Interaction of Gα12 and Gα13 with the cytoplasmic domain of cadherin provides a mechanism for β-catenin release

The G11 subfamily of heterotrimeric G proteins, comprised of the alpha -subunits G alpha 12 and G alpha 13, has been implicated as a signaling component in cellular processes ranging from cytoskeletal changes to cell growth and oncogenesis. In an attempt to elucidate specific roles of this subfamily in cell regulation, we sought to identify molecular targets of G alpha 12, Here we show a specific interaction between the G12 subfamily and the cytoplasmic tails of several members of the cadherin family of cell-surface adhesion proteins. G alpha 12 or G alpha 13 binding causes dissociation of the transcriptional activator beta -catenin from cadherins, Furthermore, in cells lacking the adenomatous polyposis coil protein required for beta -catenin degradation, expression of mutationally activated G alpha 12 or G alpha 13 causes an increase in beta -catenin-mediated transcriptional activation, These findings provide a potential molecular mechanism for the previously reported cellular transforming ability of the G12 subfamily and reveal a link between heterotrimeric G proteins and cellular processes controlling growth and differentiation.