Linked Life Data

10553090

Source:http://linkedlifedata.com/resource/pubmed/id/10553090

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1999-12-2
pubmed:abstractText
Sodium salicylate (NaSal) and other nonsteroidal anti-inflammatory drugs (NSAIDs) coordinately inhibit the activity of NF-kappa B, activate heat shock transcription factor 1 and suppress cytokine gene expression in activated monocytes and macrophages. Because our preliminary studies indicated that these effects could be mimicked by inhibitors of signal transduction, we have studied the effects of NSAIDs on signaling molecules potentially downstream of LPS receptors in activated macrophages. Our findings indicate that ribosomal S6 kinase 2 (RSK2), a 90-kDa ribosomal S6 kinase with a critical role as an effector of the RAS-mitogen-activated protein kinase pathway and a regulator of immediate early gene transcription is a target for inhibition by the NSAIDs. NSAIDs inhibited the activity of purified RSK2 kinase in vitro and of RSK2 in mammalian cells and suppressed the phosphorylation of RSK2 substrates cAMP response element binding protein (CREB) and I-kappa B alpha in vivo. Additionally, NaSal inhibited the phosphorylation by RSK2 of CREB and I-kappa B alpha on residues crucial for their transcriptional activity in vivo and thus repressed CREB and NF-kappa B-dependent transcription. These experiments suggest that RSK2 is a target for NSAIDs in the inhibition of monocyte-specific gene expression and indicate the importance of RSK2 and related kinases in cell regulation, indicating a new area for anti-inflammatory drug discovery.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
163
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5608-16
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:10553090-3T3 Cells, pubmed-meshheading:10553090-Animals, pubmed-meshheading:10553090-Anti-Inflammatory Agents, Non-Steroidal, pubmed-meshheading:10553090-Aspirin, pubmed-meshheading:10553090-Cyclic AMP Response Element-Binding Protein, pubmed-meshheading:10553090-Enzyme Activation, pubmed-meshheading:10553090-Enzyme Inhibitors, pubmed-meshheading:10553090-HeLa Cells, pubmed-meshheading:10553090-Humans, pubmed-meshheading:10553090-Interphase, pubmed-meshheading:10553090-Lipopolysaccharides, pubmed-meshheading:10553090-Mice, pubmed-meshheading:10553090-Mitogens, pubmed-meshheading:10553090-Monocytes, pubmed-meshheading:10553090-NF-kappa B, pubmed-meshheading:10553090-Phosphoproteins, pubmed-meshheading:10553090-Phosphorylation, pubmed-meshheading:10553090-Promoter Regions, Genetic, pubmed-meshheading:10553090-Ribosomal Protein S6 Kinases, pubmed-meshheading:10553090-Salicylic Acid, pubmed-meshheading:10553090-Substrate Specificity, pubmed-meshheading:10553090-Transcription, Genetic
pubmed:year
1999
pubmed:articleTitle
Salicylic acid and aspirin inhibit the activity of RSK2 kinase and repress RSK2-dependent transcription of cyclic AMP response element binding protein- and NF-kappa B-responsive genes.
pubmed:affiliation
Department of Adult Oncology, Joint Center for Radiation Therapy, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't