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Klinger, B.* ; Rausch, I.* ; Sieber, A.* ; Kutz, H. ; Kruse, V.* ; Kirchner, M.* ; Mertins, P.* ; Kieser, A. ; Blüthgen, N.* ; Kube, D.*

Quantitative modeling of signaling in aggressive B cell lymphoma unveils conserved core network.

PLoS Comput. Biol. 20:e1012488 (2024)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
B cell receptor (BCR) signaling is required for the survival and maturation of B cells and is deregulated in B cell lymphomas. While proximal BCR signaling is well studied, little is known about the crosstalk of downstream effector pathways, and a comprehensive quantitative network analysis of BCR signaling is missing. Here, we semi-quantitatively modelled BCR signaling in Burkitt lymphoma (BL) cells using systematically perturbed phosphorylation data of BL-2 and BL-41 cells. The models unveiled feedback and crosstalk structures in the BCR signaling network, including a negative crosstalk from p38 to MEK/ERK. The relevance of the crosstalk was verified for BCR and CD40 signaling in different BL cells and confirmed by global phosphoproteomics on ERK itself and known ERK target sites. Compared to the starting network, the trained network for BL-2 cells was better transferable to BL-41 cells. Moreover, the BL-2 network was also suited to model BCR signaling in Diffuse large B cell lymphoma cells lines with aberrant BCR signaling (HBL-1, OCI-LY3), indicating that BCR aberration does not cause a major downstream rewiring.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Colon-cancer; Receptor; Feedback; Kinase; Erk; Pathogenesis; Inhibition; Activation; Mechanisms; Expression
ISSN (print) / ISBN 1553-734X
e-ISSN 1553-7358
Zeitschrift PLoS Computational Biology
Quellenangaben Band: 20, Heft: 10, Seiten: , Artikelnummer: e1012488 Supplement: ,
Verlag Public Library of Science (PLoS)
Verlagsort 1160 Battery Street, Ste 100, San Francisco, Ca 94111 Usa
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Gene Vector (AGV)
Research Unit Signaling and Translation (SAT)
Förderungen Bundesinstitut fur Risikobewertung
DKFZ (Young Investigator Grant)
Deutsche Krebshilfe
MSTARS-2
Federal Ministry of Education and Research (BMBF)