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Title

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.

AuthorsSancho, David; Nieto, Marta; Llano, Manuel; Rodríguez-Fernández, José Luis ; Tejedor, Reyes; Avraham, Shalom; Cabañas, Carlos ; López-Botet, Miguel; Sánchez-Madrid, Francisco
KeywordsCD94/NKG2
Cytotoxicity
Microtubule- organizing center
Cytoskeletal proteins
HLA-E
Issue Date12-Jun-2000
PublisherRockefeller University Press
CitationJ Cell Biol. 149(6):1249-62 (2000)
AbstractThe compartmentalization of plasma membrane proteins has a key role in regulation of lymphocyte activation and development of immunity. We found that the 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 the area 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 NK cell 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.
Description13 p.-8 fig.-1 tab.
Publisher version (URL)http://dx.doi.org/ 10.1083/jcb.149.6.1249
URIhttp://hdl.handle.net/10261/135416
DOI10.1083/jcb.149.6.1249
ISSN0021-9525
E-ISSN1540-8140
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