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Activation of the RAS/cyclic AMP pathway suppresses a TOR deficiency in yeast

Tobias Schmelzle1, Thomas Beck, Dietmar E Martin

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

Molecular and Cellular Biology
|December 16, 2003
PubMed

Insights

The target of rapamycin (TOR) pathway signals through the RAS/cyclic AMP (cAMP) pathway in yeast. This interaction is independent of previously known TOR effectors, suggesting a novel TOR signaling branch.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Yeast Genetics

Background:

  • The target of rapamycin (TOR) and RAS/cyclic AMP (cAMP) signaling pathways are critical regulators of cell growth in response to nutrient availability in yeast.
  • Understanding the interplay between these two major pathways is essential for elucidating nutrient-sensing mechanisms.

Purpose of the Study:

  • To investigate the functional interaction between the TOR and RAS/cAMP signaling pathways in yeast.
  • To determine if the RAS/cAMP pathway mediates TOR signaling and identify the key components involved.

Main Methods:

  • Yeast genetics and molecular biology techniques were employed.
  • Rapamycin sensitivity assays were performed.
  • Analysis of gene expression, protein localization, and cellular processes like autophagy and ribosome biogenesis was conducted.

Main Results:

  • Activation of the RAS/cAMP pathway conferred resistance to rapamycin, a TOR inhibitor.
  • Constitutive RAS/cAMP activation blocked several rapamycin-induced responses, including MSN2 nuclear translocation, stress gene induction, glycogen accumulation, autophagy, ribosome biogenesis down-regulation, and HXT1 down-regulation.
  • These TOR-mediated effects were largely independent of known TOR effectors TAP42 and SIT4.
  • TOR signaling influenced the subcellular localization of protein kinase A (TPK1) and YAK1, key components of the RAS/cAMP pathway.

Conclusions:

  • The RAS/cAMP pathway acts as a novel effector branch for TOR signaling in yeast, independent of TAP42/SIT4.
  • TOR regulates the RAS/cAMP pathway by controlling the localization of TPK1 and YAK1.
  • This study reveals a previously uncharacterized link between nutrient sensing and cell growth control pathways.

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