RT journal article
T1 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
A1 Martínez de Arbulo Echevarría, Miguel
A1 Narbona Sánchez,  Isaac
A1 Fernández Ponce, Cecilia Matilde
A1 Vico Barranco, Inmaculada
A1 Rueda-Ygueravide, María Dolores
A1 Dustin, Michael L.
A1 Miazek, Arkadiusz
A1 Durán Ruiz, María del Carmen
A1 García Cózar, Francisco José
A1 Aguado Vidal, Enrique
A2 BiomedicinaBiotecnología y Salud Pública
K1 CD3
K1 LAT
K1 Lck
K1 TCR
K1 signaling
AB 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.
PB FRONTIERS MEDIA SA
SN 1664-3224
YR 2018
FD 2018-02-02
LK http://hdl.handle.net/10498/30352
UL http://hdl.handle.net/10498/30352
LA eng
NO Consejería de Salud de Andalucía, Junta de Andalucía (grants PI-0365-2013 and PI-0055-2017); Instituto de Salud Carlos III (grant PI16-00784 from the “Plan Estatal de I+D+I 2013–2016/FEDER”.
DS Repositorio Institucional de la Universidad de Cádiz
RD 06-nov-2026