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

Tatyana Tolkacheva, Manoranjan Boddapati, Anthony Sanfiz, Alec C. Kimmelman, Andrew M.L. Chan, Kunihiro Tsuchida

Research output: Contribution to journalArticle

113 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)4985-4989
Number of pages5
JournalCancer Research
Volume61
Issue number13
Publication statusPublished - 01-07-2001
Externally publishedYes

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Threonine
Phosphorylation
PTEN Phosphohydrolase
Intercellular Junctions
Protein Stability
Site-Directed Mutagenesis
Oncogenes
Codon
Cultured Cells
Maintenance
Amino Acids
Proteins

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Tolkacheva, T., Boddapati, M., Sanfiz, A., Kimmelman, A. C., Chan, A. M. L., & Tsuchida, K. (2001). Regulation of PTEN binding to MAGI-2 by two putative phosphorylation sites at threonine 382 and 383. Cancer Research, 61(13), 4985-4989.
Tolkacheva, Tatyana ; Boddapati, Manoranjan ; Sanfiz, Anthony ; Kimmelman, Alec C. ; Chan, Andrew M.L. ; Tsuchida, Kunihiro. / Regulation of PTEN binding to MAGI-2 by two putative phosphorylation sites at threonine 382 and 383. In: Cancer Research. 2001 ; Vol. 61, No. 13. pp. 4985-4989.
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Tolkacheva, T, Boddapati, M, Sanfiz, A, Kimmelman, AC, Chan, AML & Tsuchida, K 2001, 'Regulation of PTEN binding to MAGI-2 by two putative phosphorylation sites at threonine 382 and 383', Cancer Research, vol. 61, no. 13, pp. 4985-4989.

Regulation of PTEN binding to MAGI-2 by two putative phosphorylation sites at threonine 382 and 383. / Tolkacheva, Tatyana; Boddapati, Manoranjan; Sanfiz, Anthony; Kimmelman, Alec C.; Chan, Andrew M.L.; Tsuchida, Kunihiro.

In: Cancer Research, Vol. 61, No. 13, 01.07.2001, p. 4985-4989.

Research output: Contribution to journalArticle

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Tolkacheva T, Boddapati M, Sanfiz A, Kimmelman AC, Chan AML, Tsuchida K. Regulation of PTEN binding to MAGI-2 by two putative phosphorylation sites at threonine 382 and 383. Cancer Research. 2001 Jul 1;61(13):4985-4989.