TY - JOUR TI - CD56 regulates human NK cell cytotoxicity through Pyk2 AU - Gunesch, Justin T AU - Dixon, Amera L AU - Ebrahim, Tasneem AM AU - Berrien-Elliott, Melissa M AU - Tatineni, Swetha AU - Kumar, Tejas AU - Hegewisch-Solloa, Everardo AU - Fehniger, Todd A AU - Mace, Emily M A2 - Dustin, Michael L A2 - Akhmanova, Anna A2 - Dustin, Michael L VL - 9 PY - 2020 DA - 2020/06/08 SP - e57346 C1 - eLife 2020;9:e57346 DO - 10.7554/eLife.57346 UR - https://doi.org/10.7554/eLife.57346 AB - Human natural killer (NK) cells are defined as CD56+CD3−. Despite its ubiquitous expression on human NK cells the role of CD56 (NCAM) in human NK cell cytotoxic function has not been defined. In non-immune cells, NCAM can induce signaling, mediate adhesion, and promote exocytosis through interactions with focal adhesion kinase (FAK). Here we demonstrate that deletion of CD56 on the NK92 cell line leads to impaired cytotoxic function. CD56-knockout (KO) cells fail to polarize during immunological synapse (IS) formation and have severely impaired exocytosis of lytic granules. Phosphorylation of the FAK family member Pyk2 at tyrosine 402 is decreased in NK92 CD56-KO cells, demonstrating a functional link between CD56 and signaling in human NK cells. Cytotoxicity, lytic granule exocytosis, and the phosphorylation of Pyk2 are rescued by the reintroduction of CD56. These data highlight a novel functional role for CD56 in stimulating exocytosis and promoting cytotoxicity in human NK cells. KW - natural killer cells KW - cytotoxicity KW - innate immunity KW - NCAM JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -