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

Angela Gismondi, Jordan Jacobelli, Fabrizio Mainiero, Rossella Paolini, Mario Piccoli, Luigi Frati, Angela Santoni

Research output: Contribution to journalArticlepeer-review


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 NK Cell-mediated cytotoxicity. Our results demonstrate that binding of NK cells to sensitive target cells or ligation of β2 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 β2 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.

Original languageEnglish
Pages (from-to)2272-2276
Number of pages5
JournalJournal of Immunology
Issue number5
Publication statusPublished - Mar 1 2000

ASJC Scopus subject areas

  • Immunology


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