Journal article
Gβγ Activates GSK3 to Promote LRP6-Mediated β-Catenin Transcriptional Activity
Science signaling, Vol.3(121), pp.ra37-ra37
05/11/2010
DOI: 10.1126/scisignal.2000647
PMCID: PMC3088111
PMID: 20460648
Abstract
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 beta-catenin. We screened the alpha and beta gamma subunits of major families of G proteins in a Xenopus egg extract system that reconstitutes beta-catenin degradation. We found that G alpha(o), G alpha(q), G alpha(i2), and G beta gamma inhibited beta-catenin degradation. G beta(1 gamma 2) 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-beta ARK (C-terminal domain of beta-adrenergic receptor kinase), an inhibitor of G beta gamma, blocked LRP6 activity. Several components of the Wnt-beta-catenin pathway formed a complex: G beta(1 gamma 2), LRP6, GSK3, axin, and dishevelled. We propose that free G beta gamma and G alpha subunits, released from activated G proteins, act cooperatively to inhibit beta-catenin degradation and activate beta-catenin-mediated transcription.
Details
- Title: Subtitle
- Gβγ Activates GSK3 to Promote LRP6-Mediated β-Catenin Transcriptional Activity
- Creators
- Kristin K. Jernigan - Vanderbilt UniversityChristopher S. Cselenyi - Vanderbilt UniversityCurtis A. Thorne - Vanderbilt UniversityAlison J. Hanson - Vanderbilt UniversityEmilios Tahinci - Vanderbilt UniversityNicole Hajicek - University of Illinois Urbana-ChampaignWilliam M. Oldham - Vanderbilt UniversityLaura A. Lee - Vanderbilt UniversityHeidi E Hamm - Vanderbilt UniversityJohn R. Hepler - Emory UniversityTohru Kozasa - University of Illinois Urbana-ChampaignMaurine E. Linder - Cornell UniversityEthan Lee - Vanderbilt University
- Resource Type
- Journal article
- Publication Details
- Science signaling, Vol.3(121), pp.ra37-ra37
- DOI
- 10.1126/scisignal.2000647
- PMID
- 20460648
- PMCID
- PMC3088111
- NLM abbreviation
- Sci Signal
- ISSN
- 1945-0877
- eISSN
- 1937-9145
- Publisher
- Amer Assoc Advancement Science
- Number of pages
- 10
- Grant note
- 5 T 32 DK007563 / Molecular Endocrinology Training Program T32 CA09592 / NIH Cancer Biology Training Program 1 R01 GM081635; GM051466; EY006062; EY010291; NS037112; NS049195 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA 5 T32 GM007347 / National Institute of General Medical Studies Medical Scientist Training Program Pew Charitable Trusts GI SPORE P50 CA95103 / National Cancer Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) 0815094E; 0615279B; 0615162B / American Heart Association (AHA); American Heart Association 0615162B; 0815094E; 0615279B / American Heart Association Predoctoral Fellowships; American Heart Association
- Language
- English
- Date published
- 05/11/2010
- Academic Unit
- Psychiatry
- Record Identifier
- 9984823121802771
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