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Cell signalling

When does Wnt5a turn β-catenin signaling on or off?

Mikels AJ, Nusse R · PLoS biology · 2006

Open access · cc by · source: Europe PMC

Purified Wnt5a can activate or inhibit β-catenin–TCF signaling depending on which Frizzled/receptor context is present.

Study at a glance

Design
Animal / in-vitro — Purified Wnt5a across receptor contexts testing canonical vs inhibitory outputs
N
Receptor-context cell signaling assays — no single sample N
Population
Cells expressing Wnt receptors and responding to purified Wnt5a
Outcome
Context-dependent activation or inhibition of β-catenin–TCF signaling by Wnt5a

Structured fields used in claim comparison tables when every cited study has a complete layer.

Key findings

Receptor expression dictates output: with appropriate Fz receptors, Wnt5a can signal canonically; otherwise it can inhibit β-catenin–TCF pathways—context explains prior controversies.

Methodology

Used purified Wnt5a protein across receptor contexts to resolve whether Wnt5a is intrinsically canonical or noncanonical.

Limitations

One purified ligand study does not map every tissue’s endogenous receptor set.

How this study connects

Role on claims

Each row is a claim on a concept or method page where this paper supports, challenges, or qualifies the statement. Roles are hand-checked — not a model guess.

  • SupportsWestern Blotmethod

    Not every tagged paper is a western-first study. APEX2 maps (22 OMM, 72 ERM proteins) are mass-spectrometry inventories; Wnt5a work uses purified ligand and receptor context to turn β-catenin–TCF signalling on or off; Cas13a plant antiviral work measures GFP and viral accumulation after targeting TuMV regions. Blots may appear as supporting assays, not as the experimental core.

    Evidence for the claim as stated.

  • SupportsWestern Blotmethod

    APEX2, Wnt5a, and Cas13a illustrate false-positive or peripheral lexicon hits: proximity proteomics, ligand/receptor signalling, and CRISPR interference on an RNA virus. Citing them as if they were western-blot method papers overstates how the method was used.

    Evidence for the claim as stated.

  • Purified Wnt5a is not intrinsically canonical or noncanonical: with appropriate Frizzled receptors it can signal through β-catenin–TCF; otherwise it can inhibit that pathway. Receptor context explains prior controversies. A TCF-luciferase (or equivalent) readout is the classic assay here; one purified ligand does not map every tissue's endogenous receptor set.

    Evidence for the claim as stated.

  • Clock-gated auxin reporters and Wnt5a TCF reporters both measure transcription, but one asks 'what time of day' (>10% of seedling genes cycle) and the other asks 'which Frizzled is present'. The same luminescence number cannot be compared across a plant growth assay and a mammalian β-catenin pathway.

    Evidence for the claim as stated.

Open questions

Tensions this paper is part of

From concept pages' “where studies disagree.” Disagreement means the same question; scope means different assays, populations, or outcomes.

  • Scope difference — different assays, populations, or outcomes

    SupportsWestern Blot

    APEX2, Wnt5a, and Cas13a illustrate false-positive or peripheral lexicon hits: proximity proteomics, ligand/receptor signalling, and CRISPR interference on an RNA virus. Citing them as if they were western-blot method papers overstates how the method was used.

  • Scope difference — different assays, populations, or outcomes

    Clock-gated auxin reporters and Wnt5a TCF reporters both measure transcription, but one asks 'what time of day' (>10% of seedling genes cycle) and the other asks 'which Frizzled is present'. The same luminescence number cannot be compared across a plant growth assay and a mammalian β-catenin pathway.

    Also on this tension

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Same topic cluster — not a recommendation engine.