title: Independent interactions of phosphorylated β-catenin with E-cadherin at cell-cell contacts and APC at cell protrusions.
abstract: BACKGROUND
  The APC tumour suppressor functions in several cellular processes including the regulation of β-catenin in Wnt signalling and in cell adhesion and migration.
  
  
  RESULTS
  In this study, we establish that in epithelial cells N-terminally phosphorylated β-catenin specifically localises to several subcellular sites including cell-cell contacts and the ends of cell protrusions. N-terminally phosphorylated β-catenin associates with E-cadherin at adherens junctions and with APC in cell protrusions. We isolated APC-rich protrusions from stimulated cells and detected β-catenin, GSK3β and CK1α, but not axin. The APC/phospho-β-catenin complex in cell protrusions appears to be distinct from the APC/axin/β-catenin destruction complex. GSK3β phosphorylates the APC-associated population of β-catenin, but not the cell junction population. β-catenin associated with APC is rapidly phosphorylated and dephosphorylated. HGF and wound-induced cell migration promote the localised accumulation of APC and phosphorylated β-catenin at the leading edge of migrating cells. APC siRNA and analysis of colon cancer cell lines show that functional APC is required for localised phospho-β-catenin accumulation in cell protrusions.
  
  
  CONCLUSIONS
  We conclude that N-terminal phosphorylation of β-catenin does not necessarily lead to its degradation but instead marks distinct functions, such as cell migration and/or adhesion processes. Localised regulation of APC-phospho-β-catenin complexes may contribute to the tumour suppressor activity of APC.
authors.affiliation: Ludwig Institute for Cancer Research, Melbourne, Victoria, Australia. Maree.faux@ludwig.edu.au
authors.forename: Maree C
authors.initials: MC
authors.lastname: Faux
authors.forename: Janine L
authors.initials: JL
authors.lastname: Coates
authors.forename: Nadia J
authors.initials: NJ
authors.lastname: Kershaw
authors.forename: Meredith J
authors.initials: MJ
authors.lastname: Layton
authors.forename: Antony W
authors.initials: AW
authors.lastname: Burgess
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D047389:Casein Kinase I / Q000378:metabolism; D002448:Cell Adhesion; D002460:Cell Line; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D004285:Dogs; D004847:Epithelial Cells / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D045325:HCT116 Cells; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D007365:Intercellular Junctions / Q000378:metabolism*; D018613:Microscopy, Confocal; D008870:Microtubules / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D011554:Pseudopodia / Q000378:metabolism; D034622:RNA Interference; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D015820:Cadherins; D051176:beta Catenin; D017228:Hepatocyte Growth Factor; D047389:Casein Kinase I; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3