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Eukaryotic Cell, November 2005, p. 1892-1901, Vol. 4, No. 11
1535-9778/05/$08.00+0     doi:10.1128/EC.4.11.1892-1901.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Pho5p and Newly Identified Nucleotide Pyrophosphatases/ Phosphodiesterases Regulate Extracellular Nucleotide Phosphate Metabolism in Saccharomyces cerevisiae

Eileen J. Kennedy,1 Lorraine Pillus,2* and Gourisankar Ghosh1*

Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093-0375,1 Division of Biological Sciences, Section of Molecular Biology, and UCSD Cancer Center, University of California, San Diego, La Jolla, California 92093-03472

Received 18 August 2005/ Accepted 24 August 2005

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.

* Corresponding author. Mailing address for Lorraine Pillus: Division of Biological Sciences, Section of Molecular Biology, and UCSD Cancer Center, University of California, San Diego, La Jolla, CA 92093-0347. Phone: (858) 822-2442. Fax: (858) 534-7053. E-mail: lpillus{at}biomail.ucsd.edu. Mailing address for Gourisankar Ghosh: Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093-0375. Phone: (858) 822-0469. Fax: (858) 822-1408. E-mail: gghosh{at}chem.ucsd.edu.

Eukaryotic Cell, November 2005, p. 1892-1901, Vol. 4, No. 11
1535-9778/05/$08.00+0     doi:10.1128/EC.4.11.1892-1901.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.





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