For the best experience on the Abcam website please upgrade to a modern browser such as Google Chrome

Hello. We're improving abcam.com and we'd welcome your feedback.

Hello. We're improving abcam.com and we'd welcome your feedback.

Infomation icon

We haven't added this to the BETA yet

New BETA website

New BETA website

Hello. We're improving abcam.com and we'd welcome your feedback.

Take a look at our BETA site and see what we’ve done so far.

Switch on our new BETA site

Now available

Search and browse selected products

  • A selection of primary antibodies

Purchase these through your usual distributor

In the coming months

  • Additional product types
  • Supporting content
  • Sign in to your account
  • Purchase online
United States
Your country/region is currently set to:

If incorrect, please enter your country/region into the box below, to view site information related to your country/region.

Call (888) 77-ABCAM (22226) or contact us
Need help? Contact us

  • My account
  • Sign out
Sign in or Register with us

Welcome

Sign in or

Don't have an account?

Register with us
My basket
Quick order
Abcam homepage

  • Research Products
    By product type
    Primary antibodies
    Secondary antibodies
    ELISA and Matched Antibody Pair Kits
    Cell and tissue imaging tools
    Cellular and biochemical assays
    Proteins and Peptides
    By product type
    Proteomics tools
    Agonists, activators, antagonists and inhibitors
    Cell lines and Lysates
    Multiplex miRNA assays
    Multiplex Assays
    By research area
    Cancer
    Cardiovascular
    Cell Biology
    Epigenetics
    Metabolism
    Developmental Biology
    By research area
    Immunology
    Microbiology
    Neuroscience
    Signal Transduction
    Stem Cells
  • Customized Products & Partnerships
    Customized Products & Partnerships

    Customized products and commercial partnerships to accelerate your diagnostic and therapeutic programs.

    Customized products

    Partner with us

  • Support
    Support hub

    Access advice and support for any research roadblock

    View support hub

    Protocols

    Your experiments laid out step by step

    View protocols

  • Events
    • Conference calendar
    • Cancer
    • Cardiovascular
    • Epigenetics & Nuclear signaling
    • Immunology
    • Neuroscience
    • Stem cells
    • Tradeshows
    • Scientific webinars
    Keep up to date with the latest events

    Full event breakdown with abstracts, speakers, registration and more

    View global event calendar

  • Pathways
    Cell signalling pathways

    View all pathways

    View all interactive pathways

An overview of Wnt signaling

Related

  • Wnt signaling resources
    • Wnt pathway modulators & inhibitors
      • All interactive pathways

        ​​Wnt proteins are a family of cysteine-rich glycoproteins that play a critical role during development and in cancer. Our interactive Wnt signaling poster highlights the three Wnt signaling pathways: the canonical beta-catenin and the non-canonical planar cell polarity, and Wnt/Ca2+ pathways

        Download the Wnt signaling pathway poster here

        Overview of Wnt signaling

        There are 19 human WNT genes, several of which encode additional alternatively spliced isoforms1,2. Wnt proteins initiate signaling through binding Frizzled receptors, which contain seven transmembrane spanning domains. Ten Frizzled receptors have been identified in humans. Signal specificity may be achieved through cell-specific expression of different Frizzled receptors, which can form homo- and hetero-oligomers, or through the association of Frizzled receptors with different co-receptors3.

        In the absence of Wnt, the signaling pool of beta-catenin is maintained at low levels through degradation4–6. Beta-catenin is targeted for ubiquitination by the beta-transducin repeat-containing protein (β-TrCP) and is then degraded by the proteasome. Beta-catenin is phosphorylated by the serine/threonine kinases casein kinase 1 (CK1) and glycogen synthase kinase 3 beta (GSK3β). Phosphorylation of beta-catenin occurs in a multi-protein complex (the destruction complex), which comprises axin, adenomatous polyposis coli (APC) protein, and diversin. Upon receipt of a Wnt signal, the protein Dishevelled (Dsh) prevents degradation of beta-catenin, possibly through the recruitment of GBP/Frat-1, which in turn displaces GSK3β from the destruction complex. LRP5/6, members of the low-density lipoprotein receptor-related protein family, serve as co-receptors for beta-catenin-dependent Wnt signaling. Frodo and beta-arrestin act synergistically with Dsh, whilst Dapper has been identified as an antagonist of Dsh.

        What to expect from our Wnt pathway poster?

        This interactive pathway poster features all three known Wnt signaling pathways: the beta-catenin (canonical) pathway, the planar cell polarity pathway, and the Wnt/Ca2+ pathway. All three pathways are activated by binding of a Wnt-protein ligand to a Frizzled family receptor; however, they follow unique transduction cascades and harbor different proteins.

        • Understand the key differences between the three types of Wnt signaling 
        • Explore Wnt ligands, agonists, antagonists, and their interactions with Wnt receptors
        • Find the right products to advance your research


        The beta-catenin pathway

        Stabilized beta-catenin enters the nucleus and associates with T cell factor (TCF)/lymphoid enhancer factor (LEF) transcription factors, which leads to the transcription of Wnt target genes such as cyclin D1, PPARD, and twin.

        In the absence of a Wnt signal, TCF/LEF family members interact with transcriptional inhibitors such as Groucho, which serve to repress Wnt signaling. The repressing effect of Groucho is mediated by interactions with histone deacetylases (HDAC), which are thought to make DNA refractory to transcriptional activation.

        Negative regulators of beta-catenin signaling include ICAT and duplin, which directly bind to beta-catenin preventing it from interacting with TCF/LEF7. In addition to its role in Wnt signaling, beta-catenin plays a role in cell adhesion through binding to the cytoplasmic domain of type 1 cadherins and linking them through alpha-catenin to the actin cytoskeleton.

        The planar cell polarity pathway

        In the planar cell polarity pathway, Wnt signaling through Frizzled receptors mediates asymmetric cytoskeletal organization and the polarization of cells by inducing modifications to the actin cytoskeleton. Two independent pathways that are initiated by Dsh trigger the activation of the small GTPases Rho and Rac. Activation of Rho requires Daam-1 and leads in turn to the activation of the Rho-associated kinase ROCK. Rac activation is independent of Daam-1 and stimulates Jun Kinase (JNK) activity5,8.

        The Wnt/Ca2+ pathway

        Wnt signaling via Frizzled receptors can also lead to the release of intracellular calcium. Frizzled co-receptors, involved in this pathway include Knypek and Ror2. Other intracellular second messengers associated with this pathway include heterotrimeric G-proteins, phospholipase C (PLC), and protein kinase C (PKC). The exact genes activated by the Wnt/Ca2+ pathway are unknown, but NFAT appears to be involved, which is a transcription factor regulated by the calcium/calmodulin-dependent protein phosphatase, calcineurin. The Wnt/Ca2+ pathway is important for cell adhesion and cell movements during gastrulation3,8.

        Antagonists of Wnt signaling

        Wnt antagonists can be divided into two functional classes: the secreted Frizzled related proteins (sFRP class) and the Dickkopf (Dkk) class2. Members of the sFRP class include the sFRP family (sFRP1-5), Wnt inhibitory factor-1 (WIF-1), and Cerberus. These antagonists bind directly to Wnt and alter their ability to bind to the Wnt receptor complex.

        In contrast, members of the Dickkopf class (Dkk1-4) inhibit Wnt signaling by binding to LRP5/LRP6. Kremen, which binds to Dkk is thought to trigger the internalization and clearing of the Dkk–LRP complex from the cell surface. The segregation and internalization of LRP thereby render Wnt unable to activate intracellular signaling9,10. Thus, in theory, antagonists of the sFRP class inhibit both canonical and noncanonical Wnt signaling pathways, whereas those of the Dickkopf class specifically inhibit beta-catenin-dependent canonical Wnt signaling.

        References

        1.    Miller JR (2001). The Wnts. Genome Biol, 3(1).

        2.    Kawano Y & Kypta R, 2003. Secreted antagonists of the Wnt signaling pathway. J Cell Sci, 116(13): 2627–34.

        3.    Kohn AD & Moon RT (2005). Wnt and calcium signaling beta-catenin-independent pathways. Cell calcium, 38(3-4): 439–46.

        4.    Dale TC (1998). Signal transduction by the Wnt family of ligands. Biochem J, 329(2): 209–23.

        5.    Huelsken J & Behrens J (2002). The Wnt signaling pathway. J Cell Sci, 115(21): 3977–8.

        6.    Nusse R (2005). Wnt signaling in disease and in development. Cell Res, 15(1): 28–32.

        7.    Kikuchi A, Kichida S, Yamamoto H (2006). Regulation of Wnt signaling by protein-protein interaction and post-translational modifications. Exp Mol Med, 38(1): 1–10.

        8.    Habas R & Dawid IB (2005). Dishevelled and Wnt signaling: is the nucleus the final frontier? J Biol, 4(1): 2.

        9.    Mao B, Wu W, Davidson G, Marhold J, Li M, Mechler BM, Delius H, Hoppe D, Stannek P, Walter C, Glinka A, Niehrs C (2002). Kremen proteins are Dickkopf receptors that regulate Wnt/beta-catenin signaling. Nature, 417(6889): 664–7.

        10.  Rothbächer U & Lemaire P (2002). Créme de la Kremen of Wnt signaling inhibition. Nat Cell Biol, 4(7): E172–3.


        Get resources and offers direct to your inbox Sign up
        A-Z by research area
        • Cancer
        • Cardiovascular
        • Cell biology
        • Developmental biology
        • Epigenetics & Nuclear signaling
        • Immunology
        • Metabolism
        • Microbiology
        • Neuroscience
        • Signal transduction
        • Stem cells
        A-Z by product type
        • Primary antibodies
        • Secondary antibodies
        • Biochemicals
        • Isotype controls
        • Flow cytometry multi-color selector
        • Kits
        • Loading controls
        • Lysates
        • Peptides
        • Proteins
        • Slides
        • Tags and cell markers
        • Tools & Reagents
        Help & support
        • Support
        • Make an Inquiry
        • Protocols & troubleshooting
        • Placing an order
        • RabMAb products
        • Biochemical product FAQs
        • Training
        • Browse by Target
        Company
        • Corporate site
        • Investor relations
        • Company news
        • Careers
        • About us
        • Blog
        Events
        • Tradeshows
        • Conferences
        International websites
        • abcam.cn
        • abcam.co.jp

        Join with us

        • LinkedIn
        • facebook
        • Twitter
        • YouTube
        • Terms of sale
        • Website terms of use
        • Cookie policy
        • Privacy policy
        • Legal
        • Modern slavery statement
        © 1998-2022 Abcam plc. All rights reserved.