Interaction of Ga12 and Ga13 with the cytoplasmic domain of cadherin provides a mechanism for b-catenin release
نویسندگان
چکیده
The G12 subfamily of heterotrimeric G proteins, comprised of the a-subunits Ga12 and Ga13, 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 Ga12. 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. Ga12 or Ga13 binding causes dissociation of the transcriptional activator b-catenin from cadherins. Furthermore, in cells lacking the adenomatous polyposis coli protein required for b-catenin degradation, expression of mutationally activated Ga12 or Ga13 causes an increase in b-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.
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