PMID- 9469451 OWN - NLM STAT- MEDLINE DCOM- 19980226 LR - 20071115 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 160 IP - 4 DP - 1998 Feb 15 TI - RANTES activation of phospholipase D in Jurkat T cells: requirement of GTP-binding proteins ARF and RhoA. PG - 1894-900 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-1 beta (but not macrophage-inflammatory protein-1 alpha), monocyte-chemotactic protein-1 (MCP-1), MCP-3, MCP-4, and eotaxin. RANTES-induced PLD activation was augmented by GTP gamma S, but not GDP beta S, 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. FAU - Bacon, K B AU - Bacon KB AD - Department of Immunobiology, DNAX Research Institute, Palo Alto, CA 94304, USA. Kbacon@neurocrine.com FAU - Schall, T J AU - Schall TJ FAU - Dairaghi, D J AU - Dairaghi DJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Chemokine CCL5) RN - 0 (Cyclopentanes) RN - 0 (Epoxy Compounds) RN - 0 (Spiro Compounds) RN - 152697-41-1 (diepoxin sigma) RN - 20350-15-6 (Brefeldin A) RN - 37589-80-3 (Guanosine 5'-O-(3-Thiotriphosphate)) RN - EC 2.7.11.13 (Protein Kinase C) RN - EC 3.1.4.4 (Phospholipase D) RN - EC 3.6.1.- (GTP-Binding Proteins) RN - EC 3.6.5.2 (ADP-Ribosylation Factors) RN - EC 3.6.5.2 (rhoA GTP-Binding Protein) SB - IM MH - ADP-Ribosylation Factors MH - Amino Acid Sequence MH - Brefeldin A MH - Chemokine CCL5/antagonists & inhibitors/*pharmacology MH - Cyclopentanes/pharmacology MH - Drug Synergism MH - Enzyme Activation/drug effects MH - Epoxy Compounds/pharmacology MH - GTP-Binding Proteins/*physiology MH - Guanosine 5'-O-(3-Thiotriphosphate)/physiology MH - Humans MH - Jurkat Cells MH - Molecular Sequence Data MH - Phospholipase D/antagonists & inhibitors/*metabolism MH - Protein Binding MH - Protein Kinase C/physiology MH - Spiro Compounds/pharmacology MH - T-Lymphocytes/drug effects/*enzymology MH - rhoA GTP-Binding Protein EDAT- 1998/02/20 00:00 MHDA- 1998/02/20 00:01 CRDT- 1998/02/20 00:00 PHST- 1998/02/20 00:00 [pubmed] PHST- 1998/02/20 00:01 [medline] PHST- 1998/02/20 00:00 [entrez] PST - ppublish SO - J Immunol. 1998 Feb 15;160(4):1894-900.