Triomics Analysis of Imatinib-Treated Myeloma Cells Connects Kinase Inhibition to RNA Processing and Decreased Lipid Biosynthesis.

ABSTRACT: The combination of metabolomics, lipidomics, and phosphoproteomics that incorporates triple stable isotope labeling by amino acids in cell culture (SILAC) protein labeling, as well as (13)C in vivo metabolite labeling, was demonstrated on BCR-ABL-positive H929 multiple myeloma cells. From 11 880 phosphorylation sites, we confirm that H929 cells are primarily signaling through the BCR-ABL-ERK pathway, and we show that imatinib treatment not only downregulates phosphosites in this pathway but also upregulates phosphosites on proteins involved in RNA expression. Metabolomics analyses reveal that BCR-ABL-ERK signaling in H929 cells drives the pentose phosphate pathway (PPP) and RNA biosynthesis, where pathway inhibition via imatinib results in marked PPP impairment and an accumulation of RNA n

SUBMITTER: Breitkopf SB 

PROVIDER: S-EPMC5585869 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature