@misc{10498/30291,
year = {2016},
month = {1},
url = {http://hdl.handle.net/10498/30291},
abstract = {Non-T cell activation linker is an adaptor protein that is
tyrosine phosphorylated upon cross-linking of immune
receptors expressed on B lymphocytes, NK cells, macrophages,
basophils, or mast cells, allowing the recruitment
of cytosolic mediators for downstream signaling
pathways. Fas receptor acts mainly as a death receptor,
and when cross-linked with Fas ligand, many proteins
are proteolytically cleaved, including several signaling
molecules in T and B cells. Fas receptor triggering also
interferes with TCR intracellular signals, probably by
means of proteolytic cleavage of several adaptor proteins.
We have previously found that the adaptor linker
for activation of T cells, evolutionarily related to non-T cell
activation linker, is cleaved upon proapoptotic stimuli
in T lymphocytes and thymocytes, in a tyrosine
phosphorylation-dependent fashion. Here, we describe
non-T cell activation linker proteolytic cleavage triggered
in human B cells and monocytes by Fas cross-linking and
staurosporine treatment. Non-T cell activation linker is
cleaved, producing an N-terminal fragment of ;22 kDa,
and such cleavage is abrogated in the presence of
caspase 8/granzyme B and caspase 3 inhibitors. Moreover,
we have identified an aspartic acid residue at which
non-T cell activation linker is cleaved, which similar to
linker for activation of T cells, this aspartic acid residue is
located close to tyrosine and serine residues, suggesting
an interdependence of phosphorylation and proteolytic
cleavage. Consistently, induction of non-T cell
activation linker phosphorylation by pervanadate
inhibits its cleavage. Interestingly, the truncated
isoform of non-T cell activation linker, generated after
cleavage, has a decreased signaling ability when
compared with the full-length molecule. Altogether, our
results suggest that cleavage of transmembrane
adaptors constitutes a general mechanism for signal
termination of immune receptors.},
organization = {Consejería de Salud de Andalucía, Junta de Andalucía (Spain) (PI-0365-2013); Consejería de Economía, Innovacíon y Ciencia, Junta de Andalucía (España) (P08-CTS-04348); MICINN (España) (SAF2009-09449); Polish National Science Centre (Poland) (2012/05/B/NZ5/01339);Instituto Nacional de Salud Carlos III (PI12- 02680)},
publisher = {WILEY},
keywords = {signal transduction},
keywords = {B lymphocytes, monocyte},
keywords = {LAT2},
keywords = {caspases},
title = {Non-T cell activation linker (NTAL) proteolytic cleavage as a terminator of activatory intracellular signals},
doi = {10.1189/jlb.2A0715-318R},
author = {Martínez de Arbulo Echevarría, Miguel and Muñoz Miranda, Juan Pedro and Caballero-García, Andrés and Poveda-Díaz, José L and Fernández Ponce, Cecilia Matilde and Durán Ruiz, María del Carmen and Miazek, Arkadiusz and García Cózar, Francisco José and Aguado Vidal, Enrique},
}