Proteomics

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Integrative proteomics and phosphoproteomics profiling and systems biology analysis reveal dynamic signaling networks and mTORC1-dependent mitochondrial function in T cell activation


ABSTRACT: The underlying mechanisms by which naïve T cells exit from quiescence after antigen stimulation remain elusive. Using multiplex isobaric labeling proteomics technology, we report unbiased, temporal profiling of whole proteome (>8,000 proteins) and phosphoproteome (>13,000 phosphopeptides) during the activation in the wild type and Rptor-/- T cells. TCR stimulation results in dynamic reprogramming of the proteome and phosphoproteome, with predominant upregulation of molecular machineries in protein translation and mitochondrial activation. Loss of mTORC1 disrupts TCR-induced mitochondrial functions including mitoribosome biogenesis, one-carbon metabolism and oxidative phosphorylation.

INSTRUMENT(S): LTQ Orbitrap Elite, Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): T Cell

SUBMITTER: xusheng wang  

LAB HEAD: Junmin Peng

PROVIDER: PXD004367 | Pride | 2017-03-15

REPOSITORIES: Pride

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Publications

Integrative Proteomics and Phosphoproteomics Profiling Reveals Dynamic Signaling Networks and Bioenergetics Pathways Underlying T Cell Activation.

Tan Haiyan H   Yang Kai K   Li Yuxin Y   Shaw Timothy I TI   Wang Yanyan Y   Blanco Daniel Bastardo DB   Wang Xusheng X   Cho Ji-Hoon JH   Wang Hong H   Rankin Sherri S   Guy Cliff C   Peng Junmin J   Chi Hongbo H  

Immunity 20170309 3


The molecular circuits by which antigens activate quiescent T cells remain poorly understood. We combined temporal profiling of the whole proteome and phosphoproteome via multiplexed isobaric labeling proteomics technology, computational pipelines for integrating multi-omics datasets, and functional perturbation to systemically reconstruct regulatory networks underlying T cell activation. T cell receptors activated the T cell proteome and phosphoproteome with discrete kinetics, marked by early d  ...[more]

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