Historical Background
Engagement of the T cell receptor (TCR) with MHC-peptide complexes leads to the activation of protein tyrosine kinases (PTK), ultimately leading to the activation of downstream signaling events, such as calcium flux and mitogen-activated protein kinase (MAPK) activation (Chan et al. 1994). For many years, it was observed that a 36–38 kDa protein, localized to the plasma membrane, was highly tyrosine phosphorylated upon ligation of the TCR and associated with Grb2, PLC-γ1, and the p85 subunit of PI3K. It was hypothesized that this protein served as a critical link connecting TCR engagement at the membrane to activation of signaling events in the cytosol. In 1998, the gene encoding this protein was identified after microsequencing phosphorylated proteins purified from the membrane fractions of activated Jurkat T cells and was named LAT, linker for activation of Tcells. Sequencing of cDNA clones revealed that LAT is a type III transmembrane protein that contains a...
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Aguado E, Richelme S, Nunez-Cruz S, Miazek A, Mura AM, Richelme M, et al. Induction of T helper type 2 immunity by a point mutation in the LAT adaptor. Science. 2002;296:2036–40.
Brdicka T, Imrich M, Angelisova P, Brdickova N, Horvath O, Spicka J, et al. Non-T cell activation linker (NTAL): a transmembrane adaptor protein involved in immunoreceptor signaling. J Exp Med. 2002;196:1617–26.
Chan AC, Desai DM, Weiss A. The role of protein tyrosine kinases and protein tyrosine phosphatases in T cell antigen receptor signal transduction. Annu Rev Immunol. 1994;12:555–92.
Dong S, Corre B, Foulon E, Dufour E, Veillette A, Acuto O, et al. T cell receptor for antigen induces linker for activation of T cell-dependent activation of a negative signaling complex involving Dok-2, SHIP-1, and Grb-2. J Exp Med. 2006;203:2509–18.
Finco TS, Kadlecek T, Zhang W, Samelson LE, Weiss A. LAT is required for TCR-mediated activation of PLCgamma1 and the Ras pathway. Immunity. 1998;9:617–26.
Hundt M, Tabata H, Jeon MS, Hayashi K, Tanaka Y, Krishna R, et al. Impaired activation and localization of LAT in anergic T cells as a consequence of a selective palmitoylation defect. Immunity. 2006;24:513–22.
Hundt M, Harada Y, De Giorgio L, Tanimura N, Zhang W, Altman A. Palmitoylation-dependent plasma membrane transport but lipid raft-independent signaling by linker for activation of T cells. J Immunol. 2009;183:1685–94.
Janssen E, Zhu M, Zhang W, Koonpaew S. LAB: a new membrane-associated adaptor molecule in B cell activation. Nat Immunol. 2003;4:117–23.
Jordan MS, Singer AL, Koretzky GA. Adaptors as central mediators of signal transduction in immune cells. Nat Immunol. 2003;4:110–6.
Koonpaew S, Shen S, Flowers L, Zhang W. LAT-mediated signaling in CD4+CD25+ regulatory T cell development. J Exp Med. 2006;203:119–29.
Nunez-Cruz S, Aguado E, Richelme S, Chetaille B, Mura AM, Richelme M, et al. LAT regulates gammadelta T cell homeostasis and differentiation. Nat Immunol. 2003;4(10):999–1008.
Saitoh S, Arudchandran R, Manetz TS, Zhang W, Sommers CL, Love PE, et al. LAT is essential for Fc(epsilon)RI-mediated mast cell activation. Immunity. 2000;12:525–35.
Samelson LE. Signal transduction mediated by the T cell antigen receptor: the role of adapter proteins. Annu Rev Immunol. 2002;20:371–94.
Shen S, Zhu M, Lau J, Chuck M, Zhang W. The essential role of LAT in thymocyte development during transition from the double-positive to single-positive stage. J Immunol. 2009;182:5596–604.
Shen S, Chuck MI, Zhu M, Fuller DM, Yang CW, Zhang W. The importance of LAT in the activation, homeostasis, and regulatory function of T cells. J Biol Chem. 2010;285:35393–405.
Sommers CL, Park CS, Lee J, Feng C, Fuller CL, Grinberg A, et al. A LAT mutation that inhibits T cell development yet induces lymphoproliferation. Science. 2002;296:2040–3.
Wang Y, Kissenpfennig A, Mingueneau M, Richelme S, Perrin P, Chevrier S, et al. Th2 lymphoproliferative disorder of LatY136F mutant mice unfolds independently of TCR-MHC engagement and is insensitive to the action of Foxp3+ regulatory T cells. J Immunol. 2008;180:1565–75.
Yamasaki S, Nishida K, Sakuma M, Berry D, McGlade CJ, Hirano T, et al. Gads/Grb2-mediated association with LAT is critical for the inhibitory function of Gab2 in T cells. Mol Cell Biol. 2003;23:2515–29.
Zhang W, Sloan-Lancaster J, Kitchen J, Trible RP, Samelson LE. LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation. Cell. 1998a;92:83–92.
Zhang W, Trible RP, Samelson LE. LAT palmitoylation: its essential role in membrane microdomain targeting and tyrosine phosphorylation during T cell activation. Immunity. 1998b;9:239–46.
Zhang W, Sommers CL, Burshtyn DN, Stebbins CC, DeJarnette JB, Trible RP, et al. Essential role of LAT in T cell development. Immunity. 1999;10:323–32.
Zhang W, Trible RP, Zhu M, Liu SK, McGlade CJ, Samelson LE. Association of Grb2, Gads, and phospholipase C-gamma 1 with phosphorylated LAT tyrosine residues. Effect of LAT tyrosine mutations on T cell angigen receptor-mediated signaling. J Biol Chem. 2000;275:23355–61.
Zhu M, Janssen E, Zhang W. Minimal requirement of tyrosine residues of linker for activation of T cells in TCR signaling and thymocyte development. J Immunol. 2003;170:325–33.
Zhu M, Shen S, Liu Y, Granillo O, Zhang W. Cutting edge: localization of linker for activation of T cells to lipid rafts is not essential in T cell activation and development. J Immunol. 2005;174:31–5.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer International Publishing AG
About this entry
Cite this entry
Sullivan, S., Zhang, W. (2018). LAT. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_7
Download citation
DOI: https://doi.org/10.1007/978-3-319-67199-4_7
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-67198-7
Online ISBN: 978-3-319-67199-4
eBook Packages: Biomedical and Life SciencesReference Module Biomedical and Life Sciences