Pleiotropic role of Rac in mast cell activation revealed by a cell permeable Bordetella dermonecrotic fusion toxin.
To activate the GTPase Rac in rat basophilic leukemia (RBL) cells and mouse bone marrow-derived mast cells (BMMC) a TAT fusion toxin of Bordetella dermonecrotic toxin (DNT-TAT) was constructed. The fusion toxin activated Rac1 and RhoA in vitro but only Rac in RBL cells and BMMC. DNT-TAT caused an increase in inositol phosphate formation, calcium mobilization, ERK activation and degranulation of mast cells. All these effects were inhibited by the Rho GTPase-inactivating Clostridium difficile toxin B and Clostridium sordellii lethal toxin. Also the calcium ionophore A23187 caused mast cell activation, including ERK phosphorylation, by processes involving an activation of Rac. The data indicate pleiotropic functions of Rac in mast cell activation.
Stratmann
Heidi
H
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Albert-Ludwigs-Universität Freiburg, Germany.
Schwan
Carsten
C
Orth
Joachim H C
JH
Schmidt
Gudula
G
Aktories
Klaus
K
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015550:Cell Degranulation; D002460:Cell Line; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D051379:Mice; D010455:Peptides / Q000235:genetics; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D011503:Transglutaminases / Q000235:genetics / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000235:genetics / Q000494:pharmacology*; D020830:rac1 GTP-Binding Protein / Q000187:drug effects / Q000502:physiology*; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D010455:Peptides; D011993:Recombinant Fusion Proteins; D010566:Virulence Factors, Bordetella; C060969:dermonecrotic toxin, Bordetella; D011503:Transglutaminases; D048049:Extracellular Signal-Regulated MAP Kinases; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins; D002118:Calcium