AUGMENTATION OF ADHERENS JUNCTION FORMATION IN MESENCHYMAL CELLS BY COEXPRESSION OF N-CAM OR SHORT-TERM STIMULATION OF TYROSINE PHOSPHORYLATION

Adherens-type junctions (AJ) are specialized intercellular contacts, m ediated by cadherins and characterized by the association with actin f ilaments through a vinculin- and catenin-rich submembrane plaque. We d escribe here two mechanisms which potentiate AJ formation in mesenchym al cells. These include the augmentation of AT by the co-expression of another adhesion molecule, namely NCAM, and the stimulation of tyrosi ne phosphorylation. These effects were obtained in NIH-3T3 cells, whic h, under normal conditions, have poor cadherin- and vinculin-containin g intercellular junctions. The transfection of these cells with cDNA e ncoding 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 CO S cells, upon a brief exposure to H2O2/vanadate, which elevates cellul ar levels of phosphotyrosine due to inhibition of tyrosine-specific ph osphatases. This induction was, however, transient since prolonged exp osure to H2O2/vanadate resulted in an overall destruction of AJ and de tachment of cells from each other and from the extracellular matrix. A J formation appears, therefore, to be modulated by a variety of factor s including the level of expression of its intrinsic components, the c ooperative effect of other adhesion molecules, and by tyrosine-phospho rylation.