Pasteurella multocida toxin facilitates inositol phosphate formation by bombesin through tyrosine phosphorylation of G alpha(q)

TY - JOUR

T1 - Pasteurella multocida toxin facilitates inositol phosphate formation by bombesin through tyrosine phosphorylation of G alpha(q)

AU - Baldwin, M R

AU - Pullinger, G D

AU - Lax, A J

PY - 2003/8/29

Y1 - 2003/8/29

N2 - The intracellularly acting Pasteurella multocida toxin (PMT) is a potent mitogen that stimulates G(q)-dependent formation of inositol trisphosphate. We show that PMT, a nontoxic mutant of PMT (PMTC1165S), and bombesin each stimulate time-dependent phosphorylation of Galpha(q) at tyrosine 349. Although PMT and PMTC1165S each cause phosphorylation of Galpha(q), only the wild-type toxin activates G(q). 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 G(q) and distinguishes between the two proposed models of G(q) activation, showing that tyrosine phosphorylation is not linked to receptor uncoupling.

AB - The intracellularly acting Pasteurella multocida toxin (PMT) is a potent mitogen that stimulates G(q)-dependent formation of inositol trisphosphate. We show that PMT, a nontoxic mutant of PMT (PMTC1165S), and bombesin each stimulate time-dependent phosphorylation of Galpha(q) at tyrosine 349. Although PMT and PMTC1165S each cause phosphorylation of Galpha(q), only the wild-type toxin activates G(q). 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 G(q) and distinguishes between the two proposed models of G(q) activation, showing that tyrosine phosphorylation is not linked to receptor uncoupling.

UR - http://www.scopus.com/inward/record.url?scp=0042357452&partnerID=8YFLogxK

U2 - 10.1074/jbc.M303524200

DO - 10.1074/jbc.M303524200

M3 - Article

SN - 1083-351X

VL - 278

SP - 32719

EP - 32725

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

IS - 35

ER -