These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Gi-coupled P2Y-ADP receptor mediates GSK-3 phosphorylation and beta-catenin nuclear translocation in granule neurons.
    Author: Ortega F, Pérez-Sen R, Miras-Portugal MT.
    Journal: J Neurochem; 2008 Jan; 104(1):62-73. PubMed ID: 17986231.
    Abstract:
    Glycogen synthase kinase-3 (GSK-3) is a multifaceted enzyme involved in development, neurogenesis, and survival at the CNS. We investigated nucleotides signaling to GSK-3 in cerebellar granule neurons and found that the metabotropic agonist 2-methyl-thio-ADP (2MeSADP) was able to induce GSK-3 phosphorylation and inhibition of its catalytic activity. 2MeSADP could be acting through several P2Y-ADP receptors expressed in granule neurons, as RT-PCR expression was found for P2Y(1), P2Y(12), and P2Y(13) receptors, but the pharmacological data fitted well with a Gi-coupled P2Y(13) receptor: the effect was sensitive to pertussis toxin, was unaffected by specific antagonists of P2Y(1) and P2Y(12) receptors, such as 2'-deoxy-N(6)-methyl-adenosine 3',5'-diphosphate and 2-methyl-thio-AMP, respectively, and the EC(50) values for 2MeSADP and ADP were in the same low nanomolar range. 2MeSADP was able to phosphorylate and activate extracellular signal-regulated kinase (ERK)-1,2 and Akt proteins, but its effect on GSK-3 phosphorylation was primarily dependent on the phosphatidyl inositol-3 kinase (PI3-K)/Akt pathway, as it was abolished by the PI3-K inhibitor wortmannin. GSK-3 inactivation by 2MeSADP in granule neurons resulted in nuclear translocation of its substrate beta-catenin, which functions as a transcriptional regulator, this effect being lost with wortmaninn. The present study first describes the coupling of a Gi-coupled P2Y(13)-like receptor to GSK-3 and beta-catenin through PI3-K/Akt signaling.
    [Abstract] [Full Text] [Related] [New Search]