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Development and Application of Rapamycin-regulated Tyrosine Phosphatases
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The rapamycin-sensitive phosphoproteome reveals that TOR controls protein kinase A toward some but not all substrates

Alexandre Soulard1, Alessio Cremonesi, Suzette Moes

  • 1Biozentrum, University of Basel, CH-4056 Basel, Switzerland.

Molecular Biology of the Cell
|August 13, 2010
PubMed

Insights

The Target of Rapamycin (TOR) complex 1 (TORC1) pathway activates protein kinase A (PKA) by inhibiting BCY1 phosphorylation. This regulation allows TORC1 to control cell growth processes effectively.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Cell growth regulation involves intricate coordination of transcription, ribosome biogenesis, translation, metabolism, and autophagy.
  • In yeast, protein kinases Target of Rapamycin (TOR) and protein kinase A (PKA) are key nutrient-responsive activators of cell growth.
  • The precise coordination between TOR and PKA signaling pathways remains unclear.

Purpose of the Study:

  • To elucidate the coordination mechanisms between TOR and PKA signaling pathways in regulating cellular processes.
  • To investigate how TOR complex 1 (TORC1) influences PKA activity and substrate specificity.
  • To understand the role of BCY1 phosphorylation in PKA regulation by TORC1.

Main Methods:

  • Quantitative analysis of the rapamycin-sensitive phosphoproteome.
  • Targeted analysis of PKA substrates.
  • Phosphorylation site analysis (e.g., T129 on BCY1).

Main Results:

  • TORC1 activates PKA toward a specific subset of substrates.
  • TORC1 signaling impacts BCY1, the PKA negative regulator.
  • Rapamycin treatment of TORC1 leads to BCY1 phosphorylation at T129, activating BCY1 and inhibiting PKA.
  • TORC1 signaling inhibits BCY1 T129 phosphorylation via SCH9 and MPK1, thereby preventing PKA inhibition.

Conclusions:

  • TORC1 activates PKA for specific substrates by preventing MPK1-mediated BCY1 activation.
  • This provides a mechanism for how TORC1 coordinates cell growth through differential PKA regulation.

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