Pleiotropic effects of pasteurella multocida toxin are mediated by G q-dependent and -independent mechanisms. Involvement of G q but not G11

Abstract

Pasteurella multocida toxin (PMT) is a highly potent mitogen for a variety of cell types. PMT has been shown to induce various cellular signaling processes, and it has been suggested to function through the heterotrimeric G-proteins Gq/G11. To analyze the role of G q/G11 in the action of PMT, we have studied the effect of the toxin in Gαq/Gα11 double-deficient fibroblasts as well as in fibroblasts lacking only Gαq or Gα11. Interestingly, formation of inositol phosphates in response to PMT was exclusively dependent on Gαq but not on the closely related Gα11. Although Gα q/Gα11 double-deficient and Gα q-deficient cells did not respond with any production of inositol phosphates to PMT, PMT was still able to induce various other cellular effects in these cells, including the activation of Rho, the Rho-dependent formation of actin stress fibers and focal adhesions, as well as the stimulation of c-Jun N-terminal kinase and extracellular signal-regulated kinase. These data show that PMT leads to a variety of cellular effects that are mediated only in part by the heterotrimeric G-protein Gq.