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

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

Source

Purified Wnt5a protein activates or inhibits beta-catenin-TCF signaling depending on receptor context

Mikels AJ, Nusse R · PLoS biology · 2006

doi.org/10.1371/journal.pbio.0040115Read the full paper ↗1,012 citationscc by

What they did

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

What they found

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

The limits

What it doesn't show

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

Key terms

Wnt5a
Wnt family ligand historically labeled noncanonical.
β-catenin–TCF signaling
Canonical Wnt transcriptional pathway.
Frizzled (Fz)
Wnt receptor family guiding pathway choice.
Receptor context
Which receptors/coreceptors a cell expresses.
Canonical vs noncanonical Wnt
β-catenin-dependent vs alternative Wnt outputs.

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Wnt5a output depends on:

Common questions

Is Wnt5a only noncanonical?

No—output depends on receptor context.

What can Wnt5a do to β-catenin–TCF signaling?

Activate or inhibit it.

Key receptor class?

Frizzled receptors.

Why prior conflicts?

Different cellular systems/overexpression contexts.

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