LymphoAtlas: a dynamic and integrated phosphoproteomic resource of TCR signaling in primary T cells reveals ITSN2 as a regulator of effector functions
Abstract T‐cell receptor (TCR) ligation‐mediated protein phosphorylation regulates the activation, cellular responses, and fates of T cells. Here, we used time‐resolved high‐resolution phosphoproteomics to identify, quantify, and characterize the phosphorylation dynamics of thousands of phosphorylat...
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| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2020-07-01
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| Series: | Molecular Systems Biology |
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| Online Access: | https://doi.org/10.15252/msb.20209524 |
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| author | Marie Locard‐Paulet Guillaume Voisinne Carine Froment Marisa Goncalves Menoita Youcef Ounoughene Laura Girard Claude Gregoire Daiki Mori Manuel Martinez Hervé Luche Jerôme Garin Marie Malissen Odile Burlet‐Schiltz Bernard Malissen Anne Gonzalez de Peredo Romain Roncagalli |
| author_facet | Marie Locard‐Paulet Guillaume Voisinne Carine Froment Marisa Goncalves Menoita Youcef Ounoughene Laura Girard Claude Gregoire Daiki Mori Manuel Martinez Hervé Luche Jerôme Garin Marie Malissen Odile Burlet‐Schiltz Bernard Malissen Anne Gonzalez de Peredo Romain Roncagalli |
| author_sort | Marie Locard‐Paulet |
| collection | DOAJ |
| description | Abstract T‐cell receptor (TCR) ligation‐mediated protein phosphorylation regulates the activation, cellular responses, and fates of T cells. Here, we used time‐resolved high‐resolution phosphoproteomics to identify, quantify, and characterize the phosphorylation dynamics of thousands of phosphorylation sites in primary T cells during the first 10 min after TCR stimulation. Bioinformatic analysis of the data revealed a coherent orchestration of biological processes underlying T‐cell activation. In particular, functional modules associated with cytoskeletal remodeling, transcription, translation, and metabolic processes were mobilized within seconds after TCR engagement. Among proteins whose phosphorylation was regulated by TCR stimulation, we demonstrated, using a fast‐track gene inactivation approach in primary lymphocytes, that the ITSN2 adaptor protein regulated T‐cell effector functions. This resource, called LymphoAtlas, represents an integrated pipeline to further decipher the organization of the signaling network encoding T‐cell activation. LymphoAtlas is accessible to the community at: https://bmm-lab.github.io/LymphoAtlas . |
| format | Article |
| id | doaj-art-b5ae5997a0624969bcd37711bafb3465 |
| institution | Kabale University |
| issn | 1744-4292 |
| language | English |
| publishDate | 2020-07-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-b5ae5997a0624969bcd37711bafb34652024-11-17T12:55:02ZengSpringer NatureMolecular Systems Biology1744-42922020-07-0116711910.15252/msb.20209524LymphoAtlas: a dynamic and integrated phosphoproteomic resource of TCR signaling in primary T cells reveals ITSN2 as a regulator of effector functionsMarie Locard‐Paulet0Guillaume Voisinne1Carine Froment2Marisa Goncalves Menoita3Youcef Ounoughene4Laura Girard5Claude Gregoire6Daiki Mori7Manuel Martinez8Hervé Luche9Jerôme Garin10Marie Malissen11Odile Burlet‐Schiltz12Bernard Malissen13Anne Gonzalez de Peredo14Romain Roncagalli15Institut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse, CNRS, UPSCentre d'Immunologie de Marseille‐Luminy, INSERM, CNRS, Aix Marseille UniversitéInstitut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse, CNRS, UPSCentre d'Immunologie de Marseille‐Luminy, INSERM, CNRS, Aix Marseille UniversitéCentre d'Immunologie de Marseille‐Luminy, INSERM, CNRS, Aix Marseille UniversitéCentre d'Immunologie de Marseille‐Luminy, INSERM, CNRS, Aix Marseille UniversitéCentre d'Immunologie de Marseille‐Luminy, INSERM, CNRS, Aix Marseille UniversitéCentre d'Immunologie de Marseille‐Luminy, INSERM, CNRS, Aix Marseille UniversitéCentre d'Immunophénomique, INSERM, CNRS UMR, Aix Marseille UniversitéCentre d'Immunophénomique, INSERM, CNRS UMR, Aix Marseille UniversitéCEA, BIG, Biologie à Grande Echelle, INSERM, U1038, Université Grenoble‐AlpesCentre d'Immunologie de Marseille‐Luminy, INSERM, CNRS, Aix Marseille UniversitéInstitut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse, CNRS, UPSCentre d'Immunologie de Marseille‐Luminy, INSERM, CNRS, Aix Marseille UniversitéInstitut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse, CNRS, UPSCentre d'Immunologie de Marseille‐Luminy, INSERM, CNRS, Aix Marseille UniversitéAbstract T‐cell receptor (TCR) ligation‐mediated protein phosphorylation regulates the activation, cellular responses, and fates of T cells. Here, we used time‐resolved high‐resolution phosphoproteomics to identify, quantify, and characterize the phosphorylation dynamics of thousands of phosphorylation sites in primary T cells during the first 10 min after TCR stimulation. Bioinformatic analysis of the data revealed a coherent orchestration of biological processes underlying T‐cell activation. In particular, functional modules associated with cytoskeletal remodeling, transcription, translation, and metabolic processes were mobilized within seconds after TCR engagement. Among proteins whose phosphorylation was regulated by TCR stimulation, we demonstrated, using a fast‐track gene inactivation approach in primary lymphocytes, that the ITSN2 adaptor protein regulated T‐cell effector functions. This resource, called LymphoAtlas, represents an integrated pipeline to further decipher the organization of the signaling network encoding T‐cell activation. LymphoAtlas is accessible to the community at: https://bmm-lab.github.io/LymphoAtlas .https://doi.org/10.15252/msb.20209524dynamic biological processesITSN2LymphoAtlasphosphoproteomicsTCR signaling network |
| spellingShingle | Marie Locard‐Paulet Guillaume Voisinne Carine Froment Marisa Goncalves Menoita Youcef Ounoughene Laura Girard Claude Gregoire Daiki Mori Manuel Martinez Hervé Luche Jerôme Garin Marie Malissen Odile Burlet‐Schiltz Bernard Malissen Anne Gonzalez de Peredo Romain Roncagalli LymphoAtlas: a dynamic and integrated phosphoproteomic resource of TCR signaling in primary T cells reveals ITSN2 as a regulator of effector functions Molecular Systems Biology dynamic biological processes ITSN2 LymphoAtlas phosphoproteomics TCR signaling network |
| title | LymphoAtlas: a dynamic and integrated phosphoproteomic resource of TCR signaling in primary T cells reveals ITSN2 as a regulator of effector functions |
| title_full | LymphoAtlas: a dynamic and integrated phosphoproteomic resource of TCR signaling in primary T cells reveals ITSN2 as a regulator of effector functions |
| title_fullStr | LymphoAtlas: a dynamic and integrated phosphoproteomic resource of TCR signaling in primary T cells reveals ITSN2 as a regulator of effector functions |
| title_full_unstemmed | LymphoAtlas: a dynamic and integrated phosphoproteomic resource of TCR signaling in primary T cells reveals ITSN2 as a regulator of effector functions |
| title_short | LymphoAtlas: a dynamic and integrated phosphoproteomic resource of TCR signaling in primary T cells reveals ITSN2 as a regulator of effector functions |
| title_sort | lymphoatlas a dynamic and integrated phosphoproteomic resource of tcr signaling in primary t cells reveals itsn2 as a regulator of effector functions |
| topic | dynamic biological processes ITSN2 LymphoAtlas phosphoproteomics TCR signaling network |
| url | https://doi.org/10.15252/msb.20209524 |
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