Linked Life Data

16687476

Source:http://linkedlifedata.com/resource/pubmed/id/16687476

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2006-7-14
pubmed:abstractText
Therapeutic strategies focused on kinase inhibition rely heavily on surrogate measures of kinase inhibition obtained from in vitro assay systems. There is a need to develop methodology that will facilitate measurement of kinase inhibitor activity or specificity in tissue samples from whole animals treated with these compounds. Many of the current methods are limited by the use of antibodies, many of which do not cross-react between several species. The proteomics approach described herein has the potential to reveal novel tissue substrates, potential new pathway interconnections, and inhibitor specificity by monitoring differences in protein phosphorylation. We used the protein kinase inhibitor H89 (N-(2-[p-bromocinnamylamino]-ethyl)-5-isoquinolinesulfonamide) as a tool to determine whether differential profiling of tissue phosphoproteins can be used to detect treatment-related effects of a protein kinase A (PKA) inhibitor in vivo. With a combination of phosphoprotein column enrichment, high-throughput two-dimensional gel electrophoresis, differential gel staining with Pro-Q Diamond/SYPRO Ruby, statistical analysis, and matrix-assisted laser desorption ionization/time of flight mass spectrometry analysis, we were able to show clear differences between the phosphoprotein profiles of rat liver protein extract from control and treated animals. Moreover, several proteins that show a potential change in phosphorylation were previously identified as PKA substrates or have putative PKA phosphorylation sites. The data presented support the use of differential proteomic methods to measure effects of kinase inhibitor treatment on protein phosphorylation in vivo.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
318
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
589-95
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:16687476-Animals, pubmed-meshheading:16687476-Cyclic AMP-Dependent Protein Kinases, pubmed-meshheading:16687476-Databases, Genetic, pubmed-meshheading:16687476-Electrophoresis, Gel, Two-Dimensional, pubmed-meshheading:16687476-Enzyme Inhibitors, pubmed-meshheading:16687476-Image Processing, Computer-Assisted, pubmed-meshheading:16687476-Isoquinolines, pubmed-meshheading:16687476-Liver, pubmed-meshheading:16687476-Male, pubmed-meshheading:16687476-Phosphoproteins, pubmed-meshheading:16687476-Phosphorylation, pubmed-meshheading:16687476-Protein Kinase Inhibitors, pubmed-meshheading:16687476-Proteomics, pubmed-meshheading:16687476-Rats, pubmed-meshheading:16687476-Rats, Sprague-Dawley, pubmed-meshheading:16687476-Spectrometry, Mass, Matrix-Assisted Laser..., pubmed-meshheading:16687476-Sulfonamides
pubmed:year
2006
pubmed:articleTitle
Proteomic analysis of rat liver phosphoproteins after treatment with protein kinase inhibitor H89 (N-(2-[p-bromocinnamylamino-]ethyl)-5-isoquinolinesulfonamide).
pubmed:affiliation
Toxicology and Drug Disposition, Lilly Research Laboratories, Eli Lilly and Company, Greenfield, IN 46140, USA. davisma@lilly.com
pubmed:publicationType
Journal Article