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PLD1 regulates mTOR signaling and mediates Cdc42 activation of S6K1

Yimin Fang1, In-Hyun Park, Ai-Luen Wu

  • 1Department of Cell and Structural Biology, University of Illinois at Urbana-Champaign, 601 S. Goodwin Avenue B107, Urbana, IL 61801, USA.

Current Biology : CB
|December 5, 2003
PubMed
Abstract

Insights

Phospholipase D 1 (PLD1) regulates mammalian target of rapamycin (mTOR) signaling and cell growth. This study shows PLD1 mediates S6K1 activation by Cdc42, connecting mitogenic signals to mTOR.

Area of Science:

  • Cellular Biology
  • Molecular Signaling
  • Biochemistry

Background:

  • Mammalian target of rapamycin (mTOR) controls cell growth and proliferation.
  • mTOR signaling involves downstream targets ribosomal S6 kinase 1 (S6K1) and eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1).
  • Phosphatidic acid (PA) mediates mitogenic activation of mTOR signaling.

Purpose of the Study:

  • To investigate if phospholipase D 1 (PLD1) is an upstream regulator of mTOR.
  • To determine if Cdc42 activation of S6K1 is mediated by PLD1.

Main Methods:

  • Overexpression and knockdown of PLD1 using RNA interference (RNAi).
  • Utilized a rapamycin-resistant S6K1 mutant.
  • Investigated the role of Cdc42 mutations in PLD1 activation and S6K1 activity.

Main Results:

  • Overexpression of wild-type PLD1 increased S6K1 activity; inactive PLD1 had a dominant-negative effect.
  • PLD1 knockdown inhibited serum-stimulated S6K1 activation and 4E-BP1 hyperphosphorylation, reducing cell size.
  • Cdc42 activates S6K1 via the mTOR pathway, with PLD1 mediating this process.

Conclusions:

  • PLD1 is involved in mTOR signaling and cell size control.
  • A molecular mechanism for Cdc42 activation of S6K1 through PLD1 and PA is proposed.
  • This pathway connects mitogenic signals to mTOR.

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