title: Trp-Lys-Tyr-Met-Val-D-Met is a chemoattractant for human phagocytic cells.
abstract: 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.
authors.affiliation: Department of Life Science, Pohang University of Science and Technology, Korea.
authors.forename: Y S
authors.initials: YS
authors.lastname: Bae
authors.forename: Y
authors.initials: Y
authors.lastname: Kim
authors.forename: Y
authors.initials: Y
authors.lastname: Kim
authors.forename: J H
authors.initials: JH
authors.lastname: Kim
authors.forename: P G
authors.initials: PG
authors.lastname: Suh
authors.forename: S H
authors.initials: SH
authors.lastname: Ryu
mesh_terms: D020001:1-Butanol / Q000494:pharmacology; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D018932:Chemokine CCL2 / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D018945:Monocyte Chemoattractant Proteins / Q000494:pharmacology*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology*; D037342:Pertussis Toxin; D010739:Phospholipase D / Q000037:antagonists & inhibitors / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000502:physiology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D020742:rhoA GTP-Binding Protein / Q000502:physiology
chemical_list: C515334:CCR2 protein, human; D018932:Chemokine CCL2; D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D018945:Monocyte Chemoattractant Proteins; D009842:Oligopeptides; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; C113617:Trp-Lys-Tyr-Met-Val-Met; D010566:Virulence Factors, Bordetella; D020001:1-Butanol; D037342:Pertussis Toxin; D011505:Protein-Tyrosine Kinases; D010739:Phospholipase D; D019204:GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein; C070515:bisindolylmaleimide I