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...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2001-07, Vol.61 (13), p.4985-4989
Main Authors: TOLKACHEVA, Tatyana, BODDAPATI, Manoranjan, SANFIZ, Anthony, TSUCHIDA, Kunihiro, KIMMELMAN, Alec C, CHAN, Andrew M-L
Format: Article
Language:English
Subjects:
3T3 Cells
Activin Receptors, Type II
Adaptor Proteins, Signal Transducing
Animals
Biological and medical sciences
Carrier Proteins - metabolism
Cell physiology
Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes
Fundamental and applied biological sciences. Psychology
Guanylate Kinases
Humans
Intercellular Junctions - enzymology
MAGI-2 protein
Mice
Molecular and cellular biology
Mutagenesis, Site-Directed
Nucleoside-Phosphate Kinase - metabolism
Phosphoric Monoester Hydrolases - genetics
Phosphoric Monoester Hydrolases - metabolism
Phosphorylation
Protein Binding
Protein Structure, Tertiary
Proteins
PTEN gene
PTEN Phosphohydrolase
threonine
Threonine - metabolism
Tumor Suppressor Proteins
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Summary: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.
ISSN:0008-5472
1538-7445