Pleiotropic effects of Pasteurella multocida toxin are mediated by G(q)-dependent and -independent mechanisms - Involvement of G(q) but not G(11)

Pasteurella multocida toxin (PRTT) is a highly potent mitogen for a variety of cell types. PMT has been shown to induce various cellular signaling pro cesses, and it has been suggested to function through the heterotrimeric G- proteins G(q)/G(11). To analyze the role of G(q)/G(11) in the action of PMT , we have studied the effect of the toxin in G alpha (q)/G alpha (11) doubl e-deficient fibroblasts as web as in fibroblasts lacking only G alpha (q) o r G alpha (11). Interestingly, formation of inositol phosphates in response to PIT was exclusively dependent on Go, but not on the closely related G a lpha (11). Although G alpha (q)/G alpha (11) double-deficient and G alpha ( q)-deficient cells did not respond with any production of inositol phosphat es to PMT, PMT was still able to induce various other cellular effects in t hese cells, including the activation of Rho, the Rho-dependent formation of actin stress fibers and focal adhesions, as well as the stimulation of c-J un 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 G(q).