous to the thrombospondin type I repeat.
2000,
Pubmed
Koczulla,
An angiogenic role for the human peptide antibiotic LL-37/hCAP-18.
2003,
Pubmed
Kojima,
Synthetic peptides derived from midkine enhance plasminogen activator activity in bovine aortic endothelial cells.
1995,
Pubmed
Krishnakumari,
Interaction of antibacterial peptides spanning the carboxy-terminal region of human beta-defensins 1-3 with phospholipids at the air-water interface and inner membrane of E. coli.
2008,
Pubmed
Krzystek-Korpacka,
Circulating midkine in Crohn's disease: clinical implications.
2010,
Pubmed
Lai,
AMPed up immunity: how antimicrobial peptides have multiple roles in immune defense.
2009,
Pubmed
Larkin,
Clustal W and Clustal X version 2.0.
2007,
Pubmed
Lehrer,
Ultrasensitive assays for endogenous antimicrobial polypeptides.
1991,
Pubmed
Li,
Cloning and expression of a developmentally regulated protein that induces mitogenic and neurite outgrowth activity.
1990,
Pubmed
Linge,
The human CXC chemokine granulocyte chemotactic protein 2 (GCP-2)/CXCL6 possesses membrane-disrupting properties and is antibacterial.
2008,
Pubmed
Lucas,
Serum levels of Midkine in children and adolescents without malignant disease.
2010,
Pubmed
Malmsten,
Antimicrobial peptides derived from growth factors.
2007,
Pubmed
Maruyama,
Midkine, a heparin-binding growth factor, is fundamentally involved in the pathogenesis of rheumatoid arthritis.
2004,
Pubmed
Milner,
A novel 17 kD heparin-binding growth factor (HBGF-8) in bovine uterus: purification and N-terminal amino acid sequence.
1989,
Pubmed
Muramatsu,
Midkine and pleiotrophin: two related proteins involved in development, survival, inflammation and tumorigenesis.
2002,
Pubmed
Muramatsu,
alpha4beta1- and alpha6beta1-integrins are functional receptors for midkine, a heparin-binding growth factor.
2004,
Pubmed
Murphy,
Defensins are mitogenic for epithelial cells and fibroblasts.
1993,
Pubmed
Niyonsaba,
Antimicrobial peptides human beta-defensins stimulate epidermal keratinocyte migration, proliferation and production of proinflammatory cytokines and chemokines.
2007,
Pubmed
Palmer,
Anaplastic lymphoma kinase: signalling in development and disease.
2009,
Pubmed
Poirot,
3DCoffee@igs: a web server for combining sequences and structures into a multiple sequence alignment.
2004,
Pubmed
Raulo,
The two thrombospondin type I repeat domains of the heparin-binding growth-associated molecule bind to heparin/heparan sulfate and regulate neurite extension and plasticity in hippocampal neurons.
2005,
Pubmed
Rauvala,
An 18-kd heparin-binding protein of developing brain that is distinct from fibroblast growth factors.
1989,
Pubmed
Riddles,
Reassessment of Ellman's reagent.
1983,
Pubmed
Saitou,
The neighbor-joining method: a new method for reconstructing phylogenetic trees.
1987,
Pubmed
Schibli,
The solution structures of the human beta-defensins lead to a better understanding of the potent bactericidal activity of HBD3 against Staphylococcus aureus.
2002,
Pubmed
Sekiguchi,
Restricted expression of Xenopus midkine gene during early development.
1995,
Pubmed
,
Xenbase
Takada,
Midkine, a retinoic acid-inducible heparin-binding cytokine in inflammatory responses: chemotactic activity to neutrophils and association with inflammatory synovitis.
1997,
Pubmed
Tomomura,
A retinoic acid-responsive gene, MK, found in the teratocarcinoma system. Heterogeneity of the transcript and the nature of the translation product.
1990,
Pubmed
Tsutsui,
A new family of heparin-binding growth/differentiation factors: increased midkine expression in Wilms' tumor and other human carcinomas.
1993,
Pubmed
Viola,
Chemokines and their receptors: drug targets in immunity and inflammation.
2008,
Pubmed
Winkler,
Functional divergence of two zebrafish midkine growth factors following fish-specific gene duplication.
2003,
Pubmed
Yan,
High-level soluble expression, purification and characterization of active human midkine from Escherichia coli.
2010,
Pubmed
Yang,
Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6.
1999,
Pubmed
Yoshida,
Expression of the heparin-binding growth factor midkine in the cerebrospinal fluid of patients with neurological disorders.
2008,
Pubmed
You,
Midkine is a NF-kappaB-inducible gene that supports prostate cancer cell survival.
2008,
Pubmed
Zasloff,
Antimicrobial peptides of multicellular organisms.
2002,
Pubmed