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.

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What determines Wnt5a signaling output?

Receptor context / which Fz receptor is expressed.

Can Wnt5a signal canonically?

Yes—when coexpressed with the appropriate Fz receptor.

What pathway can Wnt5a activate or inhibit?

β-catenin–TCF signaling.

Why do Wnt controversies arise?

Varied cellular systems plus prior overexpression approaches.

What ligand form did authors use?

Purified Wnt5a protein.

What coreceptors pair with Fz in canonical Wnt?

LRP5/6.

Historical grouping of Wnts was based on what?

Canonical signaling ability without regard to cellular context.

Example conflicting Wnt5a report?

Overexpression inhibiting canonical signaling via β-catenin degradation.

What precise regulation prevents inappropriate Wnt activation?

Tight control of pathway components/context.

Student takeaway?

Ligand identity alone does not fix pathway output—receptors do.