Linked Life Data

19754463

Source:http://linkedlifedata.com/resource/pubmed/id/19754463

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 5
pubmed:dateCreated
2009-9-16
pubmed:abstractText
Prs [PRPP (phosphoribosyl pyrophosphate) synthetase] catalyses the transfer of pyrophosphate from ATP to ribose 5-phosphate, thereby activating the pentose sugar for incorporation into purine and pyrimidine nucleotides. The Saccharomyces cerevisiae genome contains five genes, PRS1-PRS5, whose products display characteristic PRPP and bivalent-cation-binding sites of Prs polypeptides. Deletion of one or more of the five PRS genes has far-reaching and unexpected consequences, e.g. impaired cell integrity, temperature-sensitivity and sensitivity to VPA (valproic acid) and LiCl. CTP pools in prs1Delta and prs3Delta are reduced to 12 and 31% of the wild-type respectively, resulting in an imbalance in phospholipid metabolism which may have an impact on the intracellular inositol pool which is affected by the administration of either VPA or LiCl. Overexpression of CTP synthetase in prs1Delta prs3Delta strains partially reverses the VPA-sensitive phenotype. Yeast two-hybrid screening revealed that Prs3 and the yeast orthologue of GSK3 (glycogen synthase kinase 3), Rim11, a serine/threonine kinase involved in several signalling pathways, interact with each other. Furthermore, Prs5, an essential partner of Prs3, which also interacts with GSK3 contains three neighbouring phosphorylation sites, typical of GSK3 activation. These studies on yeast PRPP synthetases bring together and expand the current theories for the mood-stabilizing effects of VPA and LiCl in bipolar disorder.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1470-8752
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1115-20
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Valproic acid- and lithium-sensitivity in prs mutants of Saccharomyces cerevisiae.
pubmed:affiliation
Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't