RT journal article
T1 Increased Protein Stability and Interleukin-2 Production of a LAT(G131D)Variant With Possible Implications for T Cell Anergy
A1 Martínez de Arbulo Echevarría, Miguel
A1 Vico Barranco, Inmaculada
A1 Narbona Sánchez,  Isaac
A1 García Cózar, Francisco José
A1 Miazek, Arkadiusz
A1 Aguado Vidal, Enrique
A2 BiomedicinaBiotecnología y Salud Pública
K1 LAT
K1 TCR
K1 phosphorylation
K1 anergy
K1 IL-2 (interleukin-2)
AB The adaptor LAT plays a crucial role in the transduction of signals coming from the TCR/CD3 complex. Phosphorylation of some of its tyrosines generates recruitment sites for other cytosolic signaling molecules. Tyrosine 132 in human LAT is essential for PLC-gamma activation and calcium influx generation. It has been recently reported that a conserved glycine residue preceding tyrosine 132 decreases its phosphorylation kinetics, which constitutes a mechanism for ligand discrimination. Here we confirm that a LAT mutant in which glycine 131 has been substituted by an aspartate (LAT(G131D)) increases phosphorylation of Tyr132, PLC-gamma activation and calcium influx generation. Interestingly, the LAT(G131D)mutant has a slower protein turnover while being equally sensitive to Fas-mediated protein cleavage by caspases. Moreover, J.CaM2 cells expressing LAT(G131D)secrete greater amounts of interleukin-2 (IL-2) in response to CD3/CD28 engagement. However, despite this increased IL-2 secretion, J.CaM2 cells expressing the LAT(G131D)mutant are more sensitive to inhibition of IL-2 production by pre-treatment with anti-CD3, which points to a possible role of this residue in the generation of anergy. Our results suggest that the increased kinetics of LAT Tyr132 phosphorylation could contribute to the establishment of T cell anergy, and thus constitutes an earliest known intracellular event responsible for the induction of peripheral tolerance.
PB FRONTIERS MEDIA SA
SN 2296-634X
YR 2020
FD 2020-09
LK http://hdl.handle.net/10498/23941
UL http://hdl.handle.net/10498/23941
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 07-nov-2026