Regulation of PTEN binding to MAGI-2 by two putative phosphorylation sites at 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 two threonine residues within this COOH-terminal region at codon 382 and 383 that may be targets for phosphorylation events. Interestingly, PTEN mutants rendered phosphorylation-incompetent 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.
Tolkacheva
T
T
The Derald H. Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York, New York 10029, USA.
Boddapati
M
M
Sanfiz
A
A
Tsuchida
K
K
Kimmelman
A C
AC
Chan
A M
AM
D016475:3T3 Cells; D030301:Activin Receptors, Type II; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D051528:Guanylate Kinases; D006801:Humans; D007365:Intercellular Junctions / Q000201:enzymology; D051379:Mice; D016297:Mutagenesis, Site-Directed; D009703:Nucleoside-Phosphate Kinase / Q000378:metabolism; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins; D013912:Threonine / Q000378:metabolism*; D025521:Tumor Suppressor Proteins
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D011506:Proteins; D025521:Tumor Suppressor Proteins; D013912:Threonine; D030301:Activin Receptors, Type II; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases; C485777:MAGI2 protein, human; C405684:Magi2 protein, mouse; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human