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PMID: 15138498 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Ras and Gpa2 mediate one branch of a redundant glucose signaling pathway in yeast.

PLoS biology ·Vol. 2 ·No. 5 ·2004-05-00 ·Pages E128

Wang Y, Pierce M, Schneper L, Güldal CG, Zhang X, Tavazoie S, Broach JR

Abstract

Addition of glucose to starved yeast cells elicits a dramatic restructuring of the transcriptional and metabolic state of the cell. While many components of the signaling network responsible for this response have been identified, a comprehensive view of this network is lacking. We have used global analysis of gene expression to assess the roles of the small GTP-binding proteins, Ras2 and Gpa2, in mediating the transcriptional response to glucose. We find that 90% of the transcriptional changes in the cell attendant on glucose addition are recapitulated by activation of Ras2 or Gpa2. In addition, we find that protein kinase A (PKA) mediates all of the Ras2 and Gpa2 transcriptional effects. However, we also find that most of the transcriptional effects of glucose addition to wild-type cells are retained in strains containing a PKA unresponsive to changes in cAMP levels. Thus, most glucose-responsive genes are regulated redundantly by a Ras/PKA-dependent pathway and by one or more PKA-independent pathways. Computational analysis extracted RRPE/PAC as the major response element for Ras and glucose regulation and revealed additional response elements mediating glucose and Ras regulation. These studies provide a paradigm for extracting the topology of signal transduction pathways from expression data.

MeSH Terms
Alleles Binding Sites Cell Proliferation Cluster Analysis Cyclic AMP/metabolism Cyclic AMP-Dependent Protein Kinases/metabolism DNA, Complementary/metabolism Fungal Proteins/metabolism GTP-Binding Protein alpha Subunits/metabolism GTP-Binding Proteins/chemistry Gene Expression Regulation, Fungal Glucose/metabolism Guanosine Triphosphate/chemistry Mitochondria/metabolism Models, Statistical Nucleic Acid Hybridization RNA/chemistry Receptors, G-Protein-Coupled/metabolism Response Elements Saccharomyces cerevisiae/metabolism Saccharomyces cerevisiae Proteins/metabolism Signal Transduction Transcription Factors/metabolism Transcription, Genetic ras Proteins/metabolism,physiology
Chemicals
DNA, Complementary Fungal Proteins GPR1 protein, S cerevisiae GTP-Binding Protein alpha Subunits Receptors, G-Protein-Coupled Saccharomyces cerevisiae Proteins Transcription Factors RNA Guanosine Triphosphate Cyclic AMP Cyclic AMP-Dependent Protein Kinases GTP-Binding Proteins Gpa2 protein, S cerevisiae ras Proteins Glucose
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Wang Ying
Department of Molecular Biology, Princeton University, Princeton, New Jersey, USA.
Pierce Michael
Schneper Lisa
Güldal C Gökçe
Zhang Xiuying
Tavazoie Saeed
Broach James R
Conflict of Interest

The authors have declared that no conflicts of interest exist.

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Article Info
Journal
PLoS biology
Abbr.
PLoS Biol
ISSN
1545-7885
DOI
10.1371/journal.pbio.0020128
Published
2004-05-00
Epub
2004-00-11
Pages
E128
Language
English
Region
United States
NLM ID
101183755
PMCID
PMC406390
Subset
IM
Grants
NCI NIH HHS · P01 CA041086 · United States
NCI NIH HHS · CA41086 · United States
External Links
PubMed source DOI: 10.1371/journal.pbio.0020128 PMC Full Text View journal details
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