Publication: LymphoAtlas: a dynamic and integrated phosphoproteomic resource of TCR signaling in primary T cells reveals ITSN2 as a regulator of effector functions.

Publié dans: Mol Syst Biol 2020 Jul; 16(7): e9524

Auteurs: Locard-Paulet M, Voisinne G, Froment C, Goncalves Menoita M, Ounoughene Y, Girard L, Gregoire C, Mori D, Martinez M, Luche H, Garin J, Malissen M, Burlet-Schiltz O, Malissen B, Gonzalez de Peredo A, Roncagalli R

Résumé

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.

Lien vers Pubmed [PMID] – 32618424

Lien vers HAL – hal-02981563

Lien vers le DOI – 10.15252/msb.20209524