Research ArticleCell Biology

Gβγ Activates GSK3 to Promote LRP6-Mediated β-Catenin Transcriptional Activity

See allHide authors and affiliations

Science Signaling  11 May 2010:
Vol. 3, Issue 121, pp. ra37
DOI: 10.1126/scisignal.2000647

You are currently viewing the editor's summary.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

Gβγ for β-Catenin Stability

G proteins influence the Wnt–β-catenin pathway, which regulates various developmental processes; aberrant activity is associated with some cancers. The ligand Wnt interacts with a receptor complex that includes the seven-transmembrane protein Frizzled and the single-transmembrane protein LRP6 to activate the transcriptional regulatory activity of β-catenin. By screening the activity of purified G protein subunits in a Xenopus egg extract system, Jernigan et al. found that, in addition to a subset of Gα subunits, the Gβγ subunit also stabilized β-catenin. Various biochemical analyses, including analysis of transfected mammalian cells and in vitro assays, along with the use of a Gβγ-selective inhibitor, suggested that Gβγ recruited the kinase GSK3 to the membrane. After membrane recruitment, GSK3 phosphorylated LRP6, which then inhibited the β-catenin degradation complex, allowing β-catenin to translocate to the nucleus and activate transcription. Additionally, the Gβγ inhibitor prevented axis duplication of Xenopus embryos under conditions of excess LRP6 activity, thus verifying in vivo a role for Gβγ in this pathway. The Gβγ inhibitor failed to block Wnt-mediated activation of β-catenin, which suggests that a receptor other than Frizzled may activate the G protein that contributes to β-catenin signaling.

View Full Text

Stay Connected to Science Signaling