Eight-channel iTRAQ enables comparison of the activity of six leukemogenic tyrosine kinases.
Unwin, Richard D
Evans, Caroline A
Griffiths, Stephen D
Okoniewski, Michal J
Miller, Crispin J
Bitton, Danny A
Whetton, Anthony D
AffiliationStem Cell and Leukaemia Proteomics Laboratory, University of Manchester, Christie Hospital, Kinnaird House, Kinnaird Road, Manchester M204QL, United Kingdom.
MetadataShow full item record
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.
CitationEight-channel iTRAQ enables comparison of the activity of six leukemogenic tyrosine kinases. 2008, 7 (5):853-63 Mol. Cell Proteomics
JournalMolecular & Cellular Proteomics
- Targeting PIM kinases impairs survival of hematopoietic cells transformed by kinase inhibitor-sensitive and kinase inhibitor-resistant forms of Fms-like tyrosine kinase 3 and BCR/ABL.
- Authors: Adam M, Pogacic V, Bendit M, Chappuis R, Nawijn MC, Duyster J, Fox CJ, Thompson CB, Cools J, Schwaller J
- Issue date: 2006 Apr 1
- Identification of nuclear protein targets for six leukemogenic tyrosine kinases governed by post-translational regulation.
- Authors: Pierce A, Williamson A, Jaworska E, Griffiths JR, Taylor S, Walker M, Aspinall-O'Dea M, Spooncer E, Unwin RD, Poolman T, Ray D, Whetton AD
- Issue date: 2012
- Quantitative proteomic analysis using isobaric protein tags enables rapid comparison of changes in transcript and protein levels in transformed cells.
- Authors: Unwin RD, Pierce A, Watson RB, Sternberg DW, Whetton AD
- Issue date: 2005 Jul
- Comprehensive mass-spectrometry-based proteome quantification of haploid versus diploid yeast.
- Authors: de Godoy LM, Olsen JV, Cox J, Nielsen ML, Hubner NC, Fröhlich F, Walther TC, Mann M
- Issue date: 2008 Oct 30
- Progressive changes in the leukemogenic signaling in BCR/ABL-transformed cells.
- Authors: Nieborowska-Skorska M, Slupianek A, Skorski T
- Issue date: 2000 Aug 24