Eight-channel iTRAQ enables comparison of the activity of six leukemogenic tyrosine kinases.
Authors
Pierce, AndrewUnwin, Richard D
Evans, Caroline A
Griffiths, Stephen D
Carney, Louise
Zhang, Liqun
Jaworska, Ewa
Lee, Chia-Fang
Blinco, David
Okoniewski, Michal J
Miller, Crispin J
Bitton, Danny A
Spooncer, Elaine
Whetton, Anthony D
Affiliation
Stem Cell and Leukaemia Proteomics Laboratory, University of Manchester, Christie Hospital, Kinnaird House, Kinnaird Road, Manchester M204QL, United Kingdom.Issue Date
2008-05
Metadata
Show full item recordAbstract
There 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.Citation
Eight-channel iTRAQ enables comparison of the activity of six leukemogenic tyrosine kinases. 2008, 7 (5):853-63 Mol. Cell ProteomicsJournal
Molecular & Cellular ProteomicsDOI
10.1074/mcp.M700251-MCP200PubMed ID
17951628Type
ArticleLanguage
enISSN
1535-9484ae974a485f413a2113503eed53cd6c53
10.1074/mcp.M700251-MCP200
Scopus Count
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