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Titolo:
The tyrosine kinase PYK-2/RAFTK regulates natural killer (NK) cell cytotoxic response, and is translocated and activated upon specific target cell recognition and killing
Autore:
Sancho, D; Nieto, M; Llano, M; Rodriguez-Fernandez, JL; Tejedor, R; Avraham, S; Cabanas, C; Lopez-Botet, M; Sanchez-Madrid, F;
Indirizzi:
Univ Autonoma Madrid, Serv Inmunol, Hosp Princesa, E-28006 Madrid, Spain Univ Autonoma Madrid Madrid Spain E-28006 rincesa, E-28006 Madrid, Spain Univ Complutense Madrid, Fac Med, Dept Bioquim & Biol Mol, Madrid 28040, Spain Univ Complutense Madrid Madrid Spain 28040 Biol Mol, Madrid 28040, Spain Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Expt Med, Boston, MA 02215 USA Harvard Univ Boston MA USA 02215 Ctr, Div Expt Med, Boston, MA 02215 USA Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA Harvard Univ Boston MA USA 02215 Div Hematol Oncol, Boston, MA 02215 USA
Titolo Testata:
JOURNAL OF CELL BIOLOGY
fascicolo: 6, volume: 149, anno: 2000,
pagine: 1249 - 1261
SICI:
0021-9525(20000612)149:6<1249:TTKPRN>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
FOCAL ADHESION KINASE; CLASS-I MOLECULES; MHC CLASS-I; T-LYMPHOCYTES; INHIBITORY RECEPTORS; SIGNAL-TRANSDUCTION; GAMMA-TUBULIN; PROTEIN; PYK2; PHOSPHORYLATION;
Keywords:
CD94/NKG2; cytotoxicity; microtubule-organizing center; cytoskeletal proteins; HLA-E;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
73
Recensione:
Indirizzi per estratti:
Indirizzo: Sanchez-Madrid, F C Diego de Leon 62, Madrid 28006, Spain C Diego de Leon62 Madrid Spain 28006 rid 28006, Spain
Citazione:
D. Sancho et al., "The tyrosine kinase PYK-2/RAFTK regulates natural killer (NK) cell cytotoxic response, and is translocated and activated upon specific target cell recognition and killing", J CELL BIOL, 149(6), 2000, pp. 1249-1261

Abstract

The compartmentalization of plasma membrane proteins has a key role in regulation of lymphocyte activation and development of immunity. We found thatthe proline-rich tyrosine kinase-2 (PYK-2/RAFTK) colocalized with the microtubule-organizing center (MTOC) at the trailing edge of migrating natural killer (NK) cells. When polyclonal NK cells bound to K562 targets, PYK-2 translocated to the area of NK-target cell interaction. The specificity of this process was assessed with NK cell clones bearing activatory or inhibitory forms of CD94/NKG2, The translocation of PYK-2. MTOC, and paxillin to thearea of NK-target cell contact was regulated upon specific recognition of target cells through NK cell receptors, controlling target cell killing. Furthermore, parallel in vitro kinase assays showed that PYK-2 was activated in response to signals that specifically triggered its translocation and NKcell mediated cytotoxicity. The overexpression of both the wt and a dominant-negative mutant of PYK-2, but not ZAP-70 wt, prevented the specific translocation of the MTOC and paxillin, and blocked the cytotoxic response of NK cells. Our data indicate that subcellular compartmentalization of PYK-2 correlates with effective signal transduction. Furthermore, they also suggest an important role for PYK-2 on the assembly of the signaling complexes that regulate the cytotoxic response.

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Documento generato il 11/07/20 alle ore 06:01:19