Related Experiment Video
Updated: Aug 9, 2026

A TIRF Microscopy Technique for Real-time, Simultaneous Imaging of the TCR and its Associated Signaling Proteins
Published on: March 22, 2012
The role of membrane-associated adaptors in T cell receptor signalling
1Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Abstract:
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.
Insights
Membrane-associated adaptor proteins are crucial for T cell activation. LAT (linker for activation of T cells), TRIM (T cell receptor interacting molecule), and SIT (SHP2-interacting transmembrane adaptor protein) are key players in T cell receptor signaling pathways.
Area of Science:
- Immunology
- Molecular Biology
- Cell Signaling
Background:
- T cell receptor (TCR) engagement initiates signaling cascades involving tyrosine kinases and intracellular protein phosphorylation.
- Membrane-associated adaptor proteins are critical for linking TCR ligation to downstream signaling pathways.
- Several novel adaptor proteins have been identified, highlighting their importance in T cell activation.
Purpose of the Study:
- To elucidate the role of membrane-associated adaptor proteins in T cell activation.
- To investigate the function of LAT (linker for activation of T cells) in TCR signaling.
- To explore the potential roles of TRIM (T cell receptor interacting molecule) and SIT (SHP2-interacting transmembrane adaptor protein) in T cell signaling.
Main Methods:
- Study of LAT-deficient cell lines and LAT-deficient mice to assess functional importance.
- Identification and characterization of novel adaptor proteins like TRIM and SIT.
- Analysis of protein-protein interactions and signaling pathway involvement.
Main Results:
- LAT adaptor protein, upon phosphorylation, associates with Grb2, Gads, and PLC-gamma 1, mediating TCR signaling.
- Studies using LAT-deficient models confirm its essential role in T cell activation.
- TRIM and SIT are identified as novel adaptors that associate with PI3K and SHP2, respectively, post-TCR activation.
Conclusions:
- Membrane-associated adaptor proteins, including LAT, TRIM, and SIT, are indispensable for effective T cell receptor signaling.
- LAT plays a central role by recruiting key signaling molecules following TCR engagement.
- TRIM and SIT represent newly discovered components that likely contribute to the intricate TCR signaling network.
Related Concept Videos
Tail-anchoring of Proteins in the ER Membrane
Assembly of Signaling Complexes
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Amplifying Signals via Enzymatic Cascade
Activation of Integrins
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.
Intracellular Signaling Affects Focal Adhesions
Some...
T Cell Activation and Clonal Selection
Naive T cells that have not yet encountered an antigen express two primary CD...

