Dkk1

Summary

Gene Symbol: Dkk1
Description: dickkopf WNT signaling pathway inhibitor 1
Alias: dickkopf-related protein 1, dickkopf 1 homolog, dickkopf homolog 1, dickkopf-like protein 1
Species: rat
Products:     Dkk1

Top Publications

  1. Semenov M, Tamai K, Brott B, Kuhl M, Sokol S, He X. Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6. Curr Biol. 2001;11:951-61 pubmed
    ..Our findings suggest that Wnt-Fz-LRP6 complex formation, but not Wnt-Fz interaction, triggers Wnt/beta-catenin signaling. ..
  2. Bafico A, Liu G, Yaniv A, Gazit A, Aaronson S. Novel mechanism of Wnt signalling inhibition mediated by Dickkopf-1 interaction with LRP6/Arrow. Nat Cell Biol. 2001;3:683-6 pubmed
  3. Purro S, Dickins E, Salinas P. The secreted Wnt antagonist Dickkopf-1 is required for amyloid ?-mediated synaptic loss. J Neurosci. 2012;32:3492-8 pubmed publisher
    ..The expression of the Wnt antagonist Dickkopf-1 (Dkk1) is increased in brains of AD patients and in AD transgenic mouse models, suggesting that dysfunction of Wnt ..
  4. David R, Brenner C, Stieber J, Schwarz F, Brunner S, Vollmer M, et al. MesP1 drives vertebrate cardiovascular differentiation through Dkk-1-mediated blockade of Wnt-signalling. Nat Cell Biol. 2008;10:338-45 pubmed publisher
    ..This may also provide a tool to elicit cardiac transdifferentiation in native human adult stem cells. ..
  5. Binnerts M, Kim K, Bright J, Patel S, Tran K, Zhou M, et al. R-Spondin1 regulates Wnt signaling by inhibiting internalization of LRP6. Proc Natl Acad Sci U S A. 2007;104:14700-5 pubmed
    ..Although RSpo1 does not directly activate LRP6, it interferes with DKK1/Kremen-mediated internalization of LRP6 through an interaction with Kremen, resulting in increased LRP6 levels on ..
  6. Morvan F, Boulukos K, Clément Lacroix P, Roman Roman S, Suc Royer I, Vayssière B, et al. Deletion of a single allele of the Dkk1 gene leads to an increase in bone formation and bone mass. J Bone Miner Res. 2006;21:934-45 pubmed
    ..We show that Dkk1, unlike Dkk2, negatively regulates osteoblast differentiation and bone formation...
  7. Niehrs C. Function and biological roles of the Dickkopf family of Wnt modulators. Oncogene. 2006;25:7469-81 pubmed
    Dickkopf (Dkk) genes comprise an evolutionary conserved small gene family of four members (Dkk1-4) and a unique Dkk3-related gene, Dkkl1 (soggy)...
  8. Verani R, Cappuccio I, Spinsanti P, Gradini R, Caruso A, Magnotti M, et al. Expression of the Wnt inhibitor Dickkopf-1 is required for the induction of neural markers in mouse embryonic stem cells differentiating in response to retinoic acid. J Neurochem. 2007;100:242-50 pubmed
    ..These data suggest that induction of Dkk-1 and the ensuing inhibition of the canonical Wnt pathway is required for neural differentiation of ES cells. ..
  9. Adamska M, MacDonald B, Sarmast Z, Oliver E, Meisler M. En1 and Wnt7a interact with Dkk1 during limb development in the mouse. Dev Biol. 2004;272:134-44 pubmed
    ..in Wnt7a null mice, while extra digits result from excess Wnt signaling in mice null for the Wnt antagonist Dkk1. The extra digits and expanded apical ectodermal ridge (AER) of Dkk1-deficient mice closely resemble En1 null mice...

More Information

Publications57

  1. Busceti C, Biagioni F, Aronica E, Riozzi B, Storto M, Battaglia G, et al. Induction of the Wnt inhibitor, Dickkopf-1, is associated with neurodegeneration related to temporal lobe epilepsy. Epilepsia. 2007;48:694-705 pubmed
  2. Zhang Y, Wang S, Zheng Y, Liu A. Possible role of Dickkopf-1 protein in the pathogenesis of tympanosclerosis in a rat model. J Laryngol Otol. 2017;131:860-865 pubmed publisher
    This study aimed to investigate the expression of DKK1 protein in an experimental model of tympanosclerosis and its possible role in the pathogenesis of this disorder...
  3. Wang F, Ko J, Yeh D, Ke H, Wu H. Modulation of Dickkopf-1 attenuates glucocorticoid induction of osteoblast apoptosis, adipocytic differentiation, and bone mass loss. Endocrinology. 2008;149:1793-801 pubmed publisher
    ..The Wnt inhibitor Dickkopf-1 (DKK1) acts as a potent bone-remodeling factor that mediates several types of skeletal disorders...
  4. Caricasole A, Ferraro T, Iacovelli L, Barletta E, Caruso A, Melchiorri D, et al. Functional characterization of WNT7A signaling in PC12 cells: interaction with A FZD5 x LRP6 receptor complex and modulation by Dickkopf proteins. J Biol Chem. 2003;278:37024-31 pubmed
    ..Our functional analysis indicates that WNT7A can specifically act via a Frizzled-5.LRP6 receptor complex in PC12 cells and that this activity can be antagonized by Dickkopf-1 and Dickkopf-3. ..
  5. Klaus A, Birchmeier W. Wnt signalling and its impact on development and cancer. Nat Rev Cancer. 2008;8:387-98 pubmed publisher
    ..Since then, further components of the Wnt pathway have been identified and their epistatic relationships have been defined. This article is a Timeline of crucial discoveries about the components and functions of this essential pathway. ..
  6. Von Marschall Z, Fisher L. Secreted Frizzled-related protein-2 (sFRP2) augments canonical Wnt3a-induced signaling. Biochem Biophys Res Commun. 2010;400:299-304 pubmed publisher
    ..sFRP2 enhancement of Wnt3a signaling was abolished by treatment with the Wnt antagonist, Dickkopf-1 (DKK1)...
  7. Lin S, Li B, Rao S, Yeo E, Hudson T, Nowlin B, et al. Macrophage Wnt7b is critical for kidney repair and regeneration. Proc Natl Acad Sci U S A. 2010;107:4194-9 pubmed publisher
  8. Gong X, Carmon K, Lin Q, Thomas A, Yi J, Liu Q. LGR6 is a high affinity receptor of R-spondins and potentially functions as a tumor suppressor. PLoS ONE. 2012;7:e37137 pubmed publisher
    ..LGR6 is a high affinity receptor for R-spondins 1-3 and potentially functions as a tumor suppressor despite its positive effect on Wnt/?-catenin signaling. ..
  9. Liu H, Zhang J, Song S, Zhao H, Han D, Feng H. A case-control study of the association between tooth-development gene polymorphisms and non-syndromic hypodontia in the Chinese Han population. Eur J Oral Sci. 2012;120:378-85 pubmed publisher
    ..of two markers [rs929387 of GLI family zinc finger 3 (GLI3) and rs11001553 of Dickkopf-related protein 1 (DKK1)]...
  10. Wang F, Ko J, Lin C, Wu H, Ke H, Tai P. Knocking down dickkopf-1 alleviates estrogen deficiency induction of bone loss. A histomorphological study in ovariectomized rats. Bone. 2007;40:485-92 pubmed
    Dickkopf-1 (DKK1) has been found to act as a potent Wnt signaling-inhibitory factor for regulating skeletal disorders...
  11. Björklund P, Akerstrom G, Westin G. An LRP5 receptor with internal deletion in hyperparathyroid tumors with implications for deregulated WNT/beta-catenin signaling. PLoS Med. 2007;4:e328 pubmed
    ..Mechanisms that may account for this activation have not been identified, except for a few cases of beta-catenin (CTNNB1) stabilizing mutation in pHPT tumors...
  12. Pang L, Dong N, Wang D, Zhang N, Xing J. Increased Dickkopf-1 expression is correlated with poisoning severity in carbon monoxide-poisoned humans and rats. Inhal Toxicol. 2016;28:455-62 pubmed publisher
    ..DKK-1 appears to have potential utility in providing valuable information for determining the severity and damage of CO poisoning. ..
  13. Guo Y, Mishra A, Howland E, Zhao C, Shukla D, Weng T, et al. Platelet-derived Wnt antagonist Dickkopf-1 is implicated in ICAM-1/VCAM-1-mediated neutrophilic acute lung inflammation. Blood. 2015;126:2220-9 pubmed publisher
    ..Here, we identified platelet-derived Dickkopf-1 (Dkk1) as the major Wnt antagonist contributing to the suppression of Wnt/β-catenin signaling in AECs during acute ..
  14. Zhang Q, Wang R, Khan M, Mahesh V, Brann D. Role of Dickkopf-1, an antagonist of the Wnt/beta-catenin signaling pathway, in estrogen-induced neuroprotection and attenuation of tau phosphorylation. J Neurosci. 2008;28:8430-41 pubmed publisher
    ..levels of E2 protects the hippocampus CA1 against global cerebral ischemia by preventing elevation of dickkopf-1 (Dkk1), an antagonist of the Wnt/beta-catenin signaling pathway, which is a principal mediator of neurodegeneration in ..
  15. Dietrich M, van der Weyden L, Prosser H, Bradley A, Herz J, Adams D. Ectodomains of the LDL receptor-related proteins LRP1b and LRP4 have anchorage independent functions in vivo. PLoS ONE. 2010;5:e9960 pubmed publisher
  16. Caruso A, Motolese M, Iacovelli L, Caraci F, Copani A, Nicoletti F, et al. Inhibition of the canonical Wnt signaling pathway by apolipoprotein E4 in PC12 cells. J Neurochem. 2006;98:364-71 pubmed
    ..We conclude that ApoE4 behaves as an inhibitor of the canonical Wnt pathway in a context-independent manner. ..
  17. Yanagita M, Oka M, Watabe T, Iguchi H, Niida A, Takahashi S, et al. USAG-1: a bone morphogenetic protein antagonist abundantly expressed in the kidney. Biochem Biophys Res Commun. 2004;316:490-500 pubmed
    ..Collectively, we suggest that USAG-1 is a BMP antagonist that interacts with BMP-7 in the developing and adult kidney. ..
  18. Dun Y, Li G, Yang Y, Xiong Z, Feng M, Wang M, et al. Inhibition of the canonical Wnt pathway by Dickkopf-1 contributes to the neurodegeneration in 6-OHDA-lesioned rats. Neurosci Lett. 2012;525:83-8 pubmed publisher
    Dickkopf-1 (Dkk1), an antagonist of the Wnt/?-catenin pathway, has been implicated in many neurodegenerative diseases. However, it's unknown whether Dkk1 is involved in the pathogenesis of Parkinson's disease...
  19. Galli S, Lopes D, Ammari R, Kopra J, Millar S, Gibb A, et al. Deficient Wnt signalling triggers striatal synaptic degeneration and impaired motor behaviour in adult mice. Nat Commun. 2014;5:4992 pubmed publisher
    ..Inducible expression of the secreted Wnt antagonist Dickkopf1 (Dkk1) in adult mice (iDkk1) decreases the number of cortico-striatal glutamatergic synapses and of D1 and D2 dopamine ..
  20. Satoh W, Matsuyama M, Takemura H, Aizawa S, Shimono A. Sfrp1, Sfrp2, and Sfrp5 regulate the Wnt/beta-catenin and the planar cell polarity pathways during early trunk formation in mouse. Genesis. 2008;46:92-103 pubmed publisher
    ..Furthermore, Dkk1-deficient embryos carrying Sfrp1 homozygous and Sfrp2 heterozygous mutations display irregular somites and ..
  21. Lin C, Wang J, Ko J, Huang Y, Kuo Y, Wang F. Dickkopf-1 promotes hyperglycemia-induced accumulation of mesangial matrix and renal dysfunction. J Am Soc Nephrol. 2010;21:124-35 pubmed publisher
    ..In vitro, HG increased expression of DKK1, receptor Kremen-2, TGF-beta1, and fibronectin in mesangial cells...
  22. Hie M, Iitsuka N, Otsuka T, Tsukamoto I. Insulin-dependent diabetes mellitus decreases osteoblastogenesis associated with the inhibition of Wnt signaling through increased expression of Sost and Dkk1 and inhibition of Akt activation. Int J Mol Med. 2011;28:455-62 pubmed publisher
    ..The activation of Akt was inhibited. The mRNA and protein levels of sclerosteosis (Sost) and Dickkopf 1 (Dkk1), inhibitors of Wnt signaling, increased...
  23. Lewis S, Khoo P, Andrea De Young R, Bildsoe H, Wakamiya M, Behringer R, et al. Genetic interaction of Gsc and Dkk1 in head morphogenesis of the mouse. Mech Dev. 2007;124:157-165 pubmed
    Mouse embryos lacking Gsc and Dkk1 function display severe deficiencies in craniofacial structures which are not found in either Dkk1 homozygous null or Gsc homozygous null mutant embryos...
  24. Killick R, Ribe E, Al Shawi R, Malik B, Hooper C, Fernandes C, et al. Clusterin regulates ?-amyloid toxicity via Dickkopf-1-driven induction of the wnt-PCP-JNK pathway. Mol Psychiatry. 2014;19:88-98 pubmed publisher
    ..remained elusive, it is known to increase the expression of the antagonist of canonical wnt signalling, Dickkopf-1 (Dkk1), whereas the silencing of Dkk1 blocks A? neurotoxicity...
  25. Min J, Park H, Choi H, Kim Y, Pyun B, Agrawal V, et al. The WNT antagonist Dickkopf2 promotes angiogenesis in rodent and human endothelial cells. J Clin Invest. 2011;121:1882-93 pubmed publisher
    ..Here, we report that Dickkopf1 (DKK1) and Dickkopf2 (DKK2), originally known as WNT antagonists, play opposite functional roles in regulating ..
  26. Carter M, Chen X, Slowinska B, Minnerath S, Glickstein S, Shi L, et al. Crooked tail (Cd) model of human folate-responsive neural tube defects is mutated in Wnt coreceptor lipoprotein receptor-related protein 6. Proc Natl Acad Sci U S A. 2005;102:12843-8 pubmed
    ..Mutant LRP6 binds to Wnt and Dickkopf1 (Dkk1) but not Mesd1, and Dkk1 cannot antagonize Wnt in Cd/Cd cells, resulting in hyperactivity...
  27. Li L, Mao J, Sun L, Liu W, Wu D. Second cysteine-rich domain of Dickkopf-2 activates canonical Wnt signaling pathway via LRP-6 independently of dishevelled. J Biol Chem. 2002;277:5977-81 pubmed
    ..All the evidence indicates that Dkk-2C2 signals through LRP proteins, which does not require Dvl, while Wnt protein may employ both Dvl, presumably through Fz, and LRP to achieve more efficient signal transduction. ..
  28. Barbolina M, Liu Y, Gurler H, Kim M, Kajdacsy Balla A, Rooper L, et al. Matrix rigidity activates Wnt signaling through down-regulation of Dickkopf-1 protein. J Biol Chem. 2013;288:141-51 pubmed publisher
    ..Similar results were obtained in other tissue-invasive cells such as vascular endothelial cells, suggesting a novel mechanism for functional coupling of matrix adhesion with Wnt signaling. ..
  29. Li X, Grisanti M, Fan W, Asuncion F, Tan H, Dwyer D, et al. Dickkopf-1 regulates bone formation in young growing rodents and upon traumatic injury. J Bone Miner Res. 2011;26:2610-21 pubmed publisher
    The physiological role of Dickkopf-1 (Dkk1) during postnatal bone growth in rodents and in adult rodents was examined utilizing an antibody to Dkk1 (Dkk1-Ab) that blocked Dkk1 binding to both low density lipoprotein receptor-related ..
  30. Cho S, Her S, Sun H, Choi O, Yang J, Kim S, et al. Differential effects of secreted frizzled-related proteins (sFRPs) on osteoblastic differentiation of mouse mesenchymal cells and apoptosis of osteoblasts. Biochem Biophys Res Commun. 2008;367:399-405 pubmed publisher
    ..In conclusion, we found that different repertoires of sFRPs exert differential effects on osteoblastic differentiation of mouse mesenchymal cells and cellular apoptosis of mouse osteoblasts in vitro. ..
  31. Bhat R, Stauffer B, Della Pietra A, Bodine P. Wnt3-frizzled 1 chimera as a model to study canonical Wnt signaling. J Cell Biochem. 2010;109:876-84 pubmed publisher
    ..In addition, this methodology can be utilized to identify inhibitors of either Wnt, Fz or interactors of the canonical pathway, which may have potential therapeutic value in the treatment of cancers and other diseases. ..
  32. Semenov M, Zhang X, He X. DKK1 antagonizes Wnt signaling without promotion of LRP6 internalization and degradation. J Biol Chem. 2008;283:21427-32 pubmed publisher
    b>DKK1 is a secreted protein that antagonizes Wnt signaling and plays essential roles in vertebrate embryogenesis including head induction, skeletal development, and limb patterning...
  33. Bryja V, Schulte G, Arenas E. Wnt-3a utilizes a novel low dose and rapid pathway that does not require casein kinase 1-mediated phosphorylation of Dvl to activate beta-catenin. Cell Signal. 2007;19:610-6 pubmed
    ..The increase in beta-catenin activation by Wnt-3a (PS-Dvl-dependent or -independent) were blocked by Dickkopf1 (Dkk1), suggesting that the effect of Wnt-3a is in both cases mediated by Lrp5/6 receptors...
  34. Dun Y, Yang Y, Xiong Z, Feng M, Zhang Y, Wang M, et al. Induction of Dickkopf-1 contributes to the neurotoxicity of MPP+ in PC12 cells via inhibition of the canonical Wnt signaling pathway. Neuropharmacology. 2013;67:168-75 pubmed publisher
    The secreted glycoprotein Dickkopf-1 (Dkk1), an antagonist of the Wnt/?-catenin pathway, has been implicated in many neurodegenerative diseases...
  35. Abu Elmagd M, Robson L, Sweetman D, Hadley J, Francis West P, Munsterberg A. Wnt/Lef1 signaling acts via Pitx2 to regulate somite myogenesis. Dev Biol. 2010;337:211-9 pubmed publisher
  36. Strakovsky R, Pan Y. A decrease in DKK1, a WNT inhibitor, contributes to placental lipid accumulation in an obesity-prone rat model. Biol Reprod. 2012;86:81 pubmed publisher
    ..analysis, and frozen placental sections were analyzed for fat accumulation as well as beta-catenin and Dickkopf homolog 1 (Xenopus laevis) (DKK1) localization...
  37. González Sancho J, Brennan K, Castelo Soccio L, Brown A. Wnt proteins induce dishevelled phosphorylation via an LRP5/6- independent mechanism, irrespective of their ability to stabilize beta-catenin. Mol Cell Biol. 2004;24:4757-68 pubmed
    ..Our data also present Dvl phosphorylation as a general biochemical assay for Wnt protein function, including those Wnts that do not activate the Wnt/beta-catenin pathway. ..
  38. Bourhis E, Tam C, Franke Y, Bazan J, Ernst J, Hwang J, et al. Reconstitution of a frizzled8.Wnt3a.LRP6 signaling complex reveals multiple Wnt and Dkk1 binding sites on LRP6. J Biol Chem. 2010;285:9172-9 pubmed publisher
    ..We determine the binding affinities of Wnts and Dickkopf 1 (Dkk1) to the relevant co-receptors and reconstitute in vitro the Fz8 CRD.Wnt3a.LRP6 signaling complex...
  39. Paige S, Osugi T, Afanasiev O, Pabon L, Reinecke H, Murry C. Endogenous Wnt/beta-catenin signaling is required for cardiac differentiation in human embryonic stem cells. PLoS ONE. 2010;5:e11134 pubmed publisher
    ..of induction enhanced cardiac differentiation, while early inhibition of endogenous Wnt/beta-catenin signaling with Dkk1 inhibited cardiac differentiation, as indicated by quantitative RT-PCR analysis for beta-myosin heavy chain (beta-..
  40. Xu Y, Xu B, Wu C, Wu Y, Tong P, Xiao L. Dynamic expression of DKK1 protein in the process whereby Epimedium-derived flavonoids up-regulate osteogenic and down-regulate adipogenic differentiation of bone marrow stromal cells in ovariectomized rats. Orthop Surg. 2011;3:119-26 pubmed publisher
    To observe the dynamic expression of DKK1 protein in the process whereby Epimedium-derived flavonoids (EFs) regulate the balance between osteogenic and adipogenic differentiation of bone marrow stromal cells in ovariectomized rats, and to ..
  41. Weng L, Wang C, Ko J, Sun Y, Wang F. Control of Dkk-1 ameliorates chondrocyte apoptosis, cartilage destruction, and subchondral bone deterioration in osteoarthritic knees. Arthritis Rheum. 2010;62:1393-402 pubmed publisher
    ..Interference with the cartilage- and bone-deleterious actions of Dkk-1 provides therapeutic potential for alleviating cartilage destruction and subchondral bone damage in OA knee joints. ..
  42. Causeret F, Sumia I, Pierani A. Kremen1 and Dickkopf1 control cell survival in a Wnt-independent manner. Cell Death Differ. 2016;23:323-32 pubmed publisher
    ..Our findings thus reveal a new Wnt-independent function for Kremen1 and Dickkopf1 in the regulation of cell survival with potential implications in cancer therapies. ..
  43. Li M, Cai H, Yang Y, Zhang J, Sun K, Yan Y, et al. Perichondrium mesenchymal stem cells inhibit the growth of breast cancer cells via the DKK-1/Wnt/?-catenin signaling pathway. Oncol Rep. 2016;36:936-44 pubmed publisher
    ..DKK-1 secreted by PMSCs played a vital role in controlling the Wnt/?-catenin signaling pathway in breast cancer. ..
  44. Liu F, Thirumangalathu S, Gallant N, Yang S, Stoick Cooper C, Reddy S, et al. Wnt-beta-catenin signaling initiates taste papilla development. Nat Genet. 2007;39:106-12 pubmed
    ..genetic deletion of epithelial beta-catenin or inhibition of Wnt-beta-catenin signaling by ectopic dickkopf1 (Dkk1) blocks initiation of fungiform papilla morphogenesis...
  45. Ellwanger K, Saito H, Clément Lacroix P, Maltry N, Niedermeyer J, Lee W, et al. Targeted disruption of the Wnt regulator Kremen induces limb defects and high bone density. Mol Cell Biol. 2008;28:4875-82 pubmed publisher
    Kremen1 and Kremen2 (Krm1 and Krm2) are transmembrane coreceptors for Dickkopf1 (Dkk1), an antagonist of Wnt/beta-catenin signaling. The physiological relevance of Kremen proteins in mammals as Wnt modulators is unresolved...
  46. Ribeiro D, Ellwanger K, Glagow D, Theofilopoulos S, Corsini N, Martin Villalba A, et al. Dkk1 regulates ventral midbrain dopaminergic differentiation and morphogenesis. PLoS ONE. 2011;6:e15786 pubmed publisher
    Dickkopf1 (Dkk1) is a Wnt/?-catenin inhibitor that participates in many processes during embryonic development...
  47. Brugmann S, Goodnough L, Gregorieff A, Leucht P, ten Berge D, Fuerer C, et al. Wnt signaling mediates regional specification in the vertebrate face. Development. 2007;134:3283-95 pubmed
    ..We also used a biochemical approach to perturb Wnt signaling and found that in utero delivery of a Wnt antagonist, Dkk1, produced similar midfacial malformations...
  48. Li Y, Chen J, Lu W, McCormick L, Wang J, Bu G. Mesd binds to mature LDL-receptor-related protein-6 and antagonizes ligand binding. J Cell Sci. 2005;118:5305-14 pubmed
    ..Together our results show that in addition to serving as a folding chaperone, Mesd can function as a receptor antagonist by inhibiting ligand binding to mature LRP6. ..