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dc.contributor.authorPierce, Andrew
dc.contributor.authorUnwin, Richard D
dc.contributor.authorEvans, Caroline A
dc.contributor.authorGriffiths, Stephen D
dc.contributor.authorCarney, Louise
dc.contributor.authorZhang, Liqun
dc.contributor.authorJaworska, Ewa
dc.contributor.authorLee, Chia-Fang
dc.contributor.authorBlinco, David
dc.contributor.authorOkoniewski, Michal J
dc.contributor.authorMiller, Crispin J
dc.contributor.authorBitton, Danny A
dc.contributor.authorSpooncer, Elaine
dc.contributor.authorWhetton, Anthony D
dc.date.accessioned2009-03-12T17:19:42Z
dc.date.available2009-03-12T17:19:42Z
dc.date.issued2008-05
dc.identifier.citationEight-channel iTRAQ enables comparison of the activity of six leukemogenic tyrosine kinases. 2008, 7 (5):853-63 Mol. Cell Proteomicsen
dc.identifier.issn1535-9484
dc.identifier.pmid17951628
dc.identifier.doi10.1074/mcp.M700251-MCP200
dc.identifier.urihttp://hdl.handle.net/10541/55053
dc.description.abstractThere are a number of leukemogenic protein-tyrosine kinases (PTKs) associated with leukemic transformation. Although each is linked with a specific disease their functional activity poses the question whether they have a degree of commonality in their effects upon target cells. Exon array analysis of the effects of six leukemogenic PTKs (BCR/ABL, TEL/PDGFRbeta, FIP1/PDGFRalpha, D816V KIT, NPM/ALK, and FLT3ITD) revealed few common effects on the transcriptome. It is apparent, however, that proteome changes are not directly governed by transcriptome changes. Therefore, we assessed and used a new generation of iTRAQ tagging, enabling eight-channel relative quantification discovery proteomics, to analyze the effects of these six leukemogenic PTKs. Again these were found to have disparate effects on the proteome with few common targets. BCR/ABL had the greatest effect on the proteome and had more effects in common with FIP1/PDGFRalpha. The proteomic effects of the four type III receptor kinases were relatively remotely related. The only protein commonly affected was eosinophil-associated ribonuclease 7. Five of six PTKs affected the motility-related proteins CAPG and vimentin, although this did not correspond to changes in motility. However, correlation of the proteomics data with that from the exon microarray not only showed poor levels of correlation between transcript and protein levels but also revealed alternative patterns of regulation of the CAPG protein by different oncogenes, illustrating the utility of such a combined approach.
dc.language.isoenen
dc.subjectiTRAQen
dc.subjectLeukemogenic Tyrosine Kinasesen
dc.subjectLukaemia
dc.subject.meshAnimals
dc.subject.meshCell Line
dc.subject.meshChemotaxis
dc.subject.meshExons
dc.subject.meshGene Expression Profiling
dc.subject.meshLeukemia
dc.subject.meshMass Spectrometry
dc.subject.meshMice
dc.subject.meshOligonucleotide Array Sequence Analysis
dc.subject.meshOncogene Proteins
dc.subject.meshProtein Biosynthesis
dc.subject.meshProtein-Serine-Threonine Kinases
dc.subject.meshProteome
dc.subject.meshProteomics
dc.titleEight-channel iTRAQ enables comparison of the activity of six leukemogenic tyrosine kinases.en
dc.typeArticleen
dc.contributor.departmentStem Cell and Leukaemia Proteomics Laboratory, University of Manchester, Christie Hospital, Kinnaird House, Kinnaird Road, Manchester M204QL, United Kingdom.en
dc.identifier.journalMolecular & Cellular Proteomicsen
html.description.abstractThere are a number of leukemogenic protein-tyrosine kinases (PTKs) associated with leukemic transformation. Although each is linked with a specific disease their functional activity poses the question whether they have a degree of commonality in their effects upon target cells. Exon array analysis of the effects of six leukemogenic PTKs (BCR/ABL, TEL/PDGFRbeta, FIP1/PDGFRalpha, D816V KIT, NPM/ALK, and FLT3ITD) revealed few common effects on the transcriptome. It is apparent, however, that proteome changes are not directly governed by transcriptome changes. Therefore, we assessed and used a new generation of iTRAQ tagging, enabling eight-channel relative quantification discovery proteomics, to analyze the effects of these six leukemogenic PTKs. Again these were found to have disparate effects on the proteome with few common targets. BCR/ABL had the greatest effect on the proteome and had more effects in common with FIP1/PDGFRalpha. The proteomic effects of the four type III receptor kinases were relatively remotely related. The only protein commonly affected was eosinophil-associated ribonuclease 7. Five of six PTKs affected the motility-related proteins CAPG and vimentin, although this did not correspond to changes in motility. However, correlation of the proteomics data with that from the exon microarray not only showed poor levels of correlation between transcript and protein levels but also revealed alternative patterns of regulation of the CAPG protein by different oncogenes, illustrating the utility of such a combined approach.


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