English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Elucidation of tonic and activated B-cell receptor signaling in Burkitt's lymphoma provides insights into regulation of cell survival.

MPS-Authors
/persons/resource/persons98150

Corso,  J.
Research Group of Bioanalytical Mass Spectrometry, MPI for Biophysical Chemistry, Max Planck Society;

/persons/resource/persons185577

Pan,  K. T.
Research Group of Bioanalytical Mass Spectrometry, MPI for Biophysical Chemistry, Max Planck Society;

/persons/resource/persons85543

Lenz,  C.
Research Group of Bioanalytical Mass Spectrometry, MPI for Biophysical Chemistry, Max Planck Society;

/persons/resource/persons15947

Urlaub,  H.
Research Group of Bioanalytical Mass Spectrometry, MPI for Biophysical Chemistry, Max Planck Society;

External Resource
Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)

2282853_Suppl_1.pdf
(Supplementary material), 3MB

2282853_Suppl_2.xlsx
(Supplementary material), 4MB

2282853_Suppl_3.xlsx
(Supplementary material), 3MB

2282853_Suppl_4.xlsx
(Supplementary material), 3MB

2282853_Suppl_5.docx
(Supplementary material), 17KB

Citation

Corso, J., Pan, K. T., Walter, R., Doebele, C., Mohr, S., Bohnenberger, H., et al. (2016). Elucidation of tonic and activated B-cell receptor signaling in Burkitt's lymphoma provides insights into regulation of cell survival. Proceedings of the National Academy of Sciences of the United States of America, 113(20), 5688-5693. doi:10.1073/pnas.1601053113.


Cite as: http://hdl.handle.net/11858/00-001M-0000-002A-5AA7-0
Abstract
Burkitt's lymphoma (BL) is a highly proliferative B-cell neoplasm and is treated with intensive chemotherapy that, because of its toxicity, is often not suitable for the elderly or for patients with endemic BL in developing countries. BL cell survival relies on signals transduced by B-cell antigen receptors (BCRs). However, tonic as well as activated BCR signaling networks and their relevance for targeted therapies in BL remain elusive. We have systematically characterized and compared tonic and activated BCR signaling in BL by quantitative phosphoproteomics to identify novel BCR effectors and potential drug targets. We identified and quantified ∼16,000 phospho-sites in BL cells. Among these sites, 909 were related to tonic BCR signaling, whereas 984 phospho-sites were regulated upon BCR engagement. The majority of the identified BCR signaling effectors have not been described in the context of B cells or lymphomas yet. Most of these newly identified BCR effectors are predicted to be involved in the regulation of kinases, transcription, and cytoskeleton dynamics. Although tonic and activated BCR signaling shared a considerable number of effector proteins, we identified distinct phosphorylation events in tonic BCR signaling. We investigated the functional relevance of some newly identified BCR effectors and show that ACTN4 and ARFGEF2, which have been described as regulators of membrane-trafficking and cytoskeleton-related processes, respectively, are crucial for BL cell survival. Thus, this study provides a comprehensive dataset for tonic and activated BCR signaling and identifies effector proteins that may be relevant for BL cell survival and thus may help to develop new BL treatments.