SHP-2 expression negatively regulates NK cell function.

The Journal of Immunology : Official Journal of the American Association of Immunologists
Amanda K Purdy, Kerry S Campbell

Abstract

Src homology region 2-containing protein tyrosine phosphatase-2 (SHP-2) is required for full activation of Ras/ERK in many cytokine and growth factor receptor signaling pathways. In contrast, SHP-2 inhibits activation of human NK cells upon recruitment to killer cell Ig-like receptors (KIR). To determine how SHP-2 impacts NK cell activation in KIR-dependent or KIR-independent signaling pathways, we employed knockdown and overexpression strategies in NK-like cell lines and analyzed the consequences on functional responses. In response to stimulation with susceptible target cells, SHP-2-silenced NK cells had elevated cytolytic activity and IFN-gamma production, whereas cells overexpressing wild-type or gain-of-function mutants of SHP-2 exhibited dampened activities. Increased levels of SHP-2 expression over this range significantly suppressed microtubule organizing center polarization and granzyme B release in response to target cells. Interestingly, NK-target cell conjugation was only reduced by overexpressing SHP-2, but not potentiated in SHP-2-silenced cells, indicating that conjugation is not influenced by physiological levels of SHP-2 expression. KIR-dependent inhibition of cytotoxicity was unaffected by significant reductio...Continue Reading

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Citations

Apr 13, 2013·Cell Death and Differentiation·C J ChanL Martinet
Jun 14, 2019·PLoS Pathogens·Tessa Mollie CampbellAllison Abendroth
Jan 29, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·S M Shahjahan MiahKerry S Campbell
Aug 4, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jesús Sánchez-RuizAna González-García
Sep 26, 2020·Frontiers in Endocrinology·Eleni Magdalini Kyritsi, Christina Kanaka-Gantenbein
Sep 23, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Amanda K PurdyKerry S Campbell
Jan 12, 2021·International Immunopharmacology·Khadijeh Dizaji AslHojjatollah Nozad Charoudeh
Mar 5, 2021·Vavilovskiĭ Zhurnal Genetiki I Selekt︠s︡ii·V G SubrakovaA V Taranin

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