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GSK3B — LRP6

Pathways - manually collected, often from reviews:

• OpenBEL Selventa BEL large corpus: GSK3B → Complex of GSK3B-LRP6 (decreases, GSK3B/LRP6 Activity) Mi et al., J Biol Chem 2006*
  Evidence: Through a yeast two-hybrid screen, we identified the Wnt canonical pathway co-receptor protein low density lipoprotein receptor-related protein 6 (LRP6) as a GSK3-binding protein. The interaction between the C terminus of LRP6 and GSK3 was also confirmed by in vitro GST pull-down assays and in situ coimmunoprecipitation assays. In vitro assays using immunoprecipitated proteins demonstrated that the C terminus of LRP6 significantly attenuated the activity of GSK3beta
• OpenBEL Selventa BEL large corpus: GSK3B → LRP6 (decreases, LRP6 Activity) Mi et al., J Biol Chem 2006*
  Evidence: Through a yeast two-hybrid screen, we identified the Wnt canonical pathway co-receptor protein low density lipoprotein receptor-related protein 6 (LRP6) as a GSK3-binding protein. The interaction between the C terminus of LRP6 and GSK3 was also confirmed by in vitro GST pull-down assays and in situ coimmunoprecipitation assays. In vitro assays using immunoprecipitated proteins demonstrated that the C terminus of LRP6 significantly attenuated the activity of GSK3beta
• NCI Pathway Database Canonical Wnt signaling pathway: WNT3A/LRP6/FZD5/DVL complex (WNT3A-LRP6-FZD5-DVL3_DVL1_DVL2) → Axin1/GSK3 complex (AXIN1-GSK3B_GSK3A) (modification, collaborate)
  Zeng et al., Nature 2005, Bilic et al., Science 2007, Zeng et al., Development 2008
  Evidence: assay, physical interaction
• NCI Pathway Database Canonical Wnt signaling pathway: WNT3A/LRP6/FZD5/DVL complex (WNT3A-LRP6-FZD5-DVL3_DVL1_DVL2) → WNT3A/LRP6/FZD5/DVL/Axin1/GSK3 complex (WNT3A-LRP6-FZD5-DVL3_DVL1_DVL2-AXIN1-GSK3B_GSK3A) (modification, collaborate)
  Zeng et al., Nature 2005, Bilic et al., Science 2007, Zeng et al., Development 2008
  Evidence: assay, physical interaction
• NCI Pathway Database Canonical Wnt signaling pathway: Axin1/GSK3 complex (AXIN1-GSK3B_GSK3A) → WNT3A/LRP6/FZD5/DVL/Axin1/GSK3 complex (WNT3A-LRP6-FZD5-DVL3_DVL1_DVL2-AXIN1-GSK3B_GSK3A) (modification, collaborate)
  Zeng et al., Nature 2005, Bilic et al., Science 2007, Zeng et al., Development 2008
  Evidence: assay, physical interaction
• NCI Pathway Database Canonical Wnt signaling pathway: beta catenin (CTNNB1) → WNT3A/LRP6/FZD5/Axin1/GSK3 complex (WNT3A-LRP6-FZD5-AXIN1-GSK3B_GSK3A) (modification, collaborate)
  Kishida et al., Oncogene 1999, Amit et al., Genes Dev 2002, Cong et al., Mol Cell Biol 2004, Ikeda et al., EMBO J 1998
  Evidence: mutant phenotype
• NCI Pathway Database Canonical Wnt signaling pathway: APC (APC) → WNT3A/LRP6/FZD5/Axin1/GSK3 complex (WNT3A-LRP6-FZD5-AXIN1-GSK3B_GSK3A) (modification, collaborate)
  Kishida et al., Oncogene 1999, Amit et al., Genes Dev 2002, Cong et al., Mol Cell Biol 2004, Ikeda et al., EMBO J 1998
  Evidence: mutant phenotype
• NCI Pathway Database Canonical Wnt signaling pathway: Axin1/APC/GSK3/beta catenin complex (AXIN1-APC-GSK3B_GSK3A-CTNNB1) → WNT3A/LRP6/FZD5 complex (WNT3A-LRP6-FZD5) (modification, collaborate)
  Kishida et al., Oncogene 1999, Amit et al., Genes Dev 2002, Cong et al., Mol Cell Biol 2004, Ikeda et al., EMBO J 1998
  Evidence: mutant phenotype
• NCI Pathway Database Canonical Wnt signaling pathway: Axin1/APC/GSK3/beta catenin complex (AXIN1-APC-GSK3B_GSK3A-CTNNB1) → WNT3A/LRP6/FZD5/Axin1/GSK3 complex (WNT3A-LRP6-FZD5-AXIN1-GSK3B_GSK3A) (modification, collaborate)
  Kishida et al., Oncogene 1999, Amit et al., Genes Dev 2002, Cong et al., Mol Cell Biol 2004, Ikeda et al., EMBO J 1998
  Evidence: mutant phenotype
• NCI Pathway Database Canonical Wnt signaling pathway: WNT3A/LRP6/FZD5 complex (WNT3A-LRP6-FZD5) → WNT3A/LRP6/FZD5/Axin1/GSK3 complex (WNT3A-LRP6-FZD5-AXIN1-GSK3B_GSK3A) (modification, collaborate)
  Kishida et al., Oncogene 1999, Amit et al., Genes Dev 2002, Cong et al., Mol Cell Biol 2004, Ikeda et al., EMBO J 1998
  Evidence: mutant phenotype
• NCI Pathway Database Degradation of beta catenin: CK1 epsilon-CK1 delta-CK1 alpha (CSNK1E/CSNK1A1/CSNK1D) → WNT3A/LRP6/FZD5/DVL/Axin1/GSK3 complex (WNT3A-LRP6-FZD5-DVL3_DVL1_DVL2-AXIN1-GSK3B_GSK3A) (modification, activates)
  Kishida et al., Oncogene 1999, Kodama et al., J Biol Chem 1999, Amit et al., Genes Dev 2002, Cong et al., Mol Cell Biol 2004, Orford et al., J Biol Chem 1997, Ikeda et al., EMBO J 1998
  Evidence: mutant phenotype, assay, physical interaction
• NCI Pathway Database Canonical Wnt signaling pathway: WNT3A/LRP6/FZD5/DVL complex (WNT3A-LRP6-FZD5-DVL3_DVL1_DVL2) → Axin1/GSK3 complex (AXIN1-GSK3B_GSK3A) (modification, collaborate)
  Piao et al., PloS one 2008, Yum et al., Biochem Biophys Res Commun 2009
  Evidence: assay, physical interaction
• NCI Pathway Database Canonical Wnt signaling pathway: WNT3A/LRP6/FZD5/DVL complex (WNT3A-LRP6-FZD5-DVL3_DVL1_DVL2) → WNT3A/LRP6/FZD5/DVL/Axin1/GSK3 complex (WNT3A-LRP6-FZD5-DVL3_DVL1_DVL2-AXIN1-GSK3B_GSK3A) (modification, collaborate)
  Piao et al., PloS one 2008, Yum et al., Biochem Biophys Res Commun 2009
  Evidence: assay, physical interaction
• NCI Pathway Database Canonical Wnt signaling pathway: Axin1/GSK3 complex (AXIN1-GSK3B_GSK3A) → WNT3A/LRP6/FZD5/DVL/Axin1/GSK3 complex (WNT3A-LRP6-FZD5-DVL3_DVL1_DVL2-AXIN1-GSK3B_GSK3A) (modification, collaborate)
  Piao et al., PloS one 2008, Yum et al., Biochem Biophys Res Commun 2009
  Evidence: assay, physical interaction
• NCI Pathway Database Canonical Wnt signaling pathway: beta catenin (CTNNB1) → WNT3A/LRP6/FZD5/DVL/Axin1/GSK3/Axin1/GSK3 complex (WNT3A-LRP6-FZD5-DVL3_DVL1_DVL2-AXIN1-GSK3B_GSK3A) (modification, collaborate)
  Kishida et al., Oncogene 1999, Amit et al., Genes Dev 2002, Cong et al., Mol Cell Biol 2004, Ikeda et al., EMBO J 1998
  Evidence: mutant phenotype
• NCI Pathway Database Canonical Wnt signaling pathway: beta catenin (CTNNB1) → WNT3A/LRP6/FZD5/DVL/Axin1/GSK3 complex (WNT3A-LRP6-FZD5-DVL3_DVL1_DVL2-AXIN1-GSK3B_GSK3A) (modification, collaborate)
  Kishida et al., Oncogene 1999, Amit et al., Genes Dev 2002, Cong et al., Mol Cell Biol 2004, Ikeda et al., EMBO J 1998
  Evidence: mutant phenotype
• NCI Pathway Database Canonical Wnt signaling pathway: APC (APC) → WNT3A/LRP6/FZD5/DVL/Axin1/GSK3/Axin1/GSK3 complex (WNT3A-LRP6-FZD5-DVL3_DVL1_DVL2-AXIN1-GSK3B_GSK3A) (modification, collaborate)
  Kishida et al., Oncogene 1999, Amit et al., Genes Dev 2002, Cong et al., Mol Cell Biol 2004, Ikeda et al., EMBO J 1998
  Evidence: mutant phenotype
• NCI Pathway Database Canonical Wnt signaling pathway: APC (APC) → WNT3A/LRP6/FZD5/DVL/Axin1/GSK3 complex (WNT3A-LRP6-FZD5-DVL3_DVL1_DVL2-AXIN1-GSK3B_GSK3A) (modification, collaborate)
  Kishida et al., Oncogene 1999, Amit et al., Genes Dev 2002, Cong et al., Mol Cell Biol 2004, Ikeda et al., EMBO J 1998
  Evidence: mutant phenotype
• NCI Pathway Database Canonical Wnt signaling pathway: Axin1/APC/GSK3/beta catenin complex (AXIN1-APC-GSK3B_GSK3A-CTNNB1) → WNT3A/LRP6/FZD5/DVL/Axin1/GSK3/Axin1/GSK3 complex (WNT3A-LRP6-FZD5-DVL3_DVL1_DVL2-AXIN1-GSK3B_GSK3A) (modification, collaborate)
  Kishida et al., Oncogene 1999, Amit et al., Genes Dev 2002, Cong et al., Mol Cell Biol 2004, Ikeda et al., EMBO J 1998
  Evidence: mutant phenotype
• NCI Pathway Database Canonical Wnt signaling pathway: Axin1/APC/GSK3/beta catenin complex (AXIN1-APC-GSK3B_GSK3A-CTNNB1) → WNT3A/LRP6/FZD5/DVL/Axin1/GSK3 complex (WNT3A-LRP6-FZD5-DVL3_DVL1_DVL2-AXIN1-GSK3B_GSK3A) (modification, collaborate)
  Kishida et al., Oncogene 1999, Amit et al., Genes Dev 2002, Cong et al., Mol Cell Biol 2004, Ikeda et al., EMBO J 1998
  Evidence: mutant phenotype
• NCI Pathway Database Canonical Wnt signaling pathway: WNT3A/LRP6/FZD5/DVL/Axin1/GSK3/Axin1/GSK3 complex (WNT3A-LRP6-FZD5-DVL3_DVL1_DVL2-AXIN1-GSK3B_GSK3A) → WNT3A/LRP6/FZD5/DVL/Axin1/GSK3 complex (WNT3A-LRP6-FZD5-DVL3_DVL1_DVL2-AXIN1-GSK3B_GSK3A) (modification, collaborate)
  Kishida et al., Oncogene 1999, Amit et al., Genes Dev 2002, Cong et al., Mol Cell Biol 2004, Ikeda et al., EMBO J 1998
  Evidence: mutant phenotype
• NCI Pathway Database Canonical Wnt signaling pathway: CK1 gamma (CSNK1G1) → WNT3A/LRP6/FZD5/DVL/Axin1/GSK3 complex (WNT3A-LRP6-FZD5-DVL3_DVL1_DVL2-AXIN1-GSK3B_GSK3A) (modification, activates)
  Davidson et al., Nature 2005, Zeng et al., Nature 2005, Zeng et al., Development 2008
  Evidence: assay, physical interaction
• NCI Pathway Database Canonical Wnt signaling pathway: CK1 gamma (CSNK1G1) → WNT3A/LRP6/FZD5/DVL/Axin1/GSK3 complex (WNT3A-LRP6-FZD5-DVL3_DVL1_DVL2-AXIN1-GSK3B_GSK3A) (modification, activates)
  Zeng et al., Nature 2005, Piao et al., PloS one 2008, Yum et al., Biochem Biophys Res Commun 2009
  Evidence: assay, physical interaction
• NCI Pathway Database Canonical Wnt signaling pathway: WNT3A/LRP6/FZD5/DVL complex (WNT3A-LRP6-FZD5-DVL3_DVL1_DVL2) → Axin1/APC/GSK3/beta catenin complex (AXIN1-APC-GSK3B_GSK3A-CTNNB1) (modification, collaborate)
  Kishida et al., Oncogene 1999, Amit et al., Genes Dev 2002, Cong et al., Mol Cell Biol 2004, Ikeda et al., EMBO J 1998
  Evidence: mutant phenotype
• NCI Pathway Database Canonical Wnt signaling pathway: WNT3A/LRP6/FZD5/DVL complex (WNT3A-LRP6-FZD5-DVL3_DVL1_DVL2) → WNT3A/LRP6/FZD5/DVL/Axin1/GSK3 complex (WNT3A-LRP6-FZD5-DVL3_DVL1_DVL2-AXIN1-GSK3B_GSK3A) (modification, collaborate)
  Kishida et al., Oncogene 1999, Amit et al., Genes Dev 2002, Cong et al., Mol Cell Biol 2004, Ikeda et al., EMBO J 1998
  Evidence: mutant phenotype
• NCI Pathway Database Canonical Wnt signaling pathway: APC (APC) → WNT3A/LRP6/FZD5/DVL/Axin1/GSK3 complex (WNT3A-LRP6-FZD5-DVL3_DVL1_DVL2-AXIN1-GSK3B_GSK3A) (modification, collaborate)
  Kishida et al., Oncogene 1999, Amit et al., Genes Dev 2002, Cong et al., Mol Cell Biol 2004, Ikeda et al., EMBO J 1998
  Evidence: mutant phenotype
• NCI Pathway Database Canonical Wnt signaling pathway: beta catenin (CTNNB1) → WNT3A/LRP6/FZD5/DVL/Axin1/GSK3 complex (WNT3A-LRP6-FZD5-DVL3_DVL1_DVL2-AXIN1-GSK3B_GSK3A) (modification, collaborate)
  Kishida et al., Oncogene 1999, Amit et al., Genes Dev 2002, Cong et al., Mol Cell Biol 2004, Ikeda et al., EMBO J 1998
  Evidence: mutant phenotype
• NCI Pathway Database Canonical Wnt signaling pathway: Axin1/APC/GSK3/beta catenin complex (AXIN1-APC-GSK3B_GSK3A-CTNNB1) → WNT3A/LRP6/FZD5/DVL/Axin1/GSK3 complex (WNT3A-LRP6-FZD5-DVL3_DVL1_DVL2-AXIN1-GSK3B_GSK3A) (modification, collaborate)
  Kishida et al., Oncogene 1999, Amit et al., Genes Dev 2002, Cong et al., Mol Cell Biol 2004, Ikeda et al., EMBO J 1998
  Evidence: mutant phenotype
• Reactome Reaction: LRP6 → GSK3B (reaction) Mao et al., Mol Cell 2001, Tamai et al., Mol Cell 2004, He et al., Development 2004, Zeng et al., Nature 2005, Schwarz-Romond et al., Nature structural & molecular biology 2007, Bilic et al., Science 2007, Zeng et al., Development 2008, MacDonald et al., J Biol Chem 2008
• Reactome Reaction: LRP6 → GSK3B (indirect_complex) Mao et al., Mol Cell 2001, Tamai et al., Mol Cell 2004, He et al., Development 2004, Davidson et al., Nature 2005, Zeng et al., Nature 2005, Yamamoto et al., Dev Cell 2006, Schwarz-Romond et al., Nature structural & molecular biology 2007, Bilic et al., Science 2007, Zeng et al., Development 2008, MacDonald et al., J Biol Chem 2008, Yamamoto et al., Dev Cell 2008

Protein-Protein interactions - manually collected from original source literature:

Studies that report less than 10 interactions are marked with *

• IRef Biogrid Interaction: LRP6 — GSK3B (physical association, affinity chromatography technology) Yamamoto et al., Dev Cell 2006
• IRef Biogrid Interaction: LRP6 — GSK3B (direct interaction, enzymatic study) Piao et al., PloS one 2008
• IRef Biogrid Interaction: LRP6 — GSK3B (direct interaction, far western blotting) Piao et al., PloS one 2008
• IRef Intact Interaction: Complex of 19 proteins (association, anti bait coimmunoprecipitation) Li et al., Cell 2012
• IRef Intact Interaction: Complex of CAV1-GSK3B-LRP6-CTNNB1-LRP6-CTNNB1-CAV1-GSK3B (physical association, anti tag coimmunoprecipitation) Yamamoto et al., Dev Cell 2006
• IRef Intact Interaction: LRP6 — GSK3B (physical association, pull down) Mi et al., J Biol Chem 2006*
• IRef Intact Interaction: LRP6 — GSK3B (physical association, anti tag coimmunoprecipitation) Mi et al., J Biol Chem 2006*
• IRef Intact Interaction: Complex of CTNNB1-GSK3B-LRP6-LRP6-GSK3B-CTNNB1 (physical association, anti tag coimmunoprecipitation) Yamamoto et al., Dev Cell 2006

Text-mined interactions from Literome

Piao et al., PloS one 2008 : These observations demonstrate that phosphorylated LRP6/5 both recruits and directly inhibits GSK3beta using two distinct portions of its cytoplasmic sequence, and suggest a novel mechanism of activation in this signaling pathway
Beagle et al., J Cell Biochem 2009 : Previously, we showed that the free LRP6 intracellular domain (LRP6-ICD) can activate the Wnt/beta-catenin pathway in a beta-catenin and TCF/LEF-1 dependent manner, as well as interact with and attenuate GSK3beta activity ... LRP6-ICD and a mutant in which all 5 PPP ( S/T ) P motifs were changed to PPP ( A ) P motifs equivalently interacted with and attenuated GSK3beta activity in vitro, and both constructs inhibited the in situ GSK3beta mediated phosphorylation of beta-catenin and tau to the same extent ... These data indicate that the LRP6-ICD attenuates GSK3beta activity similar to other GSK3beta binding proteins, and is not a result of it being a GSK3beta substrate