Activation of TrkA tyrosine kinase in embryonal carcinoma cells promotes cell compaction, independently of tyrosine phosphorylation of catenins

Cadherins are transmembrane receptors whose extracellular domain mediates h omophilic cell-cell interactions, while their cytoplasmic domain associates with a family of proteins known as catenins. Although the mechanisms that regulate the assembly and functional state of cadherin-catenin complexes ar e poorly understood, current evidence supports a role for protein tyrosine kinase activity in regulating cell adhesion and migration. Tyrosine phospho rylation of catenins is thought to mediate loss of intercellular adhesion p romoted by activation of receptor tyrosine kinases in epithelial cells. Her e, we show that activation of ectopically expressed TrkA, the tyrosine kina se receptor for nerve growth factor (NGF), stimulates embryonal carcinoma P 19 cells to develop extensive intercellular contacts and to assemble into c losely packed clusters. Thus, activation of receptor tyrosine kinases can d ifferentially regulate adhesiveness by cell-type-specific mechanisms. Furth ermore, activation of TrkA in P19 and epithelial MDCK cells induces tyrosin e phosphorylation of p120(ctn) and of beta-catenin, irrespective of the eli cited cellular response. The selective Src tyrosine kinase inhibitor PP2, h owever, suppresses NGF- or HGF-induced tyrosine phosphorylation of catenins in both P19 and MDCK cells without interfering with the acquisition of a c ompacted or scattered phenotype. These findings provide a cogent argument f or considering that tyrosine phosphorylation of catenins is dispensable for their interaction with cadherins and, ultimately, for the modulation of ca dherin-based cell adhesion by receptor tyrosine kinases.