Augmentation of Adherens Junction Formation in Mesenchymal Cells by Co-expression of N-CAM or Short-term Stimulation of Tyrosine-phosphorylation

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Abstract
Adherens-type junctions (AJ) are specialized intercellular contacts, mediated by cadherins and characterized by the association with actin filaments through a vinculin-and cateninrich submembrane plaque. We describe here two mechanisms which potentiate AJ formation in mesenchymal cells. These include the augmentation of AJ by the co-expression of another adhesion molecule, namely NCAM, and the stimulation of tyrosine phosphorylation. These effects were obtained in NIH-3T3 cells, which, under normal conditions, have poor cadherin-and vinculin-containing intercellular junctions. The transfection of these cells with cDNA encoding the 140kD NCAM resulted in the extensive formation of cadherin-and vinculin-rich AJ, demonstrating a cooperativity between the two junctional systems. AJ could also be induced in 3T3, and in CEF and COS cells, upon a brief exposure to H2O2/vanadate, which elevates cellular levels of phosphotyrosine due to inhibition of tyrosine-specific phosphatases. This induction was, however, transient since prolonged exposure to H2O2/vanadate resulted in an overall destruction of AJ and detachment of cells from each other and from the extracellular matrix. AJ formation appears, therefore, to be modulated by a variety of factors including the level of expression of its intrinsic components, the cooperative effect of other adhesion molecules, and by tyrosinephosphorylation.