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

PLoS Biol. 2004 May;2(5):E128. doi: 10.1371/journal.pbio.0020128. Epub 2004 May 11.

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.

Publication types

  • 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.

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
  • ras Proteins / physiology*

Substances

  • 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