Interaction of lp-dlg/KIAA0583, a membrane-associated guanylate kinase family protein, with vinexin and beta-catenin at sites of cell-cell contact.

Vinexin is a recently identified cytoskeletal protein and plays a key role in the regulation of cytoskeletal organization and signal transduction. Vinexin localizes at sites of cell-extracellular matrix adhesion in NIH3T3 fibroblasts and at sites of cell-cell contact in epithelial LLC-PK1 cells. Expression of vinexin promotes the formation of actin ...
stress fiber, but the role of vinexin at sites of cell-cell contact is unclear. Here we identified lp-dlg/KIAA0583 as a novel binding partner for vinexin by using yeast two-hybrid screening. lp-dlg/KIAA0583 has a NH2-terminal coiled-coil-like domain, in addition to four PDZ domains, an Src homology (SH) 3 domain, and a guanylate kinase domain, which are conserved structures in membrane-associated guanylate kinase family proteins. The third SH3 domain of vinexin bound to the region between the second and third PDZ domain of lp-dlg, which contains a proline-rich sequence. lp-dlg colocalized with vinexin at sites of cell-cell contact in LLC-PK1 cells. Furthermore, lp-dlg colocalized with beta-catenin, a major adherens junction protein, in LLC-PK1 cells. Co-immunoprecipitation experiments revealed that both endogenous and epitope-tagged deletion mutants of lp-dlg/KIAA0583 associated with beta-catenin. We also showed that these three proteins could form a ternary complex. Together these findings suggest that lp-dlg/KIAA0583 is a novel scaffolding protein that can link the vinexin-vinculin complex and beta-catenin at sites of cell-cell contact.
Mesh Terms:
3T3 Cells, Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Animals, Blotting, Northern, COS Cells, Cell Communication, Cell Line, Cell Membrane, Cloning, Molecular, Cytoskeletal Proteins, DNA, Complementary, Epithelial Cells, Gene Deletion, Genes, Tumor Suppressor, Glutathione Transferase, Guanylate Kinase, Humans, Membrane Proteins, Mice, Models, Genetic, Molecular Sequence Data, Muscle Proteins, Nucleoside-Phosphate Kinase, Polymerase Chain Reaction, Precipitin Tests, Protein Binding, Protein Structure, Tertiary, Proteins, Recombinant Fusion Proteins, Tissue Distribution, Trans-Activators, Tumor Suppressor Proteins, Two-Hybrid System Techniques, beta Catenin, src Homology Domains
J. Biol. Chem.
Date: Jun. 13, 2003
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