Regulation of PTEN binding to MAGI-2 by two putative phosphorylation sitesat threonine 382 and 383

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 t wo threonine residues within this COOH-terminal region at codon 382 and 383 that may be targets for phosphorylation events. Interestingly, PTEN mutant s rendered phosphorylation-incompetent at these two sites, T382A/T383A, and were found to have drastically reduced expression in cultured cells. The e nhanced degradation of PTEN was most likely mediated by the proteosome-depe ndent pathway, we have evidence that PTEN was polyubiquitinated. More inter estingly, the non-phosphorylated forms of PTEN displayed significantly grea ter 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 th rough the phosphorylation of its COOH terminus.