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Rictor phosphorylation on the Thr-1135 site does not require mammalian target of rapamycin complex 2

Delphine Boulbes1, Chien-Hung Chen, Tattym Shaikenov

  • 1Department of Molecular and Cellular Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.

Molecular Cancer Research : MCR
|May 27, 2010
PubMed

Insights

Growth factors regulate cell survival via the phosphoinositide 3-kinase/Akt pathway. Rictor phosphorylation on Thr-1135 is linked to mTORC2 activation but not critical for Akt regulation, suggesting other roles.

Area of Science:

  • Cell biology
  • Molecular oncology
  • Signal transduction

Background:

  • Growth factors control cell proliferation and survival through the phosphoinositide 3-kinase/Akt pathway.
  • Dysregulation of this pathway is implicated in numerous human cancers.
  • Mammalian target of rapamycin complex 2 (mTORC2) is a key regulator of Akt Ser-473 phosphorylation.

Purpose of the Study:

  • To investigate the role of rictor phosphorylation at Thr-1135 in mTORC2 activation and function.
  • To determine if rictor Thr-1135 phosphorylation is essential for growth factor-induced Akt phosphorylation.
  • To explore potential mTORC2-independent functions of rictor modification.

Main Methods:

  • Utilized rictor null mouse embryonic fibroblasts.
  • Employed phospho-mutant rictor substitutions.
  • Analyzed growth factor stimulation, oncogenic ras/PI3K expression, and inhibition of PI3K, mTOR, and integrin-linked kinase.

Main Results:

  • Rictor phosphorylation on Thr-1135 is induced by growth factors, oncogenic ras, or PI3K.
  • This phosphorylation is sensitive to PI3K, mTOR, or integrin-linked kinase inhibition.
  • Rictor Thr-1135 phospho-mutants did not affect growth factor-dependent Akt phosphorylation, indicating it's not critical for mTORC2 kinase activity.
  • Rictor phosphorylation occurs even in mTORC2-deficient cells.

Conclusions:

  • Rictor Thr-1135 phosphorylation is associated with mTORC2 activation but not essential for its kinase activity towards Akt.
  • This modification may regulate both mTORC2-dependent and mTORC2-independent functions of rictor.
  • Further research is warranted to elucidate the precise role of rictor Thr-1135 phosphorylation in cellular signaling.

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