LAT palmitoylation: its essential role in membrane microdomain targeting and tyrosine phosphorylation during T cell activation.
The linker molecule LAT is a critical substrate of the tyrosine kinases activated upon TCR engagement. Phosphorylated LAT binds Grb2, PLC-gamma1, and other signaling molecules. We demonstrate that human LAT is palmitoylated and that palmitoylated LAT predominantly localizes into glycolipid-enriched microdomains (GEMs). Although the LAT transmembrane domain is sufficient for membrane localization, palmitoylation at C26 and C29 is essential for efficient partitioning into GEMs. LAT palmitoylation is necessary for its tyrosine phosphorylation. After T cell activation, most tyrosine-phosphorylated LAT molecules and a fraction of PLC-gamma1 and other signaling molecules are present in GEMs. LAT is central to T cell activation and is a novel linker molecule shown to require targeting to membrane microdomains for signaling.
Zhang
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Section on Lymphocyte Signaling, Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-5430, USA.
Trible
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RP
Samelson
L E
LE
D048868:Adaptor Proteins, Signal Transducing; D019943:Amino Acid Substitution / Q000502:physiology; D002352:Carrier Proteins / Q000737:chemistry / Q000502:physiology*; D003545:Cysteine / Q000235:genetics; D006017:Glycolipids; D006801:Humans; D019169:Jurkat Cells / Q000276:immunology / Q000502:physiology; D008213:Lymphocyte Activation / Q000502:physiology; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics; D009154:Mutation / Q000502:physiology; D010168:Palmitates / Q000378:metabolism*; D010750:Phosphoproteins / Q000737:chemistry / Q000502:physiology*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D014443:Tyrosine / Q000737:chemistry
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D006017:Glycolipids; C110810:LAT protein, human; D008565:Membrane Proteins; D010168:Palmitates; D010750:Phosphoproteins; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D003545:Cysteine