Interaction of G alpha 12 and G alpha 13 with the cytoplasmic domain of cadherin provides a mechanism for beta-catenin release

The G11 subfamily of heterotrimeric G proteins, comprised of the alpha -sub units G alpha 12 and G alpha 13, has been implicated as a signaling compone nt in cellular processes ranging from cytoskeletal changes to cell growth a nd 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 cyto plasmic tails of several members of the cadherin family of cell-surface adh esion proteins. G alpha 12 or G alpha 13 binding causes dissociation of the transcriptional activator beta -catenin from cadherins, Furthermore, in ce lls lacking the adenomatous polyposis coil protein required for beta -caten in 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 li nk between heterotrimeric G proteins and cellular processes controlling gro wth and differentiation.