tailieunhanh - Báo cáo khoa học: Cellular and molecular action of the mitogenic protein-deamidating toxin from Pasteurella multocida

The mitogenic toxin fromPasteurella multocida(PMT) is a member of the dermonecrotic toxin family, which includes toxins fromBordetella, Escheri-chia coliandYersinia. Members of the dermonecrotic toxin family modu-late G-protein targets in host cells through selective deamidation and⁄or transglutamination of a critical active site Gln residue in the G-protein tar-get, which results in the activation of intrinsic GTPase activity. | IFEBS Journal REVIEW ARTICLE Cellular and molecular action of the mitogenic protein-deamidating toxin from Pasteurella multocida Brenda A. Wilson and Mengfei Ho Department of Microbiology and Host-Microbe Systems Theme of the Institute for Genomic Biology University of Illinois at Urbana-Champaign USA Keywords adipogenesis atrophic rhinitis deamidation dermonecrotic toxin G protein membrane translocation mitogenesis osteogenesis receptor-mediated endocytosis transglutamination Correspondence B. A. Wilson Department of Microbiology and Host-Microbe Systems Theme of the Institute for Genomic Biology University of Illinois at Urbana-Champaign Urbana IL 61801 USA Fax 217 244 6697 Tel 217 244 9631 E-mail bawilson@ Received 24 March 2011 revised 20 April 2011 accepted 4 May 2011 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 a subunits of heterotrimeric Gq- Gi-and G12 13-protein families. To date experimental evidence supports a model in which PMT potently stimulates various mitogenic and survival pathways through the activation of Gq and G12 13 signaling ultimately leading to cellular proliferation whilst strongly inhibiting pathways involved in cellular differentiation through the activation of Gi 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 .