title: Escherichia coli LT enterotoxin subunit A demonstrates partial toxicity independent of the nicking around Arg192.
abstract: A study was conducted into whether or not nicking of the A subunit of Escherichia coli LT enterotoxin at position Arg192 or its neighbouring amino acids Arg192 to The195 is required for its toxicity. The toxic activity of mutants created by substitution or deletion at this position, which lacked ADP-ribosyltransferase activity in vitro, was not completely obliterated and cyclic AMP was partially induced in the target cells, showing that they still displayed enzymic activity in vivo. Moreover, although the A subunit possesses three potential sites for cleavage by furin, furin was not involved in the partial toxicity and cyclic AMP induction observed. These data suggest that target cells have a nick mechanism that operates at sites other than those around Arg192 or those recognized by furin, which generates an active fragment by processing the A subunit after toxin binding to the cell membrane.
authors.affiliation: Department of Microbiology, Fujita Health University, School of Medicine, Toyoake, Aichi, 470-11, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Tsuji
authors.affiliation: Department of Microbiology, Fujita Health University, School of Medicine, Toyoake, Aichi, 470-11, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Kato
authors.affiliation: Department of Microbiology, Fujita Health University, School of Medicine, Toyoake, Aichi, 470-11, Japan.
authors.forename: Hidetsugu
authors.initials: H
authors.lastname: Kawase
authors.affiliation: Department of Microbiology, Fujita Health University, School of Medicine, Toyoake, Aichi, 470-11, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Imamura
authors.affiliation: Department of Microbiology, Fujita Health University, School of Medicine, Toyoake, Aichi, 470-11, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kamiya
authors.affiliation: Department of Bacteriology, Institute of Tropical Medicine, Nagasaki University, 1-12-4, Sakamoto, Nagasaki 852, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Ichinose
authors.affiliation: Department of Microbiology, Fujita Health University, School of Medicine, Toyoake, Aichi, 470-11, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Miyama
mesh_terms: D036002:ADP Ribose Transferases / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000235:genetics / Q000378:metabolism*; D001427:Bacterial Toxins / Q000737:chemistry / Q000235:genetics* / Q000633:toxicity; D001665:Binding Sites; D016466:CHO Cells / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D003850:Deoxyribonuclease I / Q000378:metabolism; D004768:Enterotoxins / Q000737:chemistry / Q000235:genetics* / Q000633:toxicity; D004926:Escherichia coli / Q000235:genetics; D029968:Escherichia coli Proteins; D045683:Furin; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009152:Mutagenicity Tests; D013381:Subtilisins / Q000378:metabolism
chemical_list: D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D001120:Arginine; C027538:heat-labile enterotoxin, E coli; D000242:Cyclic AMP; D036002:ADP Ribose Transferases; D003850:Deoxyribonuclease I; D013381:Subtilisins; D045683:Furin