The disruption of adherens junctions is associated with a decrease of E-cadherin phosphorylation by protein kinase CK2.

The down-regulation of E-cadherin is a common event in carcinogenesis. Phosphorylation/dephosphorylation is one posttranscriptional process which may regulate intercellular junctions. Here we show that in okadaic acid-treated keratinocytes, E-cadherin expression is shifted from the membrane to the cytoplasm, preventing cells from forming aggregates.

Brachyury is a target gene of the Wnt/beta-catenin signaling pathway.

To identify target genes of the Wnt/beta-catenin signaling pathway in early mouse embryonic development we have established a co-culture system consisting of NIH3T3 fibroblasts expressing different Wnts as feeder layer cells and embryonic stem (ES) cells expressing a green fluorescent protein (GFP) reporter gene transcriptionally regulated by the TCF/beta-catenin complex. ES cells specifically respond to Wnt signal as monitored by GFP expression. In GFP-positive ES cells we observe expression of Brachyury.

Casein kinase II phosphorylation of E-cadherin increases E-cadherin/beta-catenin interaction and strengthens cell-cell adhesion.

Beta-catenin, a member of the Armadillo repeat protein family, binds directly to the cytoplasmic domain of E-cadherin, linking it via alpha-catenin to the actin cytoskeleton. A 30-amino acid region within the cytoplasmic domain of E-cadherin, conserved among all classical cadherins, has been shown to be essential for beta-catenin binding. This region harbors several putative casein kinase II (CKII) and glycogen synthase kinase-3beta (GSK-3beta) phosphorylation sites and is highly phosphorylated.

Modification of the E-cadherin-catenin complex in mitotic Madin-Darby canine kidney epithelial cells.

One of the hallmarks of polarized epithelial cells undergoing mitosis is their rounded morphology. This phenotype correlates with a reduced cell-substratum adhesion, apparently caused by a modulation of integrin function. However, it is still unclear whether the cadherin-mediated cell-cell adhesion is affected as well.

beta-catenin is a target for the ubiquitin-proteasome pathway.

beta-catenin is a central component of the cadherin cell adhesion complex and plays an essential role in the Wingless/Wnt signaling pathway. In the current model of this pathway, the amount of beta-catenin (or its invertebrate homolog Armadillo) is tightly regulated and its steady-state level outside the cadherin-catenin complex is low in the absence of Wingless/Wnt signal. Here we show that the ubiquitin-dependent proteolysis system is involved in the regulation of beta-catenin turnover.

Genetic and biochemical dissection of protein linkages in the cadherin-catenin complex.

The cadherin-catenin complex is important for mediating homotypic, calcium-dependent cell-cell interactions in diverse tissue types. Although proteins of this complex have been identified, little is known about their interactions. Using a genetic assay in yeast and an in vitro protein-binding assay, we demonstrate that beta-catenin is the linker protein between E-cadherin and alpha-catenin and that E-cadherin does not bind directly to alpha-catenin.

Assembly of the cadherin-catenin complex in vitro with recombinant proteins.

The cytoplasmic domain of classical cadherins is tightly associated with three proteins termed alpha-, beta- and gamma-catenin. These accessory proteins are of central importance for the adhesive properties of this class of cell adhesion molecules. In order to examine the molecular architecture of the cadherin-catenin complex in more detail we have expressed the catenins and the cytoplasmic domain of E-cadherin as fusion proteins in Escherichia coli, and analyzed the interaction of purified recombinant cadherin and catenins in combinatorial protein-protein interaction experiments.

A short core region of E-cadherin is essential for catenin binding and is highly phosphorylated.

Classical cadherins associate with three cytoplasmic proteins, termed alpha, -beta- and gamma-catenin. This association mediates the attachment of cadherins to the microfilament network, which is believed to be of major importance for cadherin function. Deletion of the carboxyterminal 72-amino acid residues of E-cadherin had been previously shown to prevent catenin binding.

Intracellular associations of adhesion molecules.

Significant advances have recently been made in our understanding of the cytoplasmic anchorage of adhesion molecules. The identification of catenins, a new class of proteins involved in the cytoplasmic anchorage of cadherins that are structurally homologous to other peripheral cytoplasmic proteins, emphasizes the existence of protein families that modulate the function of cell-substrate and cell-cell adhesion molecules.