RT journal article
T1 Non-T cell activation linker (NTAL) proteolytic cleavage as a terminator of activatory intracellular signals
A1 Martínez de Arbulo Echevarría, Miguel
A1 Muñoz Miranda, Juan Pedro
A1 Caballero-García, Andrés
A1 Poveda-Díaz, José L
A1 Fernández Ponce, Cecilia Matilde
A1 Durán Ruiz, María del Carmen
A1 Miazek, Arkadiusz
A1 García Cózar, Francisco José
A1 Aguado Vidal, Enrique
A2 BiomedicinaBiotecnología y Salud Pública
K1 signal transduction
K1 B lymphocytes, monocyte
K1 LAT2
K1 caspases
AB Non-T cell activation linker is an adaptor protein that istyrosine phosphorylated upon cross-linking of immunereceptors expressed on B lymphocytes, NK cells, macrophages,basophils, or mast cells, allowing the recruitmentof cytosolic mediators for downstream signalingpathways. Fas receptor acts mainly as a death receptor,and when cross-linked with Fas ligand, many proteinsare proteolytically cleaved, including several signalingmolecules in T and B cells. Fas receptor triggering alsointerferes with TCR intracellular signals, probably bymeans of proteolytic cleavage of several adaptor proteins.We have previously found that the adaptor linkerfor activation of T cells, evolutionarily related to non-T cellactivation linker, is cleaved upon proapoptotic stimuliin T lymphocytes and thymocytes, in a tyrosinephosphorylation-dependent fashion. Here, we describenon-T cell activation linker proteolytic cleavage triggeredin human B cells and monocytes by Fas cross-linking andstaurosporine treatment. Non-T cell activation linker iscleaved, producing an N-terminal fragment of ;22 kDa,and such cleavage is abrogated in the presence ofcaspase 8/granzyme B and caspase 3 inhibitors. Moreover,we have identified an aspartic acid residue at whichnon-T cell activation linker is cleaved, which similar tolinker for activation of T cells, this aspartic acid residue islocated close to tyrosine and serine residues, suggestingan interdependence of phosphorylation and proteolyticcleavage. Consistently, induction of non-T cellactivation linker phosphorylation by pervanadateinhibits its cleavage. Interestingly, the truncatedisoform of non-T cell activation linker, generated aftercleavage, has a decreased signaling ability whencompared with the full-length molecule. Altogether, ourresults suggest that cleavage of transmembraneadaptors constitutes a general mechanism for signaltermination of immune receptors.
PB WILEY
SN 1938-3673
YR 2016
FD 2016-01-21
LK http://hdl.handle.net/10498/30291
UL http://hdl.handle.net/10498/30291
LA eng
NO 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)
DS Repositorio Institucional de la Universidad de Cádiz
RD 07-nov-2026