%0 Journal Article 
%A Martínez de Arbulo Echevarría, Miguel
%A Narbona Sánchez,  Isaac
%A Fernández Ponce, Cecilia Matilde
%A Vico Barranco, Inmaculada
%A Rueda-Ygueravide, María Dolores
%A Dustin, Michael L.
%A Miazek, Arkadiusz
%A Durán Ruiz, María del Carmen
%A García Cózar, Francisco José
%A Aguado Vidal, Enrique
%T A Stretch of Negatively Charged Amino Acids of Linker for Activation of T-Cell Adaptor Has a Dual Role in T-Cell Antigen Receptor Intracellular Signaling
%D 2018
%@ 1664-3224
%U http://hdl.handle.net/10498/30352
%X The adaptor protein linker for activation of T cells (LAT) has an essential role transducing activatory intracellular signals coming from the TCR/CD3 complex. Previous reports have shown that upon T-cell activation, LAT interacts with the tyrosine kinase Lck, leading to the inhibition of its kinase activity. LAT-Lck interaction seemed to depend on a stretch of negatively charged amino acids in LAT. Here, we have substituted this segment of LAT between amino acids 113 and 126 with a non-charged segment and expressed the mutant LAT (LAT-NIL) in J.CaM2 cells in order to analyze TCR signaling. Substitution of this segment in LAT prevented the activation-induced interaction with Lck. Moreover, cells expressing this mutant form of LAT showed a statistically significant increase of proximal intracellular signals such as phosphorylation of LAT in tyrosine residues 171 and 191, and also enhanced ZAP70 phosphorylation approaching borderline statistical significance (p = 0.051). Nevertheless, downstream signals such as Ca2+ influx or MAPK pathways were partially inhibited. Overall, our data reveal that LAT-Lck interaction constitutes a key element regulating proximal intracellular signals coming from the TCR/CD3 complex.
%K CD3
%K LAT
%K Lck
%K TCR
%K signaling
%~ Universidad de Cádiz