Abstract
Current evidences indicate that T cells use protein sorting and degradation to control duration and specificity of T cell receptor (TcR) signalling, including the CD3zeta chain which is ubiquitinated upon TcR triggering. In a previous study, we showed that the Linker of activated T cells (LAT) is present at the plasma membrane and in transferrin-labelled intracellular compartments also containing the CD3zeta chain. Here we show that LAT protein levels are tightly regulated in Jurkat lymphoid T cells likely involving proteasome-dependent degradation, recycling through trans-Golgi/endosome compartments and clathrin-dependent internalisation. We further identify a novel post-translational modification of LAT by ubiquitination that is likely to influence LAT protein stability, intracellular localisation and/or recycling. Our results provide novel molecular and regulatory insights into the function of LAT adapter protein in T cell signalling.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / chemistry
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / metabolism*
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Amino Acid Sequence
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Animals
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Base Sequence
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COS Cells
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Chlorocebus aethiops
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DNA, Complementary / genetics
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Humans
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Jurkat Cells
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Lymphocyte Activation
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Membrane Proteins / chemistry
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Molecular Sequence Data
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Phosphoproteins / chemistry
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Phosphoproteins / genetics
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Phosphoproteins / metabolism*
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Protein Processing, Post-Translational
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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T-Lymphocytes / immunology*
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T-Lymphocytes / metabolism*
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Ubiquitin / metabolism*
Substances
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Adaptor Proteins, Signal Transducing
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DNA, Complementary
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LAT protein, human
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Membrane Proteins
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Phosphoproteins
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Recombinant Fusion Proteins
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Ubiquitin