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Pasteurella multocida toxin activates G beta gamma dimers of heterotrimeric G proteins
The mitogenic Pasteurella multocida toxin (PMT) is a major virulence factor of P. multocida, which causes Pasteurellosis in man and animals. The toxin activates the small GTPase RhoA, the MAP kinase ERK and STAT proteins via the stimulation of members of two G protein families, Gq and G12/13. PMT ac...
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Published in: | Cellular signalling 2009-04, Vol.21 (4), p.551-558 |
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Main Authors: | , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Online Access: | Get full text |
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Summary: | The mitogenic Pasteurella multocida toxin (PMT) is a major virulence factor of P. multocida, which causes Pasteurellosis in man and animals. The toxin activates the small GTPase RhoA, the MAP kinase ERK and STAT proteins via the stimulation of members of two G protein families, Gq and G12/13. PMT action also results in an increase in inositol phosphates, which is due to the stimulation of PLC beta via G alpha q. Recent studies indicate that PMT additionally activates G alpha i to inhibit adenylyl cyclase. Here we show that PMT acts not only via G alpha but also through G beta gamma signaling. Activation of G beta gamma by PMT causes stimulation of phosphoinositide 3-kinase (PI3K) gamma and formation of phosphatidylinositol-3,4,5-trisphosphate (PIP3) as indicated by the recruitment of a PIP3-binding pleckstrin homology (PH) domain-containing protein to the plasma membrane. Moreover, it is demonstrated that G beta gamma is necessary for PMT-induced signaling via G alpha . Mutants of G alpha q incapable of binding or releasing G beta gamma are not activated by PMT. Similarly, sequestration of G beta gamma inhibits PMT-induced G alpha -signaling. |
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ISSN: | 0898-6568 |
DOI: | 10.1016/j.cellsig.2008.12.007 |