title: Differential signaling through p190 and p210 BCR-ABL fusion proteins revealed by interactome and phosphoproteome analysis.
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-ABLand p210BCR-ABLdifferentially 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.
authors.affiliation: Pre-Doctoral Training Program in Human Genetics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|Center for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Cutler
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|Biochemistry, Cellular and Molecular Biology Graduate Program, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: R
authors.initials: R
authors.lastname: Tahir
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|Institute of Bioinformatics, International Technology Park, Bangalore, India.
authors.forename: S K
authors.initials: SK
authors.lastname: Sreenivasamurthy
authors.affiliation: Biochemistry, Cellular and Molecular Biology Graduate Program, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|Ginkgo Bioworks, Boston, MA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Mitchell
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|Center for Proteomics Discovery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: S
authors.initials: S
authors.lastname: Renuse
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|Institute of Bioinformatics, International Technology Park, Bangalore, India.
authors.forename: R S
authors.initials: RS
authors.lastname: Nirujogi
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|Institute of Bioinformatics, International Technology Park, Bangalore, India.|School of Biotechnology, KIIT University, Bhubaneswar, India.
authors.forename: A H
authors.initials: AH
authors.lastname: Patil
authors.affiliation: Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|Center for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: M
authors.initials: M
authors.lastname: Heydarian
authors.affiliation: Laboratory of Developmental and Regenerative Biology, Institute of Medical Biology, Agency for Science, Technology and Research (A∗STAR), Immunos, Singapore.
authors.forename: X
authors.initials: X
authors.lastname: Wong
authors.affiliation: Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: X
authors.initials: X
authors.lastname: Wu
authors.affiliation: Pre-Doctoral Training Program in Human Genetics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|Division of Hematology, Department of Internal Medicine, National Taiwan University and National Taiwan University Cancer Center, Taipei, Taiwan.
authors.forename: T-C
authors.initials: TC
authors.lastname: Huang
authors.affiliation: Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|Department of Applied Chemistry, Kyung Hee University, Yongin, South Korea.
authors.forename: M-S
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|Center for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Reddy
authors.affiliation: Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|Center for Proteomics Discovery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|Departments of Pathology and Oncology, Johns Hopkins, University School of Medicine, Baltimore, MD, USA.
authors.forename: A
authors.initials: A
authors.lastname: Pandey
mesh_terms: D003598:Cytoskeletal Proteins / Q000378:metabolism; D016044:Fusion Proteins, bcr-abl / Q000502:physiology*; D006801:Humans; D007938:Leukemia / Q000209:etiology; D010766:Phosphorylation; D050791:STAT Transcription Factors / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D003598:Cytoskeletal Proteins; D050791:STAT Transcription Factors; D016044:Fusion Proteins, bcr-abl