Signal transduction pertussis toxin

Excitation of smooth muscle via alpha-1 receptors (eg, in the utems, vascular smooth muscle) is accompanied by an increase in intraceUular-free calcium, possibly by stimulation of phosphoUpase C which accelerates the breakdown of polyphosphoinositides to form the second messengers inositol triphosphate (IP3) and diacylglycerol (DAG). IP3 releases intracellular calcium, and DAG, by activation of protein kinase C, may also contribute to signal transduction. In addition, it is also thought that alpha-1 adrenergic receptors may be coupled to another second messenger, a pertussis toxin-sensitive G-protein that mediates the translocation of extracellular calcium. 

Fig. 12. Tentative model of the signal transduction chain that links the perception of pectic fragments to defense responses in carrot cells. Abbreviations apy, heterotrimeric G protein CaM, calmodulin 4CL, 4-coumarate-CoA ligase CTX, cholera toxin FC, fusicoccine GDP-P-S and GTP-y-S, guanosine 5 -0-(2-thiodiphosphate) and guanosine 5 -0-(3-thiotriphosphate) IP3, 1,4,5-inositol trisphosphate PAL, phenylalanine ammonia-lyase PLC, phospholipase C PR, pathogenesis related PTX, pertussis toxin Rc, receptor SP, staurosporine. Activation and inhibition are symbolized by + and -respectively.

GM-CSF and IL-3 have been shown to compete for receptors in some types of cells (e.g. eosinophils and KG-1 cells), indicating some structural homology between GM-CSF and IL-3 receptors, perhaps because they share certain subunits or adapter proteins. GM-CSF occupancy results in phosphorylation of certain proteins, and because the receptor possesses no inherent kinase activity, receptor occupancy must be linked to kinase activity via the generation of second messenger molecules. Pretreatment of cells with pertussis toxin abolishes the effects of GM-CSF, indicating the involvement of G-proteins in signal transduction. Priming of neutrophil functions with GM-CSF involves the activation of phospholipases A2 and D. 

Presynaptic H3 receptors also are uniform in their signal transduction. They couple to Gi/o proteins and decrease the depolarization-induced release of neurotransmitters by inhibiting multiple calcium channels (e.g., Arrang et al. 1985 Schlicker et al. 1994 Endou et al. 1994 Brown and Haas 1999 see Stark et al. 2004). For comparison, the signal transduction of soma-dendritic H3 autoreceptors in histamin-ergic neurons also involves a pertussis toxin-sensitive G-protein with subsequent inhibition of N- and P-type Ca2+ channels (Takeshita et al. 1998). The few exceptions to this signal transduction pathway are discussed in the corresponding subsections below (see Sections 3.1, 3.3, and 3.9). 

The classical view of GPCR signal transduction involves activation of trimeric G-proteins, and in the case of chemokine receptors, Gai is key, as indicated by their sensitivity to pertussis toxin. However, evolving theories of dimerization-induced signal transduction add an intermediate... 

Although pertussis toxin is a popular tool in signal transduction research, it acts on several G proteins other than G as well, so that the implication of cAMP by toxin inhibition is... 

Whereas cholera is a result of a G protein trapped in the active conformation, causing the signal-transduction pathway to be perpetually stimulated, pertussis, or whooping cough, is a result of the opposite situation. Pertussis toxin also adds an ADP-ribose moiety,— in this case, to a G j protein, a G protein that inhibits adenyl cyclase, closes Ca + channels, and... 

Ui M (1990) Pertussis toxin as a valuable probe for G-protein involvement in signal transduction. In ADP-ribosylating toxins and G proteins. Insights into signal transduction (Moss J, Vaughan M, eds) pp 45-77. 

However, other cells may respond differently to the toxin. In particular, platelets are able to resist the entry of pertussis toxin, either because they lack surface binding sites for the toxin B oligomer or because they are unable to internalize the bound toxin (Brass et al., 1990). PT-sensitive G proteins expressed in insect Sf9 cells (ovary cells from the insect Spodoptera frugiperda Sf9 cells are employed as an overexpression system for G proteins and other signal transduction components by infection with recombinant baculovirus) are also not modified by the toxin (Mulheron et al., 1994). 

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