Ras and Gpa2 mediate one branch of a redundant glucose signaling pathway in yeast.
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.
Wang
Ying
Y
Department of Molecular Biology, Princeton University, Princeton, New Jersey, USA.
Pierce
Michael
M
Schneper
Lisa
L
Güldal
C Gökçe
CG
Zhang
Xiuying
X
Tavazoie
Saeed
S
Broach
James R
JR
D000483:Alleles; D001665:Binding Sites; D049109:Cell Proliferation; D016000:Cluster Analysis; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism; D044385:GTP-Binding Protein alpha Subunits / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000737:chemistry; D015966:Gene Expression Regulation, Fungal; D005947:Glucose / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000737:chemistry; D008928:Mitochondria / Q000378:metabolism; D015233:Models, Statistical; D009693:Nucleic Acid Hybridization; D012313:RNA / Q000737:chemistry; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D020218:Response Elements; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D018631:ras Proteins / Q000378:metabolism / Q000502:physiology*
D018076:DNA, Complementary; D005656:Fungal Proteins; C109334:GPR1 protein, S cerevisiae; D044385:GTP-Binding Protein alpha Subunits; D043562:Receptors, G-Protein-Coupled; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D012313:RNA; D006160:Guanosine Triphosphate; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D019204:GTP-Binding Proteins; C083907:Gpa2 protein, S cerevisiae; D018631:ras Proteins; D005947:Glucose