The role of membrane-associated adaptors in T cell receptor signalling.
Engagement of the T cell receptor leads to activation of several tyrosine kinases and phosphorylation of many intracellular proteins. This is followed by Ca2+ mobilization and activation of multiple biochemical pathways, including the Ras/MAPK cascade, and several downstream serine/threonine kinases. Membrane-associated adaptor proteins play an important role in T cell activation by coupling TCR ligation at the membrane to distal signalling cascades. Several new membrane associated adaptors have been identified in recent years. LAT (linker for activation of T cells) is an adaptor molecule, which following its phosphorylation associates with Grb2, Gads, PLC-gamma 1, and other signalling molecules. The functional importance of this molecule has been demonstrated by the study of LAT-deficient cell lines and LAT-deficient mice. Two other recently identified adaptor proteins, TRIM (T cell receptor interacting molecule) and SIT (SHP2-interacting transmembrane adaptor protein), which constitutively associate with several surface molecules, bind to PI3K and SHP2, respectively, after T cell activation and might also function in the TCR signalling pathway.
Zhang
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Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Samelson
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D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000502:physiology; D051380:GRB2 Adaptor Protein; D006801:Humans; D007527:Isoenzymes / Q000502:physiology; D008213:Lymphocyte Activation / Q000502:physiology; D008565:Membrane Proteins / Q000502:physiology*; D051966:Phospholipase C gamma; D010750:Phosphoproteins / Q000502:physiology; D011506:Proteins / Q000502:physiology; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology*; D010738:Type C Phospholipases / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C409587:GRAP2 protein, human; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; D007527:Isoenzymes; C110810:LAT protein, human; D008565:Membrane Proteins; D010750:Phosphoproteins; D011506:Proteins; D011948:Receptors, Antigen, T-Cell; D018160:Receptors, Cytoplasmic and Nuclear; C114030:TRAT1 protein, human; C099713:nuclear receptor subfamily 0, group B, member 2; D010738:Type C Phospholipases; D051966:Phospholipase C gamma