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

• Main Authors: Ying Wang, Michael Pierce, Lisa Schneper, C Gökçe Güldal, Xiuying Zhang, Saeed Tavazoie, James R Broach
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2004-05-01
• Series: PLoS Biology
• Online Access: http://europepmc.org/articles/PMC406390?pdf=render

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.