The major virulence factor of Pasteurella multocida responsible for atrophic rhinitis, pneumonia-like respiratory disease, and dermonecrosis is a monomeric 1285 amino acid protein toxin (PMT) produced primarily by capsular type D, some capsular type A, and a few non-typable strains. This chapter reviews what is currently known about the structure and molecular action of PMT, its role in pathogenesis, and its interaction with and effects on mammalian cells. Examples are also provided of the use of PMT as a powerful tool to study mitogenic, Gq-protein-, and Rho-protein-dependent signaling mechanisms. The understanding of PMT structure and activity is at a much earlier stage, and a number of outstanding questions remain about its functional organization, additional intracellular targets, and biochemical activity. Yet, because of its unique action on Gq, PMT is already being used as a potent research tool in deciphering cellular signal transduction pathways involving Gq-proteins. PMT facilitation of Gqα-protein coupling to PLCβ1 causes the same cellular responses elicited by Gq-protein-coupled receptors. Down-regulation of Gq- PLC signaling upon prolonged PMT treatment alsoallows for distinguishing between PTx-sensitive and PTx-insensitive signaling pathways that involve Gq.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)