Raptor-rictor axis in TGFβ-induced protein synthesis

Falguni Das, Nandini Ghosh-Choudhury, Lenin Mahimainathan, Balachandar Venkatesan, Denis Feliers, Daniel J. Riley, Balakuntalam S. Kasinath, Goutam Ghosh Choudhury

Research output: Contribution to journalArticlepeer-review

56 Scopus citations


Transforming growth factor-β (TGFβ) stimulates pathological renal cell hypertrophy for which increased protein synthesis is critical. The mechanism of TGFβ-induced protein synthesis is not known, but PI 3 kinase-dependent Akt kinase activity is necessary. We investigated the contribution of downstream effectors of Akt in TGFβ-stimulated protein synthesis. TGFβ increased inactivating phosphorylation of Akt substrate tuberin in a PI 3 kinase/Akt dependent manner, resulting in activation of mTOR kinase. mTOR activity increased phosphorylation of S6 kinase and the translation repressor 4EBP-1, which were sensitive to inhibition of both PI 3 kinase and Akt. mTOR inhibitor rapamycin and a dominant negative mutant of mTOR suppressed TGFβ-induced phosphorylation of S6 kinase and 4EBP-1. PI 3 kinase/Akt and mTOR regulated dissociation of 4EBP-1 from eIF4E to make the latter available for binding to eIF4G. mTOR and 4EBP-1 modulated TGFβ-induced protein synthesis. mTOR is present in two multi protein complexes, mTORC1 and mTORC2. Raptor and rictor are part of mTORC1 and mTORC2, respectively. shRNA-mediated downregulation of raptor inhibited TGFβ-stimulated mTOR kinase activity, resulting in inhibition of phosphorylation of S6 kinase and 4EBP-1. Raptor shRNA also prevented protein synthesis in response to TGFβ. Downregulation of rictor inhibited serine 473 phosphorylation of Akt without any effect on phosphorylation of its substrate, tuberin. Furthermore, rictor shRNA increased phosphorylation of S6 kinase and 4EBP-1 in TGFβ-independent manner, resulting in increased protein synthesis. Thus mTORC1 function is essential for TGFβ-induced protein synthesis. Our data also provide novel evidence that rictor negatively regulates TORC1 activity to control basal protein synthesis, thus conferring tight control on cellular hypertrophy.

Original languageEnglish (US)
Pages (from-to)409-423
Number of pages15
JournalCellular Signalling
Issue number2
StatePublished - Feb 2008


  • 4EBP-1
  • Akt
  • S6 kinase
  • Tuberin
  • eIF4E
  • mTORC1
  • mTORC2

ASJC Scopus subject areas

  • Cell Biology


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