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

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

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Two major types of leukemogenic BCR-ABL fusion proteins are p190 BCR-ABL and p210 BCR-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 p190 BCR-ABL and p210 BCR-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 p210 BCR-ABL , we observed an increased engagement of molecules active proximal to the membrane and in the case of p190 BCR-ABL , an engagement of molecules of the cytoskeleton. These differences in signaling could underlie the distinct leukemogenic process induced by these two protein variants.

Original languageEnglish (US)
Pages (from-to)1513-1524
Number of pages12
JournalLeukemia
Volume31
Issue number7
DOIs
StatePublished - Jul 1 2017

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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