Cell Biology

Stop and Go Controller

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Science  04 Jun 2010:
Vol. 328, Issue 5983, pp. 1209
DOI: 10.1126/science.328.5983.1209-b

The enzyme glycogen synthase kinase 3 (GSK3) is a protein kinase that originally was named for its role in carbohydrate metabolism. More recently, it's become part of the signaling pathway activated by the secreted morphogen Wnt. In this guise, it phosphorylates the transcription factor β-catenin, which promotes its degradation and abrogates Wnt signaling. When Wnt binds to its receptor, one component of the receptor, LRP6, inhibits GSK3 activity, thus allowing β-catenin to accumulate. But GSK3 also has a positive role in this signaling nexus: phosphorylating LRP6 in a way that enhances signaling and ultimately leads to the inhibition of β-catenin–associated GSK3. In a Xenopus system, Jernigan et al. found that when signals activated G protein–coupled receptors, the G protein βγ subunits bound to GSK3, promoted its translocation to the plasma membrane, and activated its phosphorylation of LRP6. Thus, GSK3 collaborates with other proteins to promote Wnt signaling in addition to holding β-catenin in check until the appropriate signals are given.

Sci. Signal. 3, ra37 (2010).

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