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Sci. Signal., 2 September 2008
Vol. 1, Issue 35, p. re9
[DOI: 10.1126/scisignal.135re9]


Alternative Wnt Signaling Is Initiated by Distinct Receptors

Renée van Amerongen*, Amanda Mikels*, and Roel Nusse{dagger}

Howard Hughes Medical Institute, Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.

* These authors contributed equally to this work.

Gloss: An unresolved question in the field of signal transduction is whether individual ligands within a protein family activate different intracellular pathways downstream of receptor binding or whether these differing pathways are initiated by distinct receptor classes. In this review, which contains 2 figures and 69 references, we examine various Wnt signaling pathways and explore how the historic division of Wnts into "canonical" and "noncanonical" classes has led to a distorted view of Wnt signaling in which the binding of individual Wnts to transmembrane receptor complexes containing Frizzled receptors results in either "canonical" (β-catenin–dependent) or "noncanonical" (β-catenin–independent) signaling. In contrast to this view, research over the past decade suggests that Wnts from either class can elicit β-catenin–dependent and –independent responses and that the outcome is determined by receptor context. Thus, taking the Wnt pathway as an example, we see that signaling output is determined by the receptors present on the cell surface and not by the intrinsic properties of a particular ligand.

{dagger} Corresponding author. E-mail: rnusse{at}

Citation: R. van Amerongen, A. Mikels, R. Nusse, Alternative Wnt Signaling Is Initiated by Distinct Receptors. Sci. Signal. 1, re9 (2008).

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