Interaction of the adaptor protein she and the adhesion molecule cadherin

In mitogenic signaling pathways, She participates in the growth factor activation of Ras by interacting with activated receptors and/or the Grb-2-Sos complex. Using several experimental approaches we demonstrate that Shc, through its SH2 domain, forms a complex with the cytoplasmic domain of cadherin, a transmembrane protein involved in the Ca2+-dependent regulation of cell-cell adhesion. This interaction is demonstrated in a yeast two-hybrid assay, by co-precipitation from mammalian cells, and by direct biochemical analysis in vitro. The Shc-cadherin association is phosphotyrosine-dependent and is abrogated by addition of epidermal growth factor to A-431 cells maintained in Ca2+-free medium, a condition that promotes changes in cell shape. She may therefore participate in the control of cell cell adhesion as well as mitogenic signaling through Ras.