Journal
AMERICAN JOURNAL OF PATHOLOGY
Volume 184, Issue 5, Pages 1331-1342Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ajpath.2014.01.036
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Funding
- NIH [RO1 DE119249, RO1 CA136905, RO1 CA140806, R01-CA126239, R01-GM094231]
- Training Program in Bioinformatics [5T32GM070449]
- Fondation pour la Recherche Medicale [SPE20091117389]
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Deregulation of signaling pathways controlled by protein phosphorylation underlies the pathogenesis of hematological malignancies; however, the extent to which deregulated phosphorylation may be involved in B-cell non-Hodgkin lymphoma (B-NHL) pathogenesis is largely unknown. To identify phosphorylation events important in B-NHLs, we performed mass spectrometry based, label-free, semiquantitative phosphoproteomic profiling of 11 cell Lines derived from three B-NHL categories: Burkitt Lymphoma, follicular lymphoma, and mantle-cell Lymphoma. In all, 6579 unique phosphopeptides, corresponding to 1701 unique phosphorylated proteins, were identified and quantified. The data are available via ProteomeXchange with identifier PXD000658. Hierarchical clustering highlighted distinct phosphoproteomic signatures associated with each Lymphoma subtype. Interestingly, germinal center derived B-NHL cell lines were characterized by phosphorylation of proteins involved in the B-cell receptor signaling. Of these proteins, phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (PAG1) was identified with the most phosphorylated tyrosine peptides in Burkitt lymphoma and follicular lymphoma. PAG1 knockdown resulted in perturbation of the tyrosine phosphosignature of B-cell receptor signaling components. Significantly, PAG1 knockdown increased cell proliferation and response to antigen stimulation of these germinal center derived B-NHLs. These data provide a detailed annotation of phosphorylated proteins in human Lymphoid cancer. Overall, our study revealed the utility of unbiased phospho-proteome interrogation in characterizing signaling networks that may provide insights into pathogenesis mechanisms in B-cell lymphomas.
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