PMID- 10614772 OWN - NLM STAT- MEDLINE DCOM- 20000113 LR - 20190516 IS - 0741-5400 (Print) IS - 0741-5400 (Linking) VI - 66 IP - 6 DP - 1999 Dec TI - Trp-Lys-Tyr-Met-Val-D-Met is a chemoattractant for human phagocytic cells. PG - 915-22 AB - Trp-Lys-Tyr-Met-Val-D-Met (WKYMVm) is a synthetic peptide that stimulates phosphoinositide (PI) hydrolysis in human leukocytes. The peptide binds to a unique cell surface receptor(s). Recently we had demonstrated that human neutrophils, monocytes, and B lymphocytes express this peptide-specific receptor and that stimulation of human leukocytes with the peptide leads to activation of the oxidative respiratory system and the bactericidal activity of neutrophils or monocytes. In this study we showed that the peptide induces chemotaxis of phagocytic leukocytes and studied the signaling pathway leading to chemotaxis in human monocytes. The peptide-induced monocyte chemotaxis is pertussis toxin (PTX)-sensitive. This fact correlates with the peptide's stimulation of PI hydrolysis and intracellular Ca2+ ([Ca2+]i) release, which is also PTX-sensitive. We demonstrate that the peptide-specific receptor is different from receptor(s) for monocyte chemoattractant protein-1 (MCP-1). We also show that intracellular signaling of WKYMVm leading to monocyte chemotaxis is different from that of MCP-1. The peptide-mediated monocyte chemotaxis is insensitive to protein kinase C (PKC) inhibitor (GF109203X) and butan-1-ol, ruling out PKC and phospholipase D participation in this process. On the other hand, a tyrosine kinase inhibitor (genistein) and RhoA inhibitor (C3 transferase) curtailed the peptide-induced chemotaxis in a concentration-dependent manner, implying the involvement of tyrosine kinase and RhoA, respectively. Treatment of human monocytes with the peptide stimulates tyrosine phosphorylation of several cellular proteins, including p125FAK and Pyk2 and translocation of RhoA from the cytosol to the membrane. We conclude that WKYMVm induces chemotaxis of human phagocytic leukocytes via unique receptors and signaling. FAU - Bae, Y S AU - Bae YS AD - Department of Life Science, Pohang University of Science and Technology, Korea. FAU - Kim, Y AU - Kim Y FAU - Kim, Y AU - Kim Y FAU - Kim, J H AU - Kim JH FAU - Suh, P G AU - Suh PG FAU - Ryu, S H AU - Ryu SH LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Leukoc Biol JT - Journal of leukocyte biology JID - 8405628 RN - 0 (CCR2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Enzyme Inhibitors) RN - 0 (Indoles) RN - 0 (Maleimides) RN - 0 (Monocyte Chemoattractant Proteins) RN - 0 (Oligopeptides) RN - 0 (Receptors, CCR2) RN - 0 (Receptors, Chemokine) RN - 0 (Trp-Lys-Tyr-Met-Val-Met) RN - 0 (Virulence Factors, Bordetella) RN - 8PJ61P6TS3 (1-Butanol) RN - EC 2.4.2.31 (Pertussis Toxin) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 3.1.4.4 (Phospholipase D) RN - EC 3.6.1.- (GTP-Binding Proteins) RN - EC 3.6.5.2 (rhoA GTP-Binding Protein) RN - L79H6N0V6C (bisindolylmaleimide I) SB - IM MH - 1-Butanol/pharmacology MH - B-Lymphocytes/cytology/drug effects/physiology MH - Chemokine CCL2/physiology MH - Chemotaxis, Leukocyte/*drug effects/physiology MH - Enzyme Inhibitors/pharmacology MH - GTP-Binding Proteins/metabolism/physiology MH - Humans MH - Indoles/pharmacology MH - Maleimides/pharmacology MH - Monocyte Chemoattractant Proteins/*pharmacology MH - Monocytes/cytology/*drug effects/enzymology/physiology MH - Neutrophils/cytology/*drug effects/physiology MH - Oligopeptides/*pharmacology MH - Pertussis Toxin MH - Phospholipase D/antagonists & inhibitors/metabolism MH - Protein-Tyrosine Kinases/antagonists & inhibitors/metabolism MH - Receptors, CCR2 MH - Receptors, Chemokine/physiology MH - Virulence Factors, Bordetella/pharmacology MH - rhoA GTP-Binding Protein/physiology EDAT- 1999/12/30 00:00 MHDA- 1999/12/30 00:01 CRDT- 1999/12/30 00:00 PHST- 1999/12/30 00:00 [pubmed] PHST- 1999/12/30 00:01 [medline] PHST- 1999/12/30 00:00 [entrez] AID - 10.1002/jlb.66.6.915 [doi] PST - ppublish SO - J Leukoc Biol. 1999 Dec;66(6):915-22. doi: 10.1002/jlb.66.6.915.