Autor: |
Mikel M. Arbulo-Echevarria, Isaac Narbona-Sánchez, Cecilia M. Fernandez-Ponce, Inmaculada Vico-Barranco, Mª Dolores Rueda-Ygueravide, Michael L. Dustin, Arkadiusz Miazek, Mª Carmen Duran-Ruiz, Francisco García-Cózar, Enrique Aguado |
Jazyk: |
angličtina |
Rok vydání: |
2018 |
Předmět: |
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Zdroj: |
Frontiers in Immunology, Vol 9 (2018) |
Druh dokumentu: |
article |
ISSN: |
1664-3224 |
DOI: |
10.3389/fimmu.2018.00115 |
Popis: |
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. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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