title: Pho5p and newly identified nucleotide pyrophosphatases/ phosphodiesterases regulate extracellular nucleotide phosphate metabolism in Saccharomyces cerevisiae.
abstract: Extracellular nucleotides play many biological roles, including intercellular communication and modulation of nucleotide receptor signaling, and are dependent on the phosphorylation state of the nucleotide. Regulation of nucleotide phosphorylation is necessary, and a specialized class of enzymes, nucleotide pyrophosphatases/phosphodiesterases (E-NPPs), has been identified in mammals to perform this function. Although the E-NPP class is conserved among complex eukaryotes, this system has not yet been identified in Saccharomyces cerevisiae. Using genetic and biochemical experiments, we show that two orthologs of the E-NPP family, referred to as Npp1p and Npp2p, exist in budding yeast and can perform nucleotide phosphate hydrolysis. This activity is enhanced during phosphate starvation, where hydrolyzed phosphates can be imported from extracellular sources and utilized to overcome phosphate starvation through the activity of the Pho5p acid phosphatase. The added compensatory effect by Pho5p is also a newly established role for Pho5p. This study demonstrates that extracellular nucleotide phosphate metabolism appears to be controlled by at least two independent regulatory mechanisms, uniting phosphate starvation with extracellular nucleotide regulation.
authors.affiliation: Department of Chemistry and Biochemistry, and UCSD Cancer Center, University of California, San Diego, La Jolla, CA 92093-0347, USA.
authors.forename: Eileen J
authors.initials: EJ
authors.lastname: Kennedy
authors.forename: Lorraine
authors.initials: L
authors.lastname: Pillus
authors.forename: Gourisankar
authors.initials: G
authors.lastname: Ghosh
mesh_terms: D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000235:genetics / Q000378:metabolism*; D000135:Acid Phosphatase; D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D006867:Hydrolases / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009711:Nucleotides / Q000737:chemistry / Q000378:metabolism*; D010710:Phosphates / Q000737:chemistry / Q000378:metabolism*; D011755:Pyrophosphatases / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment
chemical_list: D009711:Nucleotides; D010710:Phosphates; D029701:Saccharomyces cerevisiae Proteins; D006867:Hydrolases; C508485:Npp1 protein, S cerevisiae; C508486:Npp2 protein, S cerevisiae; D000135:Acid Phosphatase; C488916:PHO5 protein, S cerevisiae; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; D011755:Pyrophosphatases; C021899:nucleotide pyrophosphatase