Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2010-3-11
pubmed:abstractText
In previous works, we found that PTH promotes the apoptosis of human Caco-2 intestinal cells, through the mitochondrial pathway. This study was conducted to investigate the modulation of different players implicated in the AKT survival pathway in PTH-induced intestinal cell apoptosis. We demonstrate, for the first time, that PTH modulates AKT phosphorylation in response to apoptosis via the serine/threonine phosphatase PP2A. PTH treatment induces an association of AKT with the catalytic subunit of PP2A and increases its phosphatase activity. PTH also promotes the translocation of PP2Ac from the cytosol to the mitochondria. Furthermore, our results suggest that PP2A plays a role in hormone-dependent Caco-2 cells viability and in the cleavage of caspase-3 and its substrate PARP. The cAMP pathway also contributes to PTH-mediated AKT dephosphorylation while PKC and p38 MAPK do not participate in this event. Finally, we show that PTH induces the dissociation between 14-3-3 and AKT, but the significance of this response remains unknown. In correlation with PTH-induced Bad dephosphorylation, the hormone also decreases the basal association of 14-3-3 and Bad. Overall, our data suggest that in Caco-2 cells, PP2A and the cAMP pathway act in concert to inactivate the AKT survival pathway in PTH-induced intestinal cell apoptosis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0006-3002
pubmed:author
pubmed:copyrightInfo
Copyright 2009 Elsevier B.V. All rights reserved.
pubmed:issnType
Print
pubmed:volume
1803
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
343-51
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
PTH inactivates the AKT survival pathway in the colonic cell line Caco-2.
pubmed:affiliation
Department Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, San Juan 670, (8000) Bahía Blanca, Argentina.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't