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LAT, the Linker for Activation of T Cells: A Bridge Between T Cell-Specific and General Signaling Pathways

One of the unresolved questions in T cell receptor (TCR) signaling has been how T cell-specific, TCR-proximal signaling events, such as the activation of the protein tyrosine kinases (PTKs) Lck, Fyn, ZAP-70, Itk, and Tec, lead to the activation of distal, more general signaling elements, such as phospholipase C-γ1 (PLC-γ1), Ras, and phosphatidylinositol 3-kinase (PI3K). With the discovery of LAT, we are much closer to understanding how this occurs. LAT is a 36-kD transmembrane protein that is targeted to lipid rafts and is rapidly tyrosine-phosphorylated after TCR stimulation. LAT appears to serve as a hub between the proximal and distal TCR signaling pathways by facilitating the formation of multimolecular signaling complexes in response to the activation of TCR-associated PTKs. These LAT-assembled complexes are probably involved in ordering interacting proteins into a favorable geometry for productive interaction with one another. In addition to serving as an organizing nucleation scaffold, LAT also serves to localize multiple cytosolic signaling proteins to lipid rafts. Recruitment of signaling proteins to the lipid rafts leads to a very high effective local concentration of these proteins relative to each other, facilitating the formation of additional protein-protein interactions and enhancing enzymatic reaction rates. In addition, LAT-mediated targeting to the lipid rafts may serve to localize enzymes, such as PLC-γ1, PI3K, and SOS, to the vicinity of their substrates. Although it remains to be determined how much of a contribution each of these potential mechanisms makes toward LAT's signal transduction capabilities, the discovery and characterization of LAT has considerably advanced our understanding of the ever more complex series of biochemical events that link TCR engagement with T cell activation.

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Resource Type: Bibliography, Diagram, Illustration, Journal article/Issue, Review, Table
Audience Level: Undergraduate upper division 15-16, Graduate, Professional (degree program)

Author and Copyright

Authors and Editors: Ronald L. Wange of Laboratory of Biological Chemistry, National Institute on Aging
Publisher: American Association for the Advancement of Science
Format: application/pdf, image/gif, image/jpeg, text/html
Copyright and other restrictions: Yes
Cost: Yes


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