Pasteurella multocida toxin facilitates inositol phosphate formation by bombesin through tyrosine phosphorylation of G alpha q.
The intracellularly acting Pasteurella multocida toxin (PMT) is a potent mitogen that stimulates Gq-dependent formation of inositol trisphosphate. We show that PMT, a nontoxic mutant of PMT (PMTC1165S), and bombesin each stimulate time-dependent phosphorylation of G alpha q at tyrosine 349. Although PMT and PMTC1165S each cause phosphorylation of G alpha q, only the wild-type toxin activates Gq. Pretreatment of cells with wild-type or mutant PMT potentiated the formation of inositol phosphates stimulated by bombesin equally. These data show that PMT potentiates bombesin receptor signaling through tyrosine phosphorylation of Gq and distinguishes between the two proposed models of Gq activation, showing that tyrosine phosphorylation is not linked to receptor uncoupling.
Baldwin
Michael R
MR
Department of Microbiology, Dental Institute, King's College London, Floor 28 Guy's Tower, Guy's Hospital, London, SE1 9RT, United Kingdom.
Pullinger
Gillian D
GD
Lax
Alistair J
AJ
D016475:3T3 Cells; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000494:pharmacology*; D001427:Bacterial Toxins / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D001839:Bombesin / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D019204:GTP-Binding Proteins / Q000378:metabolism; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D016979:Pasteurella multocida / Q000378:metabolism*; D010766:Phosphorylation; D011233:Precipitin Tests; D018004:Receptors, Bombesin / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014443:Tyrosine / Q000737:chemistry / Q000378:metabolism*
D001426:Bacterial Proteins; D001427:Bacterial Toxins; C062258:Pasteurella multocida toxin; D018004:Receptors, Bombesin; D014443:Tyrosine; D019204:GTP-Binding Proteins; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020962:Heterotrimeric GTP-Binding Proteins; D001839:Bombesin