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| Item Type: | Article |
|---|---|
| Title: | Quantitative modeling of signaling in aggressive B cell lymphoma unveils conserved core network |
| Creators Name: | Klinger, B., Rausch, I., Siebert, A., Kutz, H., Kruse, V., Kirchner, M., Mertins, P., Kieser, A., Blüthgen, N. and Kube, D. |
| Abstract: | 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. |
| Keywords: | Signaling Networks, Cellular Crosstalk, B Cells, Phosphorylation, Cell Signaling Structures, Network Analysis, Cell Signaling, B Cell Receptors |
| Source: | PLoS Computational Biology |
| ISSN: | 1553-734X |
| Publisher: | Public Library of Science |
| Volume: | 20 |
| Number: | 10 |
| Page Range: | e1012488 |
| Date: | 1 October 2024 |
| Official Publication: | https://doi.org/10.1371/journal.pcbi.1012488 |
| PubMed: | View item in PubMed |
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