Linked Life Data

16810687

Source:http://linkedlifedata.com/resource/pubmed/id/16810687

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2006-8-24
pubmed:abstractText
Glycogen synthase kinase (GSK)-3 was identified initially as an enzyme that regulates glycogen synthesis in response to insulin, but more recent studies indicate that it is also involved in numerous cellular processes, including cell survival, cell cycle regulation, proliferation, and differentiation. Because extracellular ATP exerts trophic actions on astrocytes, we investigated a possible signaling linkage from P2 purinergic receptors to GSK3beta. Addition of ATP to primary cultures of rat cortical astrocytes resulted in phosphorylation of Ser9 on GSK3beta and a concomitant decrease in GSK3 activity. UTP and 2',3'-O-(4-benzoyl)-benzoyl ATP (BzATP) increased phosphorylation of Ser9 on GSK3beta indicating that metabotropic P2Y and ionotropic P2X receptors are coupled to GSK3beta. Signaling studies showed that phosphorylation of Ser9-GSK3beta in response to ATP was inhibited by downregulation of protein kinase C (PKC) but not by blockade of Akt or p70 S6 kinase pathways. PKC also links P2 receptors to ERK in astrocytes, but inhibition of ERK signaling did not block phosphorylation of Ser9-GSK3beta stimulated by P2 receptors. Mechanical strain, which releases ATP, also stimulated Ser9 phosphorylation and this was attenuated by hydrolysis of extracellular ATP with apyrase or by blockade of P2 receptors. We conclude that P2 receptors are coupled to GSK3beta by a PKC-dependent pathway that is independent of Akt, p70 S6 kinase, and ERK pathways. These findings suggest that purinergic signaling contributes to the regulation of GSK3beta functions, one of which may be the response of astrocytes to CNS injury on release of ATP.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0360-4012
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
84
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
515-24
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed-meshheading:16810687-Adenosine Triphosphate, pubmed-meshheading:16810687-Animals, pubmed-meshheading:16810687-Astrocytes, pubmed-meshheading:16810687-Cells, Cultured, pubmed-meshheading:16810687-Extracellular Signal-Regulated MAP Kinases, pubmed-meshheading:16810687-Glycogen Synthase Kinase 3, pubmed-meshheading:16810687-Phosphorylation, pubmed-meshheading:16810687-Protein Kinase C, pubmed-meshheading:16810687-Proto-Oncogene Proteins c-akt, pubmed-meshheading:16810687-Rats, pubmed-meshheading:16810687-Rats, Inbred F344, pubmed-meshheading:16810687-Receptors, Purinergic P2, pubmed-meshheading:16810687-Receptors, Purinergic P2X, pubmed-meshheading:16810687-Serine, pubmed-meshheading:16810687-Signal Transduction, pubmed-meshheading:16810687-Stress, Mechanical, pubmed-meshheading:16810687-Uridine Triphosphate
pubmed:year
2006
pubmed:articleTitle
P2 purinergic receptors signal to glycogen synthase kinase-3beta in astrocytes.
pubmed:affiliation
Research Service, Miami VA Healthcare System, Miami, Florida.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural