The novel catenin p120cas binds classical cadherins and induces an unusual morphological phenotype in NIH3T3 fibroblasts.

Reynolds AB, Daniel JM, Mo YY, Wu J, Zhang Z
Exp Cell Res. 1996 225 (2): 328-37

PMID: 8660921 · DOI:10.1006/excr.1996.0183

p120cas (CAS) is a tyrosine kinase substrate whose phosphorylation has been implicated in cell transformation by Src and in ligand-induced signaling through the EGF, PDGF, and CSF-1 receptors. More recently, CAS has been shown to associate with E-cadherin and its cofactors (catenins), molecules that are involved in cell adhesion. Although both CAS and beta-catenin contain armadillo repeat domains (Arm domains), the amino acid identity between these proteins in this region is only 22%, and it is not yet clear whether CAS will emulate other catenins by associating with other members of the cadherin family. Here we report that in addition to binding E-cadherin, wild-type CAS associated with N-cadherin and P-cadherin. Transient transfection of cloned CAS isoforms into MDCK epithelial cells indicated that CAS1 and CAS2 isoforms are equally capable of binding to E-cadherin even though these cells preferentially express CAS2 isoforms. In addition, CAS colocalized with N-cadherin in NIH3T3 cells and analysis of CAS mutants in vivo indicated that the CAS-N-cadherin interaction requires an intact CAS Arm domain. The data suggest that CAS-cadherin interactions in general are dictated by the conserved armadillo repeats and are not heavily influenced by sequences added outside the Arm domain by alternative splicing. Interestingly, overexpression of CAS in NIH3T3 cells induced a striking morphological phenotype characterized by the presence of long dendrite-like processes. This branching phenotype was specific for CAS, since (i) overexpression of the structurally similar beta-catenin had little effect on cell morphology, and (ii) the branching was abolished by deletions in the CAS Arm domain. Our data indicate that, like other catenins, CAS is a cofactor for multiple members of the cadherin family. However, the dramatically distinct phenotype exhibited by fibroblasts overexpressing CAS, versus beta-catenin, support recent data suggesting that these catenins have fundamentally different and possibly opposing roles in cadherin complexes.

MeSH Terms (19)

3T3 Cells Animals beta Catenin Cadherins Catenins Cell Adhesion Molecules Cell Size Cytoskeletal Proteins Dendrites DNA Gene Expression Mice Mutation Phenotype Phosphoproteins Protein Binding Protein Structure, Tertiary Repetitive Sequences, Nucleic Acid Trans-Activators

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