Cadherins are cell adhesion molecules concentrated at intercellular ad
herens junctions, where they form a multiprotein complex with cytoplas
mic catenins. Although cell-cell interactions affect many aspects of c
ell behavior, little is known about signaling pathways triggered by ca
dherin engagement. We show here that E-cadherin-mediated cell-cell adh
esion leads to a rapid increase in tyrosine phosphorylation at sites o
f cell-cell contact and that this stimulation of tyrosine phosphorylat
ion can be mimicked by aggregation of E-cadherin with antibodies. The
proteins that become phosphorylated are distinct from those previously
shown to be tyrosine phosphorylated in response to integrin-mediated
adhesion and include ras-GAP. We also find that E-cadherin-mediated ty
rosine phosphorylation is not required for the assembly of adherens-ty
pe junctions.