Levels of PTEN protein modulate Akt phosphorylation on serine 473, but not on threonine 308, in IGF-II-overexpressing rhabdomyosarcomas cells

Xiaolin Wan, Lee J. Helman

Research output: Contribution to journalArticle

Abstract

Constitutive activation of Akt has been found in many types of human cancer, and is believed to promote proliferation and increased cell survival thereby contributing to cancer progression. In this study, we examined Akt phosphorylation on Ser473 and Thr308 in seven IGF-II-overexpressing rhabdomyosarcomas (RMS) cells. All the RMS cell lines tested had high levels of Akt phosphorylation on Thr308, whereas three cell lines (Rh5, Rh18, and CTR) had a much lower level of Akt phosphorylation on Ser473. To determine whether the difference in Akt phosphorylation on Ser473, but not on Thr308, observed among cell lines is a cell-specific phenomenon or due to other factors, which possibly downregulate Akt phosphorylation, we examined expression of PTEN protein, which acts as a negative regulator of the PI3K/Akt signaling pathway through its ability to dephosphorylate phosphatidylinositol 3,4,5-triphosphate (PIP3). The levels of PTEN expression inversely correlate with Akt phosphorylation on Ser473, but not on Thr308. Consistent with this finding, transfection of wild-type PTEN into RMS and mouse myoblast C2C12 cells resulted in reduced Akt phosphorylation on Ser473, but not on Thr308. Our data suggest that Ser473 may be a key target residue for PTEN to modulate the effects of IGF-II on activating the PI3K/Akt pathway in RMS cells. A better understanding of the pathway in RMS will likely contribute to insights into the biology of the RMS tumorigenesis and hopefully lead to novel therapeutic options.

Original languageEnglish (US)
Pages (from-to)8205-8211
Number of pages7
JournalOncogene
Volume22
Issue number50
DOIs
StatePublished - Nov 6 2003

Keywords

  • Akt
  • PTEN
  • Phosphorylation

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Fingerprint Dive into the research topics of 'Levels of PTEN protein modulate Akt phosphorylation on serine 473, but not on threonine 308, in IGF-II-overexpressing rhabdomyosarcomas cells'. Together they form a unique fingerprint.

  • Cite this