Advances in Brief Regulation of PTEN Binding to MAGI-2 by Two Putative Phosphorylation Sites at Threonine 382 and 3831

We have reported previously that the PTEN COOH-terminal 33 amino acids play a role in the maintenance of PTEN protein stability (Tolkacheva and Chan, Oncogene, 19: 680–689, 2000). By site-directed mutagenesis, we identified two threonine residues within this COOHterminal region at codon 382 and 383 that may be targets for phosphorylation events. Interestingly, PTEN mutants rendered phosphorylationincompetent at these two sites, T382A/T383A, and were found to have drastically reduced expression in cultured cells. The enhanced degradation of PTEN was most likely mediated by the proteosome-dependent pathway, we have evidence that PTEN was polyubiquitinated. More interestingly, the non-phosphorylated forms of PTEN displayed significantly greater binding affinity than the wild-type protein to a previously identified PTEN interacting partner, MAGI-2/ARIP1. On the basis of all these data, we propose that PTEN recruitment to the cell-cell junction may be regulated through the phosphorylation of its COOH terminus.