Differential signaling through p190 and p210 BCR-ABL fusion proteins revealed by interactome and phosphoproteome analysis View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2017-07

AUTHORS

J A Cutler, R Tahir, S K Sreenivasamurthy, C Mitchell, S Renuse, R S Nirujogi, A H Patil, M Heydarian, X Wong, X Wu, T-C Huang, M-S Kim, K L Reddy, A Pandey

ABSTRACT

Two major types of leukemogenic BCR-ABL fusion proteins are p190BCR-ABLand p210BCR-ABL. Although the two fusion proteins are closely related, they can lead to different clinical outcomes. A thorough understanding of the signaling programs employed by these two fusion proteins is necessary to explain these clinical differences. We took an integrated approach by coupling protein-protein interaction analysis using biotinylation identification with global phosphorylation analysis to investigate the differences in signaling between these two fusion proteins. Our findings suggest that p190BCR-ABL and p210BCR-ABL differentially activate important signaling pathways, such as JAK-STAT, and engage with molecules that indicate interaction with different subcellular compartments. In the case of p210BCR-ABL, we observed an increased engagement of molecules active proximal to the membrane and in the case of p190BCR-ABL, an engagement of molecules of the cytoskeleton. These differences in signaling could underlie the distinct leukemogenic process induced by these two protein variants. More... »

PAGES

1513-1524

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/leu.2017.61

    DOI

    http://dx.doi.org/10.1038/leu.2017.61

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1083845461

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/28210003


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