Systems‐wide analysis of BCR signalosomes and downstream phosphorylation and ubiquitylation
Abstract B‐cell receptor (BCR) signaling is essential for the development and function of B cells; however, the spectrum of proteins involved in BCR signaling is not fully known. Here we used quantitative mass spectrometry‐based proteomics to monitor the dynamics of BCR signaling complexes (signalos...
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| Format: | Article |
| Language: | English |
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Springer Nature
2015-06-01
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| Series: | Molecular Systems Biology |
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| Online Access: | https://doi.org/10.15252/msb.20145880 |
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| author | Shankha Satpathy Sebastian A Wagner Petra Beli Rajat Gupta Trine A Kristiansen Dessislava Malinova Chiara Francavilla Pavel Tolar Gail A Bishop Bruce S Hostager Chunaram Choudhary |
| author_facet | Shankha Satpathy Sebastian A Wagner Petra Beli Rajat Gupta Trine A Kristiansen Dessislava Malinova Chiara Francavilla Pavel Tolar Gail A Bishop Bruce S Hostager Chunaram Choudhary |
| author_sort | Shankha Satpathy |
| collection | DOAJ |
| description | Abstract B‐cell receptor (BCR) signaling is essential for the development and function of B cells; however, the spectrum of proteins involved in BCR signaling is not fully known. Here we used quantitative mass spectrometry‐based proteomics to monitor the dynamics of BCR signaling complexes (signalosomes) and to investigate the dynamics of downstream phosphorylation and ubiquitylation signaling. We identify most of the previously known components of BCR signaling, as well as many proteins that have not yet been implicated in this system. BCR activation leads to rapid tyrosine phosphorylation and ubiquitylation of the receptor‐proximal signaling components, many of which are co‐regulated by both the modifications. We illustrate the power of multilayered proteomic analyses for discovering novel BCR signaling components by demonstrating that BCR‐induced phosphorylation of RAB7A at S72 prevents its association with effector proteins and with endo‐lysosomal compartments. In addition, we show that BCL10 is modified by LUBAC‐mediated linear ubiquitylation, and demonstrate an important function of LUBAC in BCR‐induced NF‐κB signaling. Our results offer a global and integrated view of BCR signaling, and the provided datasets can serve as a valuable resource for further understanding BCR signaling networks. |
| format | Article |
| id | doaj-art-6e9e558b60ec42e8b4adc1da130fe1df |
| institution | Kabale University |
| issn | 1744-4292 |
| language | English |
| publishDate | 2015-06-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-6e9e558b60ec42e8b4adc1da130fe1df2025-08-20T03:46:32ZengSpringer NatureMolecular Systems Biology1744-42922015-06-0111612210.15252/msb.20145880Systems‐wide analysis of BCR signalosomes and downstream phosphorylation and ubiquitylationShankha Satpathy0Sebastian A Wagner1Petra Beli2Rajat Gupta3Trine A Kristiansen4Dessislava Malinova5Chiara Francavilla6Pavel Tolar7Gail A Bishop8Bruce S Hostager9Chunaram Choudhary10Department of Proteomics, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of CopenhagenDepartment of Proteomics, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of CopenhagenDepartment of Proteomics, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of CopenhagenDepartment of Proteomics, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of CopenhagenDepartment of Proteomics, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of CopenhagenDivision of Immune Cell Biology, MRC National Institute for Medical ResearchDepartment of Proteomics, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of CopenhagenDivision of Immune Cell Biology, MRC National Institute for Medical ResearchDepartment of Microbiology, Graduate Program in Immunology and Department of Internal Medicine, University of IowaDepartment of Pediatrics, University of IowaDepartment of Proteomics, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of CopenhagenAbstract B‐cell receptor (BCR) signaling is essential for the development and function of B cells; however, the spectrum of proteins involved in BCR signaling is not fully known. Here we used quantitative mass spectrometry‐based proteomics to monitor the dynamics of BCR signaling complexes (signalosomes) and to investigate the dynamics of downstream phosphorylation and ubiquitylation signaling. We identify most of the previously known components of BCR signaling, as well as many proteins that have not yet been implicated in this system. BCR activation leads to rapid tyrosine phosphorylation and ubiquitylation of the receptor‐proximal signaling components, many of which are co‐regulated by both the modifications. We illustrate the power of multilayered proteomic analyses for discovering novel BCR signaling components by demonstrating that BCR‐induced phosphorylation of RAB7A at S72 prevents its association with effector proteins and with endo‐lysosomal compartments. In addition, we show that BCL10 is modified by LUBAC‐mediated linear ubiquitylation, and demonstrate an important function of LUBAC in BCR‐induced NF‐κB signaling. Our results offer a global and integrated view of BCR signaling, and the provided datasets can serve as a valuable resource for further understanding BCR signaling networks.https://doi.org/10.15252/msb.20145880BCL10BCRphosphorylationRAB7Aubiquitylation |
| spellingShingle | Shankha Satpathy Sebastian A Wagner Petra Beli Rajat Gupta Trine A Kristiansen Dessislava Malinova Chiara Francavilla Pavel Tolar Gail A Bishop Bruce S Hostager Chunaram Choudhary Systems‐wide analysis of BCR signalosomes and downstream phosphorylation and ubiquitylation Molecular Systems Biology BCL10 BCR phosphorylation RAB7A ubiquitylation |
| title | Systems‐wide analysis of BCR signalosomes and downstream phosphorylation and ubiquitylation |
| title_full | Systems‐wide analysis of BCR signalosomes and downstream phosphorylation and ubiquitylation |
| title_fullStr | Systems‐wide analysis of BCR signalosomes and downstream phosphorylation and ubiquitylation |
| title_full_unstemmed | Systems‐wide analysis of BCR signalosomes and downstream phosphorylation and ubiquitylation |
| title_short | Systems‐wide analysis of BCR signalosomes and downstream phosphorylation and ubiquitylation |
| title_sort | systems wide analysis of bcr signalosomes and downstream phosphorylation and ubiquitylation |
| topic | BCL10 BCR phosphorylation RAB7A ubiquitylation |
| url | https://doi.org/10.15252/msb.20145880 |
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