Linked Life Data

15006350

Source:http://linkedlifedata.com/resource/pubmed/id/15006350

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2004-3-9
pubmed:abstractText
Multisite hyperphosphorylation of tau has been implicated in the pathogenesis of neurodegenerative diseases including Alzheimer's disease (AD). However, the phosphorylation events critical for tau toxicity and mechanisms regulating these events are largely unknown. Here we show that Drosophila PAR-1 kinase initiates tau toxicity by triggering a temporally ordered phosphorylation process. PAR-1 directly phosphorylates tau at S262 and S356. This phosphorylation event is a prerequisite for the action of downstream kinases, including glycogen synthase kinase 3 (GSK-3) and cyclin-dependent kinase-5 (Cdk5), to phosphorylate several other sites and generate disease-associated phospho-epitopes. The initiator role of PAR-1 is further underscored by the fact that mutating PAR-1 phosphorylation sites causes a much greater reduction of overall tau phosphorylation and toxicity than mutating S202, one of the downstream sites whose phosphorylation depends on prior PAR-1 action. These findings begin to differentiate the effects of various phosphorylation events on tau toxicity and provide potential therapeutic targets.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0092-8674
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
116
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
671-82
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15006350-Animals, pubmed-meshheading:15006350-Animals, Genetically Modified, pubmed-meshheading:15006350-Cyclin-Dependent Kinase 5, pubmed-meshheading:15006350-Cyclin-Dependent Kinases, pubmed-meshheading:15006350-Drosophila Proteins, pubmed-meshheading:15006350-Drosophila melanogaster, pubmed-meshheading:15006350-Glycogen Synthase Kinase 3, pubmed-meshheading:15006350-Mutagenesis, Site-Directed, pubmed-meshheading:15006350-Neurodegenerative Diseases, pubmed-meshheading:15006350-Phenotype, pubmed-meshheading:15006350-Phosphorylation, pubmed-meshheading:15006350-Photoreceptor Cells, Invertebrate, pubmed-meshheading:15006350-Protein Kinases, pubmed-meshheading:15006350-Protein-Serine-Threonine Kinases, pubmed-meshheading:15006350-Signal Transduction, pubmed-meshheading:15006350-tau Proteins
pubmed:year
2004
pubmed:articleTitle
PAR-1 kinase plays an initiator role in a temporally ordered phosphorylation process that confers tau toxicity in Drosophila.
pubmed:affiliation
Laboratory of Developmental Neurobiology, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't