title: Cutting edge: functional role for proline-rich tyrosine kinase 2 in NK cell-mediated natural cytotoxicity.
abstract: 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 beta2 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 beta2 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.
authors.affiliation: Department of Experimental Medicine and Pathology, Istituto Pasteur-Fondazione Cenci Bolognetti, University of Rome "La Sapienza"; and Mediterranean Institute of Neuroscience, Neuromed, Pozzilli, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Gismondi
authors.forename: J
authors.initials: J
authors.lastname: Jacobelli
authors.forename: F
authors.initials: F
authors.lastname: Mainiero
authors.forename: R
authors.initials: R
authors.lastname: Paolini
authors.forename: M
authors.initials: M
authors.lastname: Piccoli
authors.forename: L
authors.initials: L
authors.lastname: Frati
authors.forename: A
authors.initials: A
authors.lastname: Santoni
mesh_terms: D000920:Antibody-Dependent Cell Cytotoxicity; D018821:CD18 Antigens / Q000378:metabolism; D002448:Cell Adhesion / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D004789:Enzyme Activation / Q000276:immunology; D004790:Enzyme Induction / Q000276:immunology; D051418:Focal Adhesion Kinase 2; D006801:Humans; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D017452:Receptors, IgG / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D014443:Tyrosine / Q000378:metabolism
chemical_list: D018821:CD18 Antigens; D017452:Receptors, IgG; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D051418:Focal Adhesion Kinase 2