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Sci Signal
2010 May 11;3121:ra37. doi: 10.1126/scisignal.2000647.
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Gbetagamma activates GSK3 to promote LRP6-mediated beta-catenin transcriptional activity.
Jernigan KK
,
Cselenyi CS
,
Thorne CA
,
Hanson AJ
,
Tahinci E
,
Hajicek N
,
Oldham WM
,
Lee LA
,
Hamm HE
,
Hepler JR
,
Kozasa T
,
Linder ME
,
Lee E
.
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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 betagamma subunits of major families of G proteins in a Xenopus egg extract system that reconstitutes beta-catenin degradation. We found that Galpha(o), Galpha(q), Galpha(i2), and Gbetagamma inhibited beta-catenin degradation. Gbeta(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-betaARK (C-terminal domain of beta-adrenergic receptor kinase), an inhibitor of Gbetagamma, blocked LRP6 activity. Several components of the Wnt-beta-catenin pathway formed a complex: Gbeta(1)gamma(2), LRP6, GSK3, axin, and dishevelled. We propose that free Gbetagamma and Galpha subunits, released from activated G proteins, act cooperatively to inhibit beta-catenin degradation and activate beta-catenin-mediated transcription.
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20460648
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Angers,
The KLHL12-Cullin-3 ubiquitin ligase negatively regulates the Wnt-beta-catenin pathway by targeting Dishevelled for degradation.
2006, Pubmed,
Xenbase
Angers,
The KLHL12-Cullin-3 ubiquitin ligase negatively regulates the Wnt-beta-catenin pathway by targeting Dishevelled for degradation.
2006,
Pubmed
,
Xenbase
Bilic,
Wnt induces LRP6 signalosomes and promotes dishevelled-dependent LRP6 phosphorylation.
2007,
Pubmed
Blow,
Chromosome replication in cell-free systems from Xenopus eggs.
1987,
Pubmed
,
Xenbase
Cselenyi,
LRP6 transduces a canonical Wnt signal independently of Axin degradation by inhibiting GSK3's phosphorylation of beta-catenin.
2008,
Pubmed
,
Xenbase
Davidson,
Casein kinase 1 gamma couples Wnt receptor activation to cytoplasmic signal transduction.
2005,
Pubmed
,
Xenbase
Davis,
Structural and molecular characterization of a preferred protein interaction surface on G protein beta gamma subunits.
2005,
Pubmed
Egger-Adam,
The trimeric G protein Go inflicts a double impact on axin in the Wnt/frizzled signaling pathway.
2010,
Pubmed
Ford,
Molecular basis for interactions of G protein betagamma subunits with effectors.
1998,
Pubmed
Fujino,
Phosphorylation of glycogen synthase kinase-3 and stimulation of T-cell factor signaling following activation of EP2 and EP4 prostanoid receptors by prostaglandin E2.
2002,
Pubmed
Galés,
Real-time monitoring of receptor and G-protein interactions in living cells.
2005,
Pubmed
Gao,
Inositol pentakisphosphate mediates Wnt/beta-catenin signaling.
2007,
Pubmed
Gard,
Microtubule assembly in cytoplasmic extracts of Xenopus oocytes and eggs.
1987,
Pubmed
,
Xenbase
Gard,
A microtubule-associated protein from Xenopus eggs that specifically promotes assembly at the plus-end.
1987,
Pubmed
,
Xenbase
Gardner,
Nuclear stabilization of beta-catenin and inactivation of glycogen synthase kinase-3beta by gonadotropin-releasing hormone: targeting Wnt signaling in the pituitary gonadotrope.
2007,
Pubmed
Hepler,
Purification from Sf9 cells and characterization of recombinant Gq alpha and G11 alpha. Activation of purified phospholipase C isozymes by G alpha subunits.
1993,
Pubmed
Hepler,
Purification of recombinant Gq alpha, G11 alpha, and G16 alpha from Sf9 cells.
1994,
Pubmed
Hwang,
Silencing the expression of multiple Gbeta-subunits eliminates signaling mediated by all four families of G proteins.
2005,
Pubmed
Jung,
Negative feedback regulation of Wnt signaling by Gbetagamma-mediated reduction of Dishevelled.
2009,
Pubmed
,
Xenbase
Katanaev,
Trimeric G protein-dependent frizzled signaling in Drosophila.
2005,
Pubmed
Koch,
Cellular expression of the carboxyl terminus of a G protein-coupled receptor kinase attenuates G beta gamma-mediated signaling.
1994,
Pubmed
Kornbluth,
Evidence for a dual role for TC4 protein in regulating nuclear structure and cell cycle progression.
1994,
Pubmed
,
Xenbase
Kreutz,
A new approach to producing functional G alpha subunits yields the activated and deactivated structures of G alpha(12/13) proteins.
2006,
Pubmed
Krumins,
Targeted knockdown of G protein subunits selectively prevents receptor-mediated modulation of effectors and reveals complex changes in non-targeted signaling proteins.
2006,
Pubmed
Lee,
Expression of G-protein alpha subunits in Escherichia coli.
1994,
Pubmed
Linder,
Purification and characterization of Go alpha and three types of Gi alpha after expression in Escherichia coli.
1990,
Pubmed
Linder,
Purification of recombinant Gi alpha and Go alpha proteins from Escherichia coli.
1991,
Pubmed
Liu,
G protein signaling from activated rat frizzled-1 to the beta-catenin-Lef-Tcf pathway.
2001,
Pubmed
,
Xenbase
Ma,
Corequirement of specific phosphoinositides and small GTP-binding protein Cdc42 in inducing actin assembly in Xenopus egg extracts.
1998,
Pubmed
,
Xenbase
MacDonald,
Wnt/beta-catenin signaling: components, mechanisms, and diseases.
2009,
Pubmed
,
Xenbase
Najafi,
Activators of G proteins inhibit GSK-3beta and stabilize beta-Catenin in Xenopus oocytes.
2009,
Pubmed
,
Xenbase
Papermaster,
Rhodopsin content in the outer segment membranes of bovine and frog retinal rods.
1974,
Pubmed
Peng,
Xenopus laevis: Practical uses in cell and molecular biology. Solutions and protocols.
1991,
Pubmed
,
Xenbase
Piao,
Direct inhibition of GSK3beta by the phosphorylated cytoplasmic domain of LRP6 in Wnt/beta-catenin signaling.
2008,
Pubmed
,
Xenbase
Roychowdhury,
G protein beta1gamma2 subunits promote microtubule assembly.
1997,
Pubmed
Salic,
Control of beta-catenin stability: reconstitution of the cytoplasmic steps of the wnt pathway in Xenopus egg extracts.
2000,
Pubmed
,
Xenbase
Scott,
Evidence that a protein-protein interaction 'hot spot' on heterotrimeric G protein betagamma subunits is used for recognition of a subclass of effectors.
2001,
Pubmed
Smrcka,
G protein βγ subunits: central mediators of G protein-coupled receptor signaling.
2008,
Pubmed
Sokol,
Analysis of Dishevelled signalling pathways during Xenopus development.
1996,
Pubmed
,
Xenbase
Speirs,
Prostaglandin Gbetagamma signaling stimulates gastrulation movements by limiting cell adhesion through Snai1a stabilization.
2010,
Pubmed
Sternweis,
Isolation of two proteins with high affinity for guanine nucleotides from membranes of bovine brain.
1984,
Pubmed
Tamai,
LDL-receptor-related proteins in Wnt signal transduction.
2000,
Pubmed
,
Xenbase
Tamai,
A mechanism for Wnt coreceptor activation.
2004,
Pubmed
,
Xenbase
Taussig,
Inhibition of adenylyl cyclase by Gi alpha.
1993,
Pubmed
Ueda,
G protein beta gamma subunits. Simplified purification and properties of novel isoforms.
1994,
Pubmed
Wan,
Parathyroid hormone signaling through low-density lipoprotein-related protein 6.
2008,
Pubmed
,
Xenbase
Wu,
Inhibition of GSK3 phosphorylation of beta-catenin via phosphorylated PPPSPXS motifs of Wnt coreceptor LRP6.
2009,
Pubmed
,
Xenbase
Yanagawa,
Biochemical characterization of the Drosophila axin protein.
2000,
Pubmed
Zeng,
A dual-kinase mechanism for Wnt co-receptor phosphorylation and activation.
2005,
Pubmed
,
Xenbase
Zeng,
Initiation of Wnt signaling: control of Wnt coreceptor Lrp6 phosphorylation/activation via frizzled, dishevelled and axin functions.
2008,
Pubmed
,
Xenbase
