<?xml version="1.0" encoding="UTF-8" standalone="yes"?> <ProteomeXchangeDataset id="PXD047709" formatVersion="1.4.0" xsi:noNamespaceSchemaLocation="proteomeXchange-1.4.0.xsd" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <CvList> <Cv fullName="PSI-MS" uri="https://raw.githubusercontent.com/HUPO-PSI/psi-ms-CV/master/psi-ms.obo" id="MS"/> <Cv fullName="PSI-MOD" uri="https://raw.githubusercontent.com/MICommunity/psidev/master/psi/mod/data/PSI-MOD.obo" id="MOD"/> <Cv fullName="UNIMOD" uri="http://www.unimod.org/obo/unimod.obo" id="UNIMOD"/> </CvList> <DatasetSummary announceDate="2024-09-14" hostingRepository="PRIDE" title="Quantitative modelling of B cell signaling in aggressive B cell lymphoma"> <Description>The B cell receptor (BCR) signaling, required for the survival and maturation of B cells, is a major deregulated pathway in B cell lymphomas. Several mutations are known to enhance the tonic BCR signal in Burkitt lymphomas (BL) or to mimic an activated receptor in some diffuse large B cell lymphomas (DLBCL). While the proximal events and kinases of the BCR signaling are well studied, less is known about the interactions of downstream effector pathways. In order to reach a less abstract description of this pathway we decided to employ the Modular Response Analysis-based modelling approach STASNet on more directly connected phosphorylation data. Using a Luminex proteomics platform we measured the phosphorylation of fourteen signaling and effector proteins after activating the B cell receptor (BCR) signaling and/or using inhibitors directed against seven intracellular signaling molecules in two independent Burkitt lymphoma cells (BL-2, BL-41). Application of a novel two step STASNet modelling pipeline unveiled novel feedback and crosstalk structures in the BCR-driven signaling network, including a crosstalk from p38 which negatively regulates MEK/ERK-activity in the presence of active BCR. Using Western Blot measurements, we verified and further characterized the p38-MEK/ERK crosstalk and demonstrated that it is a general mechanism in BL cells. Global Tandem Mass Tag (TMT) phosphoproteomic analysis on BL-2 cells found PI3K to be a major mediator of B-cell receptor signaling and manifested the p38-ERK crosstalk directly on ERK phosphosites and indirectly on seven bona fide ERK targets. We also noticed that the BL-2-learned pathway network structure was transferable to perturbation data from closely related BL-41 cells. Moreover, - compared to a literature-derived network - the BL-2-developed predictive pathway proved also to be a better starting point for network development in cells with aberrant BCR signaling in two representative cell lines derived from Diffuse large B cells (HBL-1, OCI-LY3). 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