title: Cellular and molecular action of the mitogenic protein-deamidating toxin from Pasteurella multocida.
abstract: The mitogenic toxin from Pasteurella multocida (PMT) is a member of the dermonecrotic toxin family, which includes toxins from Bordetella, Escherichia coli and Yersinia. Members of the dermonecrotic toxin family modulate G-protein targets in host cells through selective deamidation and/or transglutamination of a critical active site Gln residue in the G-protein target, which results in the activation of intrinsic GTPase activity. Structural and biochemical data point to the uniqueness of PMT among these toxins in its structure and action. Whereas the other dermonecrotic toxins act on small Rho GTPases, PMT acts on the α subunits of heterotrimeric G(q) -, G(i) - and G(12/13) -protein families. To date, experimental evidence supports a model in which PMT potently stimulates various mitogenic and survival pathways through the activation of G(q) and G(12/13) signaling, ultimately leading to cellular proliferation, whilst strongly inhibiting pathways involved in cellular differentiation through the activation of G(i) signaling. The resulting cellular outcomes account for the global physiological effects observed during infection with toxinogenic P. multocida, and hint at potential long-term sequelae that may result from PMT exposure.
authors.affiliation: Department of Microbiology and Host-Microbe Systems Theme of the Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. bawilson@life.illinois.edu
authors.forename: Brenda A
authors.initials: BA
authors.lastname: Wilson
authors.forename: Mengfei
authors.initials: M
authors.lastname: Ho
mesh_terms: D050156:Adipogenesis; D001427:Bacterial Toxins / Q000378:metabolism*; D049109:Cell Proliferation; D000242:Cyclic AMP / Q000378:metabolism; D003603:Cytotoxins / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism; D008938:Mitosis; D010012:Osteogenesis; D010326:Pasteurella Infections / Q000378:metabolism / Q000382:microbiology; D016979:Pasteurella multocida / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction; D013379:Substrate Specificity; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: D001427:Bacterial Toxins; D003603:Cytotoxins; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D020741:rho GTP-Binding Proteins