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Blood, 15 July 2005, Vol. 106, No. 2, pp. 577-583. Prepublished online as a Blood First Edition Paper on April 7, 2005; DOI 10.1182/blood-2004-10-4100. This Article Full Text (PDF) Supplemental Figure All Versions of this Article: 2004-10-4100v1 106/2/577    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Galandrini, R. Articles by Santoni, A. Search for Related Content PubMed PubMed Citation Articles by Galandrini, R. Articles by Santoni, A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 25, 2004 Accepted March 14, 2005 ARF6: A new player in the FcRIIIA lymphocyte-mediated cytotoxicity Ricciarda Galandrini*, Federica Micucci, Ilaria Tassi, Maria G Cifone, Benedetta Cinque, Mario Piccoli, Luigi Frati, and Angela Santoni Department of Experimental Medicine and Pathology, Istituto Pasteur-Fondazione Cenci-Bolognetti, University 'La Sapienza', Rome, Italy Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy Department of Experimental Medicine and Pathology, Istituto Pasteur-Fondazione Cenci-Bolognetti, University 'La Sapienza', Rome, Italy; Istituto Mediterraneo di Neuroscienze 'Neuromed', Pozzilli, Italy * Corresponding author; email: ricciarda.galandrini{at}uniroma1.it. The activation of phosphoinositide metabolism represents a critical step in the signaling pathways leading to the activation of cytolytic machinery but its regulation is partially understood. We report here that the stimulation of the low affinity receptor for IgG (FcRIIIA, CD16) on primary human natural killer (NK) cells induces a phosphatidylinositol 3-kinase(PI3K)-dependent activation of the small GTPase Arf6. We firstly demonstrate a functional role for Arf6-dependent signals in the activation of the antibody-dependent cellular cytotoxicity (ADCC) attributable to the control of secretion of lytic granule content. We also show that Arf6 couples CD16 to the lipid modifying enzymes phosphatidylinositol4phosphate 5-kinase type I alpha (PI5KI) and phospholipase D (PLD) which are involved in the control of granule secretion; Arf6, but not Rho family small G proteins RhoA and Rac1, is required for receptor-induced PI5KI membrane targeting as well as for PI5KI and PLD activation. Our findings suggest that Arf6 plays a crucial role in the generation of a phosphatidylinositol4,5-bisphosphate (PIP2) plasma membrane pool required for cytolytic granule-mediated target cell killing. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Colonna Below the NK-cell surface: PIP2. Blood, April 15, 2008; 111(8): 3916 - 3916. [Full Text] [PDF] F. Micucci, C. Capuano, E. Marchetti, M. Piccoli, L. Frati, A. Santoni, and R. Galandrini PI5KI-dependent signals are critical regulators of the cytolytic secretory pathway Blood, April 15, 2008; 111(8): 4165 - 4172. [Abstract] [Full Text] [PDF] M. M. Andzelm, X. Chen, K. Krzewski, J. S. Orange, and J. L. Strominger Myosin IIA is required for cytolytic granule exocytosis in human NK cells J. Exp. Med., October 1, 2007; 204(10): 2285 - 2291. [Abstract] [Full Text] [PDF] J. Gomez-Cambronero, M. Di Fulvio, and K. Knapek Understanding phospholipase D (PLD) using leukocytes: PLD involvement in cell adhesion and chemotaxis J. Leukoc. Biol., August 1, 2007; 82(2): 272 - 281. [Abstract] [Full Text] [PDF]

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