Dataset Information

Functional proteomics defines differential signaling networks of the oncogenic kinases Bcr-Abl p210 and p185

ABSTRACT: The two major isoforms of the oncogenic Bcr-Abl tyrosine kinase, p210 and p185, are expressed upon the Philadelphia chromosome translocation. p210 is the hallmark of chronic myelogenous leukemia, whereas p185 occurs in the majority of B-cell acute lymphoblastic leukemia. Differences in protein-protein interactions and activated signaling pathways that may be associated with the different diseases driven by p210 and p185 are unknown. We have performed a quantitative comparative proteomics study of p210 and p185 and found strong differences in the interactome and phosphoproteome. Whereas the AP2 endocytosis complex interacts preferentially with p185, the phosphatase Sts1 is enriched with p210. Stronger activation of STAT5 and ERK1/2 is observed with p210, whereas Lyn is activated by p185. These results were validated in human p210 and p185-positive cell lines. Our findings contribute to a more coherent understanding of Bcr-Abl signaling, mechanisms of oncogenic transformation, resulting disease pathobiology and responses to kinase inhibitors.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

SUBMITTER: Romain Hamelin

LAB HEAD: Oliver Hantschel

PROVIDER: PXD005149 | Pride | 2017-01-31

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	Interactome_txt.zip	Other
	PhosphoProteome_txt.zip	Other
	SR_150526_Qexactive_IP_S5_01.raw	Raw
	SR_150526_Qexactive_IP_S5_02.raw	Raw
	SR_150526_Qexactive_IP_S5_03.raw	Raw

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Publications

Differential signaling networks of Bcr-Abl p210 and p190 kinases in leukemia cells defined by functional proteomics.

Reckel S S Hamelin R R Georgeon S S Armand F F Jolliet Q Q Chiappe D D Moniatte M M Hantschel O O

Leukemia 20170123 7

The two major isoforms of the oncogenic Bcr-Abl tyrosine kinase, p210 and p190, are expressed upon the Philadelphia chromosome translocation. p210 is the hallmark of chronic myelogenous leukemia, whereas p190 occurs in the majority of B-cell acute lymphoblastic leukemia. Differences in protein interactions and activated signaling pathways that may be associated with the different diseases driven by p210 and p190 are unknown. We have performed a quantitative comparative proteomics study of p210 a ...[more]

PMID: 28111465

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