title: Essential role of protein kinase C zeta in transducing a motility signal induced by superoxide and a chemotactic peptide, fMLP.
abstract: Under various pathological conditions, including infection, malignancy, and autoimmune diseases, tissues are incessantly exposed to reactive oxygen species produced by infiltrating inflammatory cells. We show augmentation of motility associated with morphological changes of human squamous carcinoma SASH1 cells, human peripheral monocytes (hPMs), and murine macrophage-like cell line J774.1 by superoxide stimulation. We also disclose that motility of hPMs and J774.1 induced by a chemotactic peptide (N-formyl-methionyl-leucyl-phenylalanine [fMLP]) was inhibited by superoxide dismutase or N-acetylcystein, indicating stimulation of motility by superoxide generated by fMLP stimulation. In these cells, protein kinase C (PKC) zeta was activated to phosphorylate RhoGDI-1, which liberated RhoGTPases, leading to their activation. These events were inhibited by dominant-negative PKCzeta in SASH1 cells, myristoylated PKCzeta peptides in hPMs and J774.1, or a specific inhibitor of RhoGTPase in SASH1, hPMs, and J774.1. These results suggest a new approach for manipulation of inflammation as well as tumor cell invasion by targeting this novel signaling pathway.
authors: Fourth Department of Internal Medicine, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo 060-8543, Japan.
authors: Kageaki
authors: K
authors: Kuribayashi
authors: Kiminori
authors: K
authors: Nakamura
authors: Maki
authors: M
authors: Tanaka
authors: Tsutomu
authors: T
authors: Sato
authors: Junji
authors: J
authors: Kato
authors: Katsunori
authors: K
authors: Sasaki
authors: Rishu
authors: R
authors: Takimoto
authors: Katsuhisa
authors: K
authors: Kogawa
authors: Takeshi
authors: T
authors: Terui
authors: Tetsuji
authors: T
authors: Takayama
authors: Takayuki
authors: T
authors: Onuma
authors: Takuya
authors: T
authors: Matsunaga
authors: Yoshiro
authors: Y
authors: Niitsu
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D051379:Mice; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009361:Neoplasm Invasiveness; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013482:Superoxide Dismutase / Q000378:metabolism / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism / Q000494:pharmacology*; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D062948:rho Guanine Nucleotide Dissociation Inhibitor alpha; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors; D000099221:Protein Kinase C zeta
chemical_list: D000111:Acetylcysteine; D004791:Enzyme Inhibitors; D020730:Guanine Nucleotide Dissociation Inhibitors; D009240:N-Formylmethionine Leucyl-Phenylalanine; D011493:Protein Kinase C; D013482:Superoxide Dismutase; D013481:Superoxides; D020741:rho GTP-Binding Proteins; D062948:rho Guanine Nucleotide Dissociation Inhibitor alpha; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors; D000099221:Protein Kinase C zeta; C569638:ARHGDIA protein, human; C042932:formylmethionyl-leucyl-phenylalanine methyl ester