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APC — GSK3B

Pathways - manually collected, often from reviews:

• KEGG Endometrial cancer: Complex of APC-APC2-AXIN1-AXIN2-GSK3B → CTNNB1 (protein-protein, missing interaction)
• NCI Pathway Database Degradation of beta catenin: Axin1/APC//beta catenin/GSK3 complex (AXIN1-APC-CTNNB1-GSK3B_GSK3A) → GSK3 (GSK3B/GSK3A) (modification, collaborate) 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: assay, physical interaction
• NCI Pathway Database Degradation of beta catenin: Axin1/APC//beta catenin/GSK3 complex (AXIN1-APC-CTNNB1-GSK3B_GSK3A) → Axin1/APC//beta catenin complex (AXIN1-APC-CTNNB1) (modification, collaborate)
  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: assay, physical interaction
• NCI Pathway Database Degradation of beta catenin: GSK3 (GSK3B/GSK3A) → Axin1/APC//beta catenin complex (AXIN1-APC-CTNNB1) (modification, collaborate)
  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: assay, physical interaction
• NCI Pathway Database Canonical Wnt signaling pathway: beta catenin (CTNNB1) → 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: APC (APC) → 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: 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 Degradation of beta catenin: APC/beta catenin complex (APC-CTNNB1) → Axin2/APC/GSK3/beta catenin complex (AXIN2-APC-GSK3B_GSK3A-CTNNB1) (modification, collaborate)
  Liu et al., Curr Biol 2005, Behrens et al., Science 1998, Yamamoto et al., Mol Cell Biol 1998
  Evidence: assay, physical interaction
• NCI Pathway Database Degradation of beta catenin: APC/beta catenin complex (APC-CTNNB1) → Axin2/GSK3 complex (AXIN2-GSK3B_GSK3A) (modification, collaborate)
  Liu et al., Curr Biol 2005, Behrens et al., Science 1998, Yamamoto et al., Mol Cell Biol 1998
  Evidence: assay, physical interaction
• NCI Pathway Database Degradation of beta catenin: Axin2/APC/GSK3/beta catenin complex (AXIN2-APC-GSK3B_GSK3A-CTNNB1) → Axin2/GSK3 complex (AXIN2-GSK3B_GSK3A) (modification, collaborate)
  Liu et al., Curr Biol 2005, Behrens et al., Science 1998, Yamamoto et al., Mol Cell Biol 1998
  Evidence: assay, physical interaction
• NCI Pathway Database Canonical Wnt signaling pathway: PP2A B56alpha (PPP2R5A) → Axin1/APC/GSK3/beta catenin complex (AXIN1-APC-GSK3B_GSK3A-CTNNB1) (modification, activates)
  Staal et al., EMBO Rep 2002, Zhang et al., J Biol Chem 2009
  Evidence: assay, physical interaction
• NCI Pathway Database Canonical Wnt signaling pathway: beta catenin (CTNNB1) → Axin1/APC/GSK3/beta catenin complex (AXIN1-APC-GSK3B_GSK3A-CTNNB1) (modification, collaborate)
  Staal et al., EMBO Rep 2002, Zhang et al., J Biol Chem 2009
  Evidence: assay, physical interaction
• NCI Pathway Database Presenilin action in Notch and Wnt signaling: Gsk3beta (GSK3B) → Axin1/APC//beta catenin complex (AXIN1-APC-CTNNB1) (modification, activates)
  Ha et al., Mol Cell 2004
  Evidence: assay, other species
• NCI Pathway Database Presenilin action in Notch and Wnt signaling: Gsk3beta (GSK3B) → APC (APC) (modification, activates) Ha et al., Mol Cell 2004
  Evidence: assay, other species
• NCI Pathway Database Degradation of beta catenin: APC/beta catenin complex (APC-CTNNB1) → Axin1/APC/GSK3/beta catenin complex (AXIN1-APC-GSK3B_GSK3A-CTNNB1) (modification, collaborate)
  Yamamoto et al., J Biol Chem 1999, Willert et al., Genes Dev 1999, Farr et al., J Cell Biol 2000, van Noort et al., J Biol Chem 2002, Dajani et al., EMBO J 2003, Ha et al., Mol Cell 2004, Liu et al., Curr Biol 2005, Su et al., Mol Cell 2008
  Evidence: assay
• NCI Pathway Database Degradation of beta catenin: APC/beta catenin complex (APC-CTNNB1) → Axin1/GSK3 complex (AXIN1-GSK3B_GSK3A) (modification, collaborate)
  Yamamoto et al., J Biol Chem 1999, Willert et al., Genes Dev 1999, Farr et al., J Cell Biol 2000, van Noort et al., J Biol Chem 2002, Dajani et al., EMBO J 2003, Ha et al., Mol Cell 2004, Liu et al., Curr Biol 2005, Su et al., Mol Cell 2008
  Evidence: assay
• NCI Pathway Database Degradation of beta catenin: Axin1/APC/GSK3/beta catenin complex (AXIN1-APC-GSK3B_GSK3A-CTNNB1) → Axin1/GSK3 complex (AXIN1-GSK3B_GSK3A) (modification, collaborate)
  Yamamoto et al., J Biol Chem 1999, Willert et al., Genes Dev 1999, Farr et al., J Cell Biol 2000, van Noort et al., J Biol Chem 2002, Dajani et al., EMBO J 2003, Ha et al., Mol Cell 2004, Liu et al., Curr Biol 2005, Su et al., Mol Cell 2008
  Evidence: assay
• NCI Pathway Database Canonical Wnt signaling pathway: beta catenin (CTNNB1) → 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: APC (APC) → 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: 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 Presenilin action in Notch and Wnt signaling: Gsk3beta (GSK3B) → Axin1/APC//beta catenin complex (AXIN1-APC-CTNNB1) (modification, activates)
  Dajani et al., EMBO J 2003
• NCI Pathway Database Presenilin action in Notch and Wnt signaling: Gsk3beta (GSK3B) → APC (APC) (modification, activates) Dajani et al., EMBO J 2003
• NCI Pathway Database CDC42 signaling events: Gsk3beta (GSK3B) → APC (APC) (modification, activates) Etienne-Manneville et al., Nature 2003*
  Evidence: assay
• NCI Pathway Database Degradation of beta catenin: Axin1/APC//beta catenin/GSK3 complex (AXIN1-APC-CTNNB1-GSK3B_GSK3A) → Axin1/APC/GSK3/beta catenin complex (AXIN1-APC-GSK3B_GSK3A-CTNNB1) (modification, collaborate)
  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: assay
• 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: APC (APC) → 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: 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) → 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: 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: APC → GSK3B (direct_complex) Seeling et al., Science 1999, Yamamoto et al., J Biol Chem 1999, Willert et al., Genes Dev 1999, Jho et al., Biochem Biophys Res Commun 1999, Dajani et al., EMBO J 2003, Xing et al., Mol Cell 2004, Liu et al., J Mol Biol 2006, Luo et al., EMBO J 2007, Major et al., Science 2007, Hanaki et al., Mol Cancer Ther 2012, Saito-Diaz et al., Growth Factors 2013, Kim et al., Science 2013, Ikeda et al., EMBO J 1998
• Reactome Reaction: APC → GSK3B (reaction) Seeling et al., Science 1999, Yamamoto et al., J Biol Chem 1999, Willert et al., Genes Dev 1999, Jho et al., Biochem Biophys Res Commun 1999, Liu et al., Cell 2002, Amit et al., Genes Dev 2002, Dajani et al., EMBO J 2003, Liu et al., J Mol Biol 2006, Luo et al., EMBO J 2007, Major et al., Science 2007, Schwarz-Romond et al., Nature structural & molecular biology 2007, Bilic et al., Science 2007, Huang et al., Curr Opin Cell Biol 2008, Piao et al., PloS one 2008, Niehrs et al., Cell 2010, Taelman et al., Cell 2010, Schuldt et al., Nat Rev Mol Cell Biol 2011, Hanaki et al., Mol Cancer Ther 2012, Saito-Diaz et al., Growth Factors 2013, Kim et al., Science 2013, Ikeda et al., EMBO J 1998
• WikiPathways Regulation of Wnt/B-catenin Signaling by Small Molecule Compounds: DVL2 → Complex of AXIN1-TNKS-GSK3B-APC-CSNK1A1-CTNNB1 (activation)
  
• WikiPathways Wnt/beta-catenin Signaling Pathway in Leukemia: AKT1 → Complex of AXIN2-APC-CSNK1A1-GSK3B (mim-stimulation)
  
• WikiPathways Copper homeostasis: GSK3B → APC (activation)
• WikiPathways DNA Damage Response (only ATM dependent): Complex of GSK3B-APC → CDKN1A (activation)

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

Studies that report less than 10 interactions are marked with *

• IRef Biogrid Interaction: GSK3B — APC (physical association, affinity chromatography technology) Davies et al., Int J Oncol 2001*
• MIPS CORUM AXIN-APC-betaCatenin-GSK3B complex: AXIN-APC-betaCatenin-GSK3B complex complex (APC-AXIN1-CTNNB1-GSK3B) Hinoi et al., J Biol Chem 2000*
• IRef Innatedb Interaction: Complex of CTNNB1-APC-GSK3B-GSK3B-CTNNB1-APC (unknown, -) Rubinfeld et al., Science 1996
• IRef Innatedb Interaction: APC — GSK3B (unknown, -) Rubinfeld et al., Science 1996
• IRef Intact Interaction: Complex of DVL3-GSK3B-AXIN1-APC (association, anti bait coimmunoprecipitation) Li et al., Cell 2012
• IRef Intact Interaction: Complex of GSK3B-AXIN1-CTNNB1-AMER1-APC (association, anti bait coimmunoprecipitation) Li et al., Cell 2012
• IRef Intact Interaction: Complex of 19 proteins (association, anti bait coimmunoprecipitation) Li et al., Cell 2012
• IRef Intact Interaction: Complex of 12 proteins (association, tandem affinity purification) Varjosalo et al., Cell reports 2013
• IRef Intact Interaction: Complex of 120 proteins (association, anti bait coimmunoprecipitation) Brazão et al., FEBS Lett 2012
• IRef Intact Interaction: Complex of 25 proteins (association, anti bait coimmunoprecipitation) Li et al., Cell 2012

Text-mined interactions from Literome

Ikeda et al., Oncogene 2000 : GSK-3beta dependent phosphorylation of APC- ( 1211-2075 ) which has the Axin binding site was facilitated by Axin, but that of APC- ( 959-1338 ) which lacks the Axin binding site was not ... Axin- ( 298-506 ) or Axin- ( 298-832 ), which has the GSK-3beta- and beta-catenin- but not APC binding sites, did not enhance GSK-3beta dependent phosphorylation of either APC- ( 1211-2075 ) or APC- ( 959-1338 ) ... Taken together, these results suggest that GSK-3beta dependent phosphorylation of APC can be modulated by beta-catenin and PP2A complexed with Axin
Gärtner et al., J Cell Sci 2006 : Finally, the adenomatous polyposis coli (APC) protein accumulates at the tip of one neurite before and during axon elongation, but global inhibition of GSK-3beta leads to APC protein accumulation in all neurites
Rao et al., Oncogene 2008 (Adenomatous Polyposis Coli) : There have been conflicting reports on the requirement of GSK-3beta mediated phosphorylation of the tumor suppressor adenomatous polyposis coli (APC) vis-à-vis its ability to bind and degrade beta-catenin
Yang et al., Proc Natl Acad Sci U S A 2009 : APC also induced phosphorylation of Ser-9 in glycogen synthase kinase 3beta ( GSK3beta ), which was blocked by the PI3K inhibitor LY294002 ... Receptor associated protein (RAP), a general antagonist for binding of ligands to LDL receptor family members, inhibited APC induced phosphorylation of Dab1 and GSK3beta , whereas anti-EPCR or anti-PAR1 blocking antibodies did not
Wang et al., Clin Colorectal Cancer 2011 (Adenocarcinoma...) : Though APC and CTNNB1 regulation by GSK3B are frequently disrupted by mutations in colon cancers, our observations suggest that increased functional GSK3B might drive other growth promoting signals in colorectal tumorigenesis