Gβγ activates GSK3 to promote LRP6-mediated β-catenin transcriptional activity

Kristin K. Jernigan, Christopher S. Cselenyi, Curtis A. Thorne, Alison J. Hanson, Emilios Tahinci, Nicole Hajicek, William M. Oldham, Laura A. Lee, Heidi E. Hamm, John R. Hepler, Tohru Kozasa, Maurine E. Linder, Ethan Lee

Research output: Contribution to journalArticlepeer-review

49 Scopus citations


Evidence from Drosophila and cultured cell studies supports a role for heterotrimeric guanosine triphosphate-binding proteins (G proteins) in Wnt signaling. Wnt inhibits the degradation of the transcriptional regulator β-catenin. We screened the α and βγ subunits of major families of G proteins in a Xenopus egg extract system that reconstitutes β-catenin degradation. We found that Gαo, G αq, Gαi2, and Gβγ inhibited β-catenin degradation. Gβ1γ2 promoted the phosphorylation and activation of the Wnt co-receptor low-density lipoprotein receptor-related protein 6 (LRP6) by recruiting glycogen synthase kinase 3 (GSK3) to the membrane and enhancing its kinase activity. In both a reporter gene assay and an in vivo assay, c-βARK (C-terminal domain of β-adrenergic receptor kinase), an inhibitor of Gβγ, blocked LRP6 activity. Several components of the Wnt-β-catenin pathway formed a complex: Gβ1γ2, LRP6, GSK3, axin, and dishevelled. We propose that free Gβγ and Gα subunits, released from activated G proteins, act cooperatively to inhibit β-catenin degradation and activate β catenin-mediated transcription.

Original languageEnglish (US)
Pages (from-to)ra37
JournalScience signaling
Issue number121
StatePublished - May 11 2010
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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