T606-phosphorylated Kaiso interacting with 14-3-3 and p120ctn is sequestered in the cytoplasm of human cells

Kaiso is a transcription factor in the nucleus and p120ctn-binding protein in the cytoplasm. Although it is known that p120ctn is involved in Kaiso cytoplasmic-nuclear transportation, regulatory mechanisms of Kaiso transportation remain to be explored. We firstly found that Kaiso could directly interact with 14-3-3 family proteins, depending on the phosphorylation at the 606 threonine residue (T606) within the RSSTIP motif of Kaiso. AKT1 could phosphorylate Kaiso at T606. T606A mutation abolished most Kaiso–14-3-3 interaction. Notably, we found that the phosphorylated Kaiso (pT606-Kaiso) could also bind to p120ctn in the cytoplasm and block the cytoplasmic–nuclear transportation of Kaiso. The present study indicates, for the first time, that Kaiso can be phosphorylated by AKT1 at T606 and that pT606-Kaiso can bind both 14-3-3 and p120ctn proteins in the cytoplasm. The pT606-Kaiso–p120ctn (and 14-3-3) complexes cannot shift to the nucleus and accumulate in the cytoplasm. T606 phosphorylation regulates intracellular transportation of Kaiso.