GTP-binding proteins transduce signals generated via human FCγ receptor IIIA (CD16)

Antonio D G Procopio, Rossella Paolini, Immacolata Vecchio, Luigi Frati, Angela Santoni

Research output: Contribution to journalArticle

Abstract

This study demonstrates that GTP-binding proteins regulate FcγRIII-mediated signal transduction and inositol phosphate (IPn) generation in human NK cells. In addition the cross-linking of CD16 by mAb, guanosine 5′-o-3-thiophosphate induced 1,4,5 inositol trisphosphate (IP3) release in permeabilized NK cells and their membranes. By contrast, guanosine 5′-o-2-thiophosphate, almost completely inhibited IP3 generation induced by cross-linking with anti-CD16 mAb. Pretreatment of NK cells with 10 to 100 ng/m1 Vibrio cholerae toxin (Ctx) almost completely inhibited the generation of IP3 and of other Ipn as well as FcγRIII-operated cell functions such as antibody-dependent cell-mediated cytotoxicity against antibody-coated P815 mastocytoma cells. Isolated B subunit of Ctx was inactive. Bordetella pertussis toxin (0.1 to 1 μg/ml) only marginally affected IP3 release and antibody-dependent cell-mediated cytotoxicity. Ctx increased cAMP levels in NK cells. However, inhibition of IP3 release preceded the rise of cAMP. Moreover, cAMP analogues (8-chlor-cAMP, 8-bromo-cAMP, dibutiryl-cAMP), as well as intracellular cAMP-enhancing agents (PGE1, PGE2, and forskolin) did not mimicked the effects of Ctx on IP3 generation, suggesting that the adenylate cyclase pathway is not responsible for the early effects of Ctx on FcγRIII-mediated signaling. Overall these results demonstrate that signal transduction via FcγRIII is mediated by Ctx-sensitive cellular membrane GTP-binding protein.

Original languageEnglish
Pages (from-to)3550-3556
Number of pages7
JournalJournal of Immunology
Volume146
Issue number10
Publication statusPublished - May 15 1991

ASJC Scopus subject areas

  • Immunology

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    Procopio, A. D. G., Paolini, R., Vecchio, I., Frati, L., & Santoni, A. (1991). GTP-binding proteins transduce signals generated via human FCγ receptor IIIA (CD16). Journal of Immunology, 146(10), 3550-3556.