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

ABSTRACT: 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 and p190. Strong differences in the interactome and tyrosine phosphoproteome were found and validated. Whereas the AP2 adaptor complex that regulates clathrin-mediated endocytosis interacts preferentially with p190, the phosphatase Sts1 is enriched with p210. Stronger activation of the Stat5 transcri

SUBMITTER: Reckel S 

PROVIDER: S-EPMC5508078 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature