ADP-ribosylation of transducin by pertussis toxin blocks the light-stimulated hydrolysis of GTP and cGMP in retinal photoreceptors.

Dop, Cornelis Van; Yamanaka, Gregory; Steinberg, F; Sekura, Ronald D.; Manclark, C R; Stryer, Lubert; Bourne, Henry R.

doi:10.1016/s0021-9258(17)43615-5

Cited by 323 publications

(23 citation statements)

References 31 publications

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“…For example, Manning and Gilman (1983) have found that the photoreceptor G-protein has structural similarities with both inhibitory and stimulatory guanine nucleotide binding proteins, and Abood et al . (1982) andVanDop et al . (1984) have found that bovine photoreceptor G-protein can be ADP-ribosylated at different sites by two toxins, cholera toxin and pertussis toxin, with different effects on its function .…”

Section: Discussionmentioning

confidence: 98%

A monoclonal antibody to guanine nucleotide binding protein inhibits the light-activated cyclic GMP pathway in frog rod outer segments.

Hamm¹,

Bownds²

1984

The Journal of General Physiology

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A monoclonal antibody that blocks the light-activated cyclic GMP (cGMP) pathway in frog photoreceptor outer segments (ROS) has been obtained . The antibody (4A) inhibits guanine nucleotide binding to G-protein, the intermediate that links rhodopsin excitation to cGMP phosphodiesterase (PDE), inhibiting light-induced PDE activity as a consequence . Antibody inhibition of the light-activated cGMP pathway is complete at a stoichiometry of approximately one antibody per G-protein in the mixture, which indicates high specificity of the inhibition . Inhibition is more pronounced than that caused by PDE inhibitors such as isobutylmethylxanthine (IBMX) or Ro 20-1724 . Antibody 4A has the further effect of inhibiting the phosphorylation of two low molecular weight proteins, components I and 11, whose phosphorylation normally can be stimulated by raising cGMP levels . The inhibition is not overridden by adding cGMP, which suggests that the G-protein influences these phosphorylations by a pathway distinct from its action on cGMP concentration . Antibody 4A may prove useful as a probe of the relevance of the cGMP pathway to visual transduction in living photoreceptors . Six other monoclonal antibodies to Gprotein, as well as six monoclonal antibodies to rhodopsin and one to PDE, do not block light-activated guanine nucleotide binding, PDE activity, or ROS protein phosphorylations .

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Section: Discussionmentioning

confidence: 98%

A monoclonal antibody to guanine nucleotide binding protein inhibits the light-activated cyclic GMP pathway in frog rod outer segments.

Hamm¹,

Bownds²

1984

The Journal of General Physiology

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“…For the purified G protein, Gs, and the purified dihydropyridine receptor Ca z+ channel, a direct effect has been shown (Hamilton et al, 1990). Our hypothesis is based on the findings that: (a) basal noise currents are identical to agonist-activated currents; (b) candidate endogenous agonists have been excluded; (c) specific G~-3c~ antibodies block agonist-independent activation; (d) PTX also blocks activation and is reported to have no effects on GTP-ase activity, binding of GTP, or release of GDP from Gi~ (Van Dop et al, 1984;Gilman, 1987;Sullivan et al, 1987;Sunyer et al, 1989); and (e) ras p21 in combination with the GTPase activating protein (GAP) blocked basal atrial K+[ACh] currents (Yatani et al, 1990b). However, ras p21-GAP did not interact with either Gi-3 or the K+[ACh] channel, so that the block was upstream of the G protein between it and the receptor (Yatani et al, 1990b).…”

Section: Discussionmentioning

confidence: 99%

“…1, 4, and 5). Thus, coupling of receptor to G protein may be essential for agonist-free K+[ACh] currents under the condition that ADP ribosylation by FTX had only an uncoupling effect (Van Dop et al, 1984;Gilman, 1987;Sullivan et al, 1987;Sunyer et al, 1989).…”

Section: Uncoupling or Inactivating Empty Receptorsmentioning

confidence: 99%

The nature and origin of spontaneous noise in G protein-gated ion channels.

Okabe

Yatani

Brown

1991

The Journal of General Physiology

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A B S TRACT Arrival of agonist is generally thought to initiate the signal transduction process in G protein-receptor coupled systems. However, the muscarinic atrial K + (K+[ACh]) channel opens spontaneously in the absence of applied agonist, giving a noisy appearance to the current records. We investigated the nature and origin of the noise by measuring single channel currents in cell-attached or excised, insideout membrane patches. Guanosine triphosphate (GTP) produced identical single channel currents in a concentration-and Mg~+-dependent manner in the presence or absence of carbachol, but the requirements for GTP were greater in the absence of agonist. Hence the agonist-independent currents appeared to be produced by an endogenous G protein, Gk. This prediction was confirmed when an afffinity-purified, sequence-specific G~-3a antibody or pertussis toxin (PTX) blocked the agonistindependent currents. Candidate endogenous agonists were ruled out by the lack of effect of their corresponding antagonists. Thus agonist-independent currents had the same nature as agonist-dependent K+[ACh] currents and seemed to originate in the same way. We have developed a hypothesis in which agonist-free, empty receptors prime Gk with GTP and G k activates atrial K ÷ [ACh] channels producing basal currents or noise. Agonist-independent activation by G proteins of effectors including ion channels appears to be a common occurrence.

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“…• " 32 performed in 0.I M sucrose containing 10 ~M c~-[ P]NAD, 2.5 mM MgCl2, 1 mM ATP, 10 mM thymidine, 1 mM dithiothreitol, and 5 mM Tris-HCl (pH 7.2), as previously described (19,36). The reaction was terminated by the addition of 5 vol of Laemmli sample buffer (37).…”

Section: Methodsmentioning

confidence: 99%

Pertussis toxin inhibition of chemotactic factor-induced calcium mobilization and function in human polymorphonuclear leukocytes.

Goldman¹,

Chang²,

Gifford³

et al. 1985

The Journal of Experimental Medicine

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177

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Chemotactic factors stimulate a rapid increase in the cytosolic concentration of intracellular calcium ions ([Ca2+]in) in human polymorphonuclear leukocytes (PMNL), which may be an event that is critical to the expression of chemotaxis and other PMNL functions. Treatment of PMNL with pertussis toxin catalyzes ADP-ribosylation of a protein similar or identical to the inhibiting regulatory protein of adenylate cyclase, Gi, and suppresses the increase in [Ca2+]in elicited by leukotriene B4(LTB4) and formyl-methionyl-leucyl-phenylalanine. Chemotactic migration and lysosomal enzyme release elicited by chemotactic factors were inhibited by pertussis toxin with a concentration-dependence similar to that for inhibition of the increase in [Ca2+]in, without an effect on lysosomal enzyme release induced by the ionophore A23187 and phorbol myristate acetate. Activated pertussis toxin catalyzed the [32P]ADP-ribosylation of a 41 kD protein in homogenates of PMNL. The extent of [32P]ADP-ribosylation of this protein was reduced 59% by pretreatment of intact PMNL with pertussis toxin. Pertussis toxin selectively decreased the number of high-affinity receptors for LTB4 on PMNL by 60% without altering the number or binding properties of the low-affinity subset of receptors. Pertussis toxin modification of a membrane protein of PMNL analogous to Gi thus simultaneously alters chemotactic receptors and attenuates the changes in cytosolic calcium concentration and PMNL function caused by chemotactic factors.

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ADP-ribosylation of transducin by pertussis toxin blocks the light-stimulated hydrolysis of GTP and cGMP in retinal photoreceptors.

Cited by 323 publications

References 31 publications

A monoclonal antibody to guanine nucleotide binding protein inhibits the light-activated cyclic GMP pathway in frog rod outer segments.

A monoclonal antibody to guanine nucleotide binding protein inhibits the light-activated cyclic GMP pathway in frog rod outer segments.

The nature and origin of spontaneous noise in G protein-gated ion channels.

Pertussis toxin inhibition of chemotactic factor-induced calcium mobilization and function in human polymorphonuclear leukocytes.

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