For a correct differentiation of epithelial cells proper cell-to-cell contacts need to be established. The adhesion junction protein e-cadherin plays a critical role in this process. E-cadherin function is controlled by associated proteins named catenins (ß, a, ? and p120) which link E-cadherin to the actin cytoskeleton. The control of E-cadherin function is relevant for its effects in epithelial tumors cells. This project is focussed on the regulation of adhesion junctions and desmosomes. Specifically, we want to analyze the regulation of E-cadherin function by covalent modifications (phosphorylation) in itself or in the bound catenins. Thus, our current specific goals are headed to; a) compare plakoglobin and ß-catenin functions, analysing whether the kinases which specifically phosphorylate these proteins in equivalent residues, induce or not similar effects, and to determine whether plakoglobin phosphorylation is responsible of its switch from desmosomes to adherent junctions. Taking into account the data on ß-catetin structure published by our group, we plan also to anlyxe how ß-catetin and plakoglobin phosphorylation affects the interaction with other partners involved in its role as a transcriptional coactivator (ß-catetin) or as an inhibitor (plakoglobin); b) identify the exact role of p120-catenin in adherens junctions, especially its possible regulatory function coupling kinases to the adhesion complex (as suggested by our preliminary results), its effect on the regulation of E-cadherin function and d) characterize the moleculr basis of the effect of N-cadherin on the lost of adhesion in epithelial cells and try explain why N-cadherin expression in epithelial cells induces invasion and a lost of E-cadherin expression
|Effective start/end date||1/12/03 → 30/11/06|
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