title: Metabolic gene products have evolved to interact with the cell wall integrity pathway in Saccharomyces cerevisiae.
abstract: Two of the five unlinked genes theoretically capable of encoding 5-phosphoribosyl-1(α)-pyrophosphate (PRPP) synthetase (Prs) in Saccharomyces cerevisiae, PRS1 and PRS5, contain in-frame insertions which separate the cation- and PRPP-binding sites, diagnostic of Prs polypeptides. The impairment of cell wall integrity (CWI) mitogen-activated protein kinase (MAPK) cascade in strains lacking PRS1 and the synthetic lethality associated with loss of PRS1 and PRS5 imply that these insertions are not gratuitous. Coimmunoprecipitation revealed that Prs1 interacts with the CWI MAPK pathway, only when Slt2 has been phosphorylated by Mkk1/2. Three serine residues identified by phosphoproteome analysis (Ficarro et al 2002) are located in one of the insertions of PRS5 thereby defining Prs5 as one of the 11 triply phosphorylated proteins in yeast. Mutation of these phosphosites compromised the transcriptional readout of one endpoint of the CWI pathway, Rlm1, as well as the expression of the gene encoding the stress-activated 1,3 β-glucan synthase, Fks2, regulated by a second endpoint of the CWI pathway, Swi4/Swi6 (SBF transcription factor). Therefore, the unexpected impairment of the CWI phenotype encountered in yeast strains either mutated or deleted for PRS1 or PRS5 can be explained by disruption of the communication between primary cell metabolism and CWI signalling.
authors.affiliation: School of Life Sciences, Heriot-Watt University, Edinburgh EH14 4AS, UK.
authors.forename: Eziuche A
authors.initials: EA
authors.lastname: Ugbogu
authors.affiliation: School of Life Sciences, Heriot-Watt University, Edinburgh EH14 4AS, UK.
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.affiliation: School of Life Sciences, Heriot-Watt University, Edinburgh EH14 4AS, UK.
authors.forename: Lilian M
authors.initials: LM
authors.lastname: Schweizer
authors.affiliation: School of Life Sciences, Heriot-Watt University, Edinburgh EH14 4AS, UK M.Schweizer@hw.ac.uk.|Institute of Biological Chemistry, Biophysics and Bioengineering, Heriot-Watt University, Edinburgh EH14 4AS, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Schweizer
mesh_terms: D002473:Cell Wall / Q000378:metabolism*; D019143:Evolution, Molecular; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D012268:Ribose-Phosphate Pyrophosphokinase / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D020928:Mitogen-Activated Protein Kinases; D012268:Ribose-Phosphate Pyrophosphokinase
keywords: cell signalling; cell wall integrity; mutagenesis in vitro, co-immunoprecipitation; nucleoside/nucleotide biosynthesis; protein phosphorylation; yeast physiology