RT Journal Article
SR Electronic
T1 RANTES Activation of Phospholipase D in Jurkat T Cells: Requirement of GTP-Binding Proteins ARF and RhoA
JF The Journal of Immunology
JO J. Immunol.
FD American Association of Immunologists
SP 1894
OP 1900
VO 160
IS 4
A1 Bacon, Kevin B.
A1 Schall, Thomas J.
A1 Dairaghi, Daniel J.
YR 1998
UL http://www.jimmunol.org/content/160/4/1894.abstract
AB The chemokine RANTES is a potent agonist of T cell activation. In an investigation of signal-transduction events activated by this chemokine, we have shown that RANTES stimulates dose-dependent phospholipase D (PLD) activity in Jurkat cells. Equilibrium-binding analyses using 125I-labeled RANTES indicated the presence of a receptor for RANTES on these cells, which has a Kd of 0.1 nM, is expressed at approximately 600 sites per cell, and a binding specificity that was not comparable with that of any of the known chemokine receptors, since 125I-labeled RANTES was displaced by macrophage-inflammatory protein-1β (but not macrophage-inflammatory protein-1α), monocyte-chemotactic protein-1 (MCP-1), MCP-3, MCP-4, and eotaxin. RANTES-induced PLD activation was augmented by GTPγS, but not GDPβS, and inhibited by the protein kinase C inhibitor bisindolylmaleimide, as well as the fungal metabolite brefeldin A, and C3 exoenzyme (Clostridium botulinum), implicating the activation of RhoA. RANTES also induced GTP-GDP exchange of immunoprecipitated RhoA. RANTES-stimulated PLD activity was dependent on an ADP-ribosylation factor(s), as assessed by inhibition studies using a synthetic inhibitory peptide of the N-terminal 16 amino acids of ADP-ribosylation factor 1. These studies indicate the potential existence of a novel receptor-mediated mechanism for activation of T cells by the chemokine RANTES.