Pharmacology of pertussis toxin B-oligomer.
Pertussis toxin (PTX) is a heterohexameric protein, which is divided into subunits A and B. The A-subunit (protomer) possesses adenine diphosphate (ADP) ribosyltransferase activity, and the B-oligomer confers cell surface binding specificity on the toxin. By virtue of the ADP-ribosylation activity in the A-subunit, PTX has become a very useful pharmacological tool for the identification of inhibitory guanine nucleotide binding (Gi) proteins in the plasma membrane. However, the pharmacological properties of the PTX B-oligomer are largely unknown. In the course of identifying its binding site(s), PTX B-oligomer was recently found to elicit direct cellular responses in a variety of cell types. Several cell surface receptors with oligosaccharide side chains have been shown to be specifically bound by PTX B-oligomer. Moreover, occupation of these putative receptors by the B-oligomer alone can trigger phospholipase C and tyrosine kinase dependent signal transduction events. The impact of these B-oligomer-mediated rapid signaling responses on the subsequent ADP-ribosylation of Gi protein by the A-subunit remains to be determined. These recent findings caution investigators not to attribute inhibitory effects of PTX solely to ADP-ribosylation of Gi protein without first examining the cellular responses using PTX B-oligomer.
Wong
W S
WS
Department of Pharmacology, Faculty of Medicine, National University of Singapore, Republic of Singapore.
Rosoff
P M
PM
D006801:Humans; D009844:Oligosaccharides / Q000737:chemistry / Q000378:metabolism*; D037342:Pertussis Toxin; D011485:Protein Binding; D011493:Protein Kinase C / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D010738:Type C Phospholipases / Q000502:physiology; D010566:Virulence Factors, Bordetella / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D014917:Whooping Cough / Q000517:prevention & control
D009844:Oligosaccharides; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin; D011493:Protein Kinase C; D010738:Type C Phospholipases