Differential Signaling Through p190 and p210 BCR-ABL Fusion Proteins Revealed by Interactome and Phosphoproteome Analysis

Leukemia. 2017 Jul;31(7):1513-1524. doi: 10.1038/leu.2017.61. Epub 2017 Feb 17.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cytoskeletal Proteins / metabolism
  • Fusion Proteins, bcr-abl / physiology*
  • Humans
  • Leukemia / etiology
  • Phosphorylation
  • STAT Transcription Factors / physiology
  • Signal Transduction / physiology*

Substances

  • Cytoskeletal Proteins
  • STAT Transcription Factors
  • Fusion Proteins, bcr-abl