The c-jun-N-terminal protein kinases (JNK) belong to the mitogen activated protein kinase (MAPK) group of serine/threonine protein kinases. They are primarily activated in response to stress and induce a diverse set of responses ranging from apoptosis to cell survival. Here we show that inhibition of JNK activity by the chemical inhibitor SP600125 induces cell-cell adhesion in human epidermal keratinocytes, human squamous carcinoma cells, A431 and MDCK cells under low Ca2+ conditions and in serum free medium. Furthermore, inhibition of JNK led to translocation of adherens junction proteins E-Cadherin and β-catenin to the cell surface in 30 minutes. Immuno-precipitation studies showed that after SP600125 treatment binding of E-cadherin to β-catenin increased, suggesting that translocation to the cell surface was accompanied by formation of adherens junctions. Interestingly, all these effects were reversed upon removal of the JNK inhibitor. In addition, dominant negative mutants and siRNA inhibition of the JNK pathway are currently under way to verify the role of this signaling pathway in cell-cell communication. Finally, we are currently investigating how these molecular events and JNK-mediated cell-cell adhesions may affect keratinocyte migration and wound healing.