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 Arbulo-Echevarria, Mikel M
A1 Narbona-Sanchez, Isaac
A1 Fernandez-Ponce, Cecilia M
A1 Vico-Barranco, Inmaculada
A1 Rueda-Ygueravide, Mª Dolores
A1 Dustin, Michael L
A1 Miazek, Arkadiusz
A1 Duran-Ruiz, Mª Carmen
A1 Garcia-Cozar, Francisco
A1 Aguado, Enrique
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 Research Foundation
SN 1664-3224
YR 2018
FD 2018-01-15
LK http://hdl.handle.net/10668/12152
UL http://hdl.handle.net/10668/12152
LA en
NO Arbulo-Echevarria MM, Narbona-Sánchez I, Fernandez-Ponce CM, Vico-Barranco I, Rueda-Ygueravide MD, Dustin ML, et al. 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. Front Immunol. 2018 Feb 2;9:115
DS RISalud
RD Apr 6, 2025