RT Journal Article
T1 Increased Protein Stability and Interleukin-2 Production of a LATG131D Variant With Possible Implications for T Cell Anergy.
A1 Arbulo-Echevarria, Mikel M
A1 Vico-Barranco, Inmaculada
A1 Narbona-Sanchez, Isaac
A1 Garcia-Cozar, Francisco
A1 Miazek, Arkadiusz
A1 Aguado, Enrique
K1 IL-2 (interleukin-2)
K1 LAT
K1 TCR
K1 Anergy
K1 Phosphorylation
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-γ 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 (LATG131D) increases phosphorylation of Tyr132, PLC-γ activation and calcium influx generation. Interestingly, the LATG131D mutant has a slower protein turnover while being equally sensitive to Fas-mediated protein cleavage by caspases. Moreover, J.CaM2 cells expressing LATG131D 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 LATG131D 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 Research Foundation
SN 2296-634X
YR 2020
FD 2020-08-13
LK http://hdl.handle.net/10668/16400
UL http://hdl.handle.net/10668/16400
LA en
NO Arbulo-Echevarria MM, Vico-Barranco I, Narbona-Sánchez I, García-Cózar F, Miazek A, Aguado E. Increased Protein Stability and Interleukin-2 Production of a LATG131D Variant With Possible Implications for T Cell Anergy. Front Cell Dev Biol. 2020 Sep 11;8:561503
DS RISalud
RD Sep 23, 2025