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Eukaryotic Cell, January 2005, p. 63-71, Vol. 4, No. 1
1535-9778/05/$08.00+0 doi:10.1128/EC.4.1.63-71.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
Tor and Cyclic AMP-Protein Kinase A: Two Parallel Pathways Regulating Expression of Genes Required for Cell Growth
Sara A. Zurita-Martinez and
Maria E. Cardenas*
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina
Received 22 October 2004/
Accepted 10 November 2004
In the budding yeast Saccharomyces cerevisiae, the Tor and cyclic AMP-protein kinase A (cAMP-PKA) signaling cascades respond to nutrients and regulate coordinately the expression of genes required for cell growth, including ribosomal protein (RP) and stress-responsive (STRE) genes. The inhibition of Tor signaling by rapamycin results in repression of the RP genes and induction of the STRE genes. Mutations that hyperactivate PKA signaling confer resistance to rapamycin and suppress the repression of RP genes imposed by rapamycin. By contrast, partial inactivation of PKA confers rapamycin hypersensitivity but only modestly affects RP gene expression. Complete inactivation of PKA impairs RP gene expression and concomitantly enhances STRE gene expression; remarkably, this altered transcriptional pattern is still sensitive to rapamycin and thus subject to Tor control. These findings illustrate how the Tor and cAMP-PKA signaling pathways respond to nutrient signals to govern gene expression required for cell growth via two parallel routes, and they have broad implication for our understanding of analogous regulatory networks in normal and neoplastic mammalian cells.
* Corresponding author. Mailing address: Department of Molecular Genetics and Microbiology, Duke University Medical Center, 322 CARL Bldg., Box 3546, Research Dr., Durham, NC 27710. Phone: (919) 684-2809. Fax: (919) 684-5458. E-mail: carde004{at}mc.duke.edu.
Eukaryotic Cell, January 2005, p. 63-71, Vol. 4, No. 1
1535-9778/05/$08.00+0 doi:10.1128/EC.4.1.63-71.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
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Copyright © 2005 by the American Society for Microbiology.