Livas et al. BMC Genomics 2011, 12:405 http://www.biomedcentral.com/1471-2164/12/405 R E S E A R C H A R T I C L E Open Access Transcriptional responses to glucose in Saccharomyces cerevisiae strains lacking a functional protein kinase A Daniela Livas1, Marinka JH Almering2, Jean-Marc Daran2, Jack T Pronk2 and Juana M Gancedo1* Abstract Background: The pattern of gene transcripts in the yeast Saccharomyces cerevisiae is strongly affected by the presence of glucose. An increased activity of protein kinase A (PKA), triggered by a rise in the intracellular concentration of cAMP, can account for many of the effects of glucose on transcription. In S. cerevisiae three genes, TPK1, TPK2, and TPK3, encode catalytic subunits of PKA. The lack of viability of tpk1 tpk2 tpk3 triple mutants may be suppressed by mutations such as yak1 or msn2/msn4. To investigate the requirement for PKA in glucose control of gene expression, we have compared the effects of glucose on global transcription in a wild-type strain and in two strains devoid of PKA activity, tpk1 tpk2 tpk3 yak1 and tpk1 tpk2 tpk3 msn2 msn4. Results: We have identified different classes of genes that can be induced -or repressed- by glucose in the absence of PKA. Representative examples are genes required for glucose utilization and genes involved in the metabolism of other carbon sources, respectively. Among the genes responding to glucose in strains devoid of PKA some are also controlled by a redundant signalling pathway involving PKA activation, while others are not affected when PKA is activated through an increase in cAMP concentration. On the other hand, among genes that do not respond to glucose in the absence of PKA, some give a full response to increased cAMP levels, even in the absence of glucose, while others appear to require the cooperation of different signalling pathways. We show also that, for a number of genes controlled by glucose through a PKA-dependent pathway, the changes in mRNA levels are transient. We found that, in cells grown in gluconeogenic conditions, expression of a small number of genes, mainly connected with the response to stress, is reduced in the strains lacking PKA. Conclusions: In S. cerevisiae, the transcriptional responses to glucose are triggered by a variety of pathways, alone or in combination, in which PKA is often involved. Redundant signalling pathways confer a greater robustness to the response to glucose, while cooperative pathways provide a greater flexibility. Background Adaptation to changing environmental conditions is of capital importance for the survival of organisms and their successful establishment in new ecological niches. To enable adaptation, sophisticated networks of signalling that govern growth and development have been selected in all living systems. In the model yeast Saccharomyces cerevisiae, availability of glucose or other easily fermenta- ble sugars elicits a drastic rearrangement of metabolism and multiple changes in its transcriptome. An immediate * Correspondence: jmgancedo@iib.uam.es 1Department of Metabolism and Cell Signalling, Instituto de Investigaciones Biomédicas Alberto Sols, CSIC-UAM, Arturo Duperier 4, 28029 Madrid, Spain Full list of author information is available at the end of the article consequence of the exposure to glucose is a rise in the concentration of internal cAMP [1,2], and it is well estab- lished that changes in cAMP levels affect the transcrip- tion rate of a large number of genes in S. cerevisiae [3-5]. The increase in cAMP levels is mainly due to the activa- tion of the plasma membrane-bound adenylate cyclase mediated by different G proteins, Ras1, Ras2 and Gpa2 [6,7]. The GDP-GTP exchange in the Ras1 or Ras2 pro- teins is mediated by Cdc25 [8], which is activated by glu- cose by an, as yet, unknown mechanism [9]. Activation of Gpa2, in turn, results from the binding of glucose to the transmembrane protein Gpr1 [10-12]. Bcy1, the regula- tory subunit of the cAMP-dependent protein kinase (PKA), when binding cAMP, dissociates from the © 2011 Livas et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.