Ras, Rap, and Rac Small GTP-binding Proteins Are Targets for Clostridium sordellii Lethal Toxin Glucosylation

• DOI: 10.1074/jbc.271.17.10217
• Publication Date: 2002-07-26T14:52:05Z
• Authors: Michel R. Popoff; Esteban Chaves-Ol...; Emmanuel Lemichez; Christoph von Eic...; Monica Thelestam; Pierre Chardin; Didier Cussac; Bruno Antonny; Philippe Chavrier; Gilles Flatau; Murielle Giry; Jean de Gunzburg; Patrice Boquet
• Keywords: Clostridium; 0301 basic medicine; Epidermal Growth Factor; Bacterial Toxins; Molecular Sequence Data; 3T3 Cells; Actins; GTP Phosphohydrolases; 3. Good health; Proto-Oncogene Proteins p21(ras); Actin Cytoskeleton; Kinetics; Mice; 03 medical and health sciences; Glucose; GTP-Binding Proteins; Glucosyltransferases; Calcium-Calmodulin-Dependent Protein Kinases; Animals; Humans; Amino Acid Sequence; Guanosine Triphosphate; HeLa Cells

Lethal toxin (LT) from Clostridium sordellii is one of the high molecular mass clostridial cytotoxins. On cultured cells, it causes a rounding cell bodies and disruption actin stress fibers. We demonstrate that LT glucosyltransferase uses UDP-Glc as cofactor to covalently modify 21-kDa proteins both in vitro vivo. glucosylates Ras, Rap, Rac. In threonine at position 35 was identified target amino acid glucosylated by LT. Other related members Ras GTPase superfamily, including RhoA, Cdc42, Rab6, were not modified Incubation serum-starved Swiss 3T3 cells with prevents epidermal growth factor-induced phosphorylation mitogen-activated protein kinases ERK1 ERK2, indicating blocks function also acts inside glucosylation reaction required observe its dramatic effect on morphology. thus powerful tool inhibit