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Differential signaling through p190 and p210 BCR-ABL fusion proteins revealed by interactome and phosphoproteome analysis.
Cutler, J A; Tahir, R; Sreenivasamurthy, S K; Mitchell, C; Renuse, S; Nirujogi, R S; Patil, A H; Heydarian, M; Wong, X; Wu, X; Huang, T-C; Kim, M-S; Reddy, K L; Pandey, A.
Afiliación
  • Cutler JA; Pre-Doctoral Training Program in Human Genetics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Tahir R; Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Sreenivasamurthy SK; Center for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Mitchell C; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Renuse S; Biochemistry, Cellular and Molecular Biology Graduate Program, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Nirujogi RS; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Patil AH; Institute of Bioinformatics, International Technology Park, Bangalore, India.
  • Heydarian M; Biochemistry, Cellular and Molecular Biology Graduate Program, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Wong X; Ginkgo Bioworks, Boston, MA, USA.
  • Wu X; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Huang TC; Center for Proteomics Discovery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Kim MS; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Reddy KL; Institute of Bioinformatics, International Technology Park, Bangalore, India.
  • Pandey A; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Leukemia ; 31(7): 1513-1524, 2017 07.
Article en En | MEDLINE | ID: mdl-28210003
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Proteínas de Fusión bcr-abl Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Humans Idioma: En Revista: Leukemia Asunto de la revista: HEMATOLOGIA / NEOPLASIAS Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Proteínas de Fusión bcr-abl Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Humans Idioma: En Revista: Leukemia Asunto de la revista: HEMATOLOGIA / NEOPLASIAS Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido