%0 Journal Article
%A Arbulo-Echevarria, Mikel M
%A Narbona-Sanchez, Isaac
%A Fernandez-Ponce, Cecilia M
%A Vico-Barranco, Inmaculada
%A Rueda-Ygueravide, Mª Dolores
%A Dustin, Michael L
%A Miazek, Arkadiusz
%A Duran-Ruiz, Mª Carmen
%A Garcia-Cozar, Francisco
%A Aguado, 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/10668/12152
%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
%~