LymphoAtlas: a dynamic and integrated phosphoproteomic resource ofTCRsignaling in primary T cells revealsITSN2 as a regulator of effector functions

Research output: Contribution to journalJournal articleResearchpeer-review

  • Locard-Paulet, Marie
  • Guillaume Voisinne
  • Carine Froment
  • Marisa Goncalves Menoita
  • Youcef Ounoughene
  • Laura Girard
  • Claude Gregoire
  • Daiki Mori
  • Manuel Martinez
  • Herve Luche
  • Jerome Garin
  • Marie Malissen
  • Odile Burlet-Schiltz
  • Bernard Malissen
  • Anne Gonzalez de Peredo
  • Romain Roncagalli

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 afterTCRstimulation. 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 afterTCRengagement. Among proteins whose phosphorylation was regulated byTCRstimulation, we demonstrated, using a fast-track gene inactivation approach in primary lymphocytes, that theITSN2 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: .

Original languageEnglish
Article number9524
JournalMolecular Systems Biology
Volume16
Issue number7
Number of pages19
ISSN1744-4292
DOIs
Publication statusPublished - Jul 2020
Externally publishedYes

    Research areas

  • dynamic biological processes, ITSN2, LymphoAtlas, phosphoproteomics, TCRsignaling network, GROWTH-FACTOR RECEPTOR, ACTIN POLYMERIZATION, PHOSPHORYLATION, ACTIVATION, KINASES, UBIQUITYLATION, AFFINITY, PATHWAY, ZAP-70, CBL

ID: 250122917