Independent interactions of phosphorylated ?-catenin with E-cadherin at cell-cell contacts and APC at cell protrusions.

ABSTRACT: The APC tumour suppressor functions in several cellular processes including the regulation of ?-catenin in Wnt signalling and in cell adhesion and migration.In this study, we establish that in epithelial cells N-terminally phosphorylated ?-catenin specifically localises to several subcellular sites including cell-cell contacts and the ends of cell protrusions. N-terminally phosphorylated ?-catenin associates with E-cadherin at adherens junctions and with APC in cell protrusions. We isolated APC-rich protrusions from stimulated cells and detected ?-catenin, GSK3? and CK1?, but not axin. The APC/phospho-?-catenin complex in cell protrusions appears to be distinct from the APC/axin/?-catenin destruction complex. GSK3? phosphorylates the APC-associated population of ?-catenin, but not the cell junction population. ?-catenin associated with APC is rapidly phosphorylated and dephosphorylated. HGF and wound-induced cell migration promote the localised accumulation of APC and phosphorylated ?-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-?-catenin accumulation in cell protrusions.We conclude that N-terminal phosphorylation of ?-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-?-catenin complexes may contribute to the tumour suppressor activity of APC.

SUBMITTER: Faux MC 

PROVIDER: S-EPMC2994709 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature