Linked Life Data

15226414

Source:http://linkedlifedata.com/resource/pubmed/id/15226414

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2004-9-23
pubmed:abstractText
Activation of the inducible transcription factor nuclear factor kappaB (NF-kappaB) occurs in cells exposed to oxidative stress, and the serine/threonine kinase protein kinase D (PKD) is critical for signal relay to NF-kappaB. We have recently delineated two coordinated events that control PKD activation in response to oxidative stress: phosphorylation at Tyr463 by the tyrosine kinase Abl, and phosphorylation at the activation loop Ser738/Ser742 by the protein kinase C (PKC) isoform PKCdelta. The result is fully active PKD that controls NF-kappaB activation through the IkappaB kinase (IKK) complex. Here, we investigate the mechanism by which PKD controls IKK/NF-kappaB activation. Resveratrol, a potent antioxidant, blocks both PKD activation and NF-kappaB induction. In particular, resveratrol blocked PKD activation loop phosphorylation and activity, and this was caused by a specific inhibition of the Ser738/Ser742 kinase PKCdelta. On the other hand, resveratrol did not affect Abl kinase activity and had no effect on Tyr463 phosphorylation. Moreover, we show that the mechanism by which resveratrol inhibits NF-kappaB is by blocking the translocation of PKD to the IKK complex, specifically by inhibiting Ser738/Ser742 phosphorylation. We therefore propose that rather than acting as an antioxidant, resveratrol specifically blocks oxidative stress-dependent NF-kappaB activation by interfering with PKD phosphorylation and association with the IKK complex.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
66
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
870-9
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Activation loop phosphorylation controls protein kinase D-dependent activation of nuclear factor kappaB.
pubmed:affiliation
Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't