Cutting edge: Functional role for proline-rich tyrosine kinase 2 in NK cell-mediated natural cytotoxicity

被引:49
作者
Gismondi, A
Jacobelli, J
Mainiero, F
Paolini, R
Piccoli, M
Frati, L
Santoni, A
机构
[1] Univ Roma La Sapienza, Dept Expt Med & Pathol, Ist Pasteur, Fdn Cenci Bolognetti, I-00161 Rome, Italy
[2] Mediterranean Inst Neurosci, Pozzilli, Italy
关键词
D O I
10.4049/jimmunol.164.5.2272
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Protein tyrosine kinase activation is one of the first biochemical events in the signaling pathway leading to activation of NK cell cytolytic machinery. Here we investigated whether proline-rich tyrosine kinase 2 (Pyk2), the nonreceptor protein tyrosine kinase belonging to the focal adhesion kinase family, could play a role in NR cell-mediated cytotoxicity. Our results demonstrate that binding of NK cells to sensitive target cells or ligation of beta(2) integrins results in a rapid induction of Pyk2 phosphorylation and activation. By contrast, no detectable Pyk2 tyrosine phosphorylation is found upon CD16 stimulation mediated by either mAb or interaction with Ab-coated P815 cells. A functional role for Pyk2 in natural but not Ab-mediated cytotoxicity was demonstrated by the use of recombinant vaccinia viruses encoding the kinase dead mutant of Pyk2. Finally, we provide evidence that Pyk2 is involved in the beta(2) integrin-triggered extracellular signal-regulated kinase activation, supporting the hypothesis that Pyk2. plays a role in the natural cytotoxicity by controlling extracellular signal-regulated kinase activation.
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页码:2272 / 2276
页数:5
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