Comunicación celular. Transducción de señales acopladas a proteínas G heterotriméricas

<span>Most of the chemical messengers are hydrophilic molecules that exert their biological effect through transmembrane receptors which couple to heterotrimeric guanine nucleotide binding proteins (Gproteins). These G-proteins are signal transductors and they also represent the central part of a molecular machine which is able to receive, integrate and process information carried out by extracellular signals. Several different mechanisms for signal transduction are known. This paper focuses the molecular mechanisms of signal transduction via heterotrimeric G proteins.</span>

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Halothane Attenuates Calcium Sensitization in Airway Smooth Muscle by Inhibiting G-proteins

Anesthesiology ◽

10.1097/00000542-199812000-00034 ◽

1998 ◽

Vol 89 (6) ◽

pp. 1543-1552 ◽

Cited By ~ 29

Author(s):

Tetsuya Kai ◽

Keith A. Jones ◽

David O. Warner

Keyword(s):

Smooth Muscle ◽

G Proteins ◽

Airway Smooth Muscle ◽

Tracheal Smooth Muscle ◽

Heterotrimeric G Proteins ◽

Calcium Sensitization ◽

Smooth Muscle Preparation ◽

Guanine Nucleotide Binding ◽

Nucleotide Binding Proteins ◽

Guanine Nucleotide Binding Proteins

Background Halothane directly relaxes airway smooth muscle partly by decreasing the Ca2+ sensitivity. In smooth muscle, receptor stimulation is thought to increase Ca2+ sensitivity via a cascade of heterotrimeric and small monomeric guanine nucleotide-binding proteins (G-proteins). Whether this model is applicable in the airway and where halothane acts in this pathway were investigated. Methods A beta-escin-permeabilized canine tracheal smooth muscle preparation was used. Exoenzyme C3 of Clostridium botulinum, which inactivates Rho monomeric G-proteins, was used to evaluate the involvement of this protein in the Ca2+ sensitization pathway. The effects of halothane on different stimulants acting at different levels of signal transduction were compared: acetylcholine on the muscarinic receptor, aluminum fluoride (AIF4-) on heterotrimeric G-proteins, and guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) on all G-proteins. Results Exoenzyme C3 equally attenuated acetylcholine- and AIF4--induced Ca2+ sensitization, suggesting that these pathways are both mediated by Rho. Halothane applied before stimulation equally attenuated acetylcholine- and AIF4--induced Ca2+ sensitization. However, when added after Ca2+ sensitization was established, the effect of halothane was greater during Ca2+ sensitization induced by acetylcholine compared with AIF4-, which, along with the previous result, suggests that halothane may interfere with dissociation of heterotrimeric G-proteins. Halothane applied during GTPgammaS-induced Ca2+ sensitization had no significant effect on force, suggesting that halothane has no effect downstream from monomeric G-proteins. Conclusion Halothane inhibits increases in Ca2+ sensitivity of canine tracheal smooth muscle primarily by interfering with the activation of heterotrimeric G-proteins, probably by inhibiting their dissociation.

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UNCOUPLING OF RECEPTOR-MEDIATED CELLULAR RESPONSES BY IONIC LITHIUM

Journal of Endocrinology ◽

10.1677/joe.0.123r005 ◽

1989 ◽

Vol 123 (2) ◽

pp. R5-R7 ◽

Cited By ~ 5

Author(s):

M. Zaidi ◽

A. Patchell ◽

H.K. Datta ◽

I. MacIntyre

Keyword(s):

Signal Transduction ◽

G Proteins ◽

Cellular Responses ◽

Receptor Interaction ◽

Guanine Nucleotide ◽

Protein Receptor ◽

Guanine Nucleotide Binding ◽

Cortical Membranes ◽

Nucleotide Binding Proteins ◽

Guanine Nucleotide Binding Proteins

ABSTRACT The propensity of ionic lithium to interfere with the coupling of receptors to guanine nucleotide binding proteins (G-proteins) has only recently been investigated using rat cortical membranes. In the present study we have used intact isolated osteoclasts to investigate lithium-induced uncoupling of the receptor-mediated actions of calcitonin. All actions of calcitonin on the osteoclast were abolished by ionic lithium. We believe that the cation prevents signal transduction by inhibiting G protein-receptor interaction, the first step in intracellular signalling.

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G Proteins Large and Small Guanine Nucleotide Binding Proteins

Principles of Molecular Regulation ◽

10.1007/978-1-59259-032-2_2 ◽

2000 ◽

pp. 27-39

Author(s):

Thomas M. Wilkie ◽

Michael A. White

Keyword(s):

G Proteins ◽

Binding Proteins ◽

Nucleotide Binding ◽

Guanine Nucleotide ◽

Guanine Nucleotide Binding ◽

Nucleotide Binding Proteins ◽

Guanine Nucleotide Binding Proteins

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Control of Exocytosis in Single Cells

Physiology ◽

10.1152/physiologyonline.1989.4.2.53 ◽

1989 ◽

Vol 4 (2) ◽

pp. 53-56 ◽

Cited By ~ 1

Author(s):

Y Maruyama

Keyword(s):

Membrane Fusion ◽

G Proteins ◽

Secretory Granule ◽

Single Cells ◽

Guanine Nucleotide ◽

Signal Transducers ◽

Granule Membrane ◽

Guanine Nucleotide Binding ◽

Nucleotide Binding Proteins ◽

Guanine Nucleotide Binding Proteins

Exocytosis can be quantified by measuring changes in membrane capacitance in single internally perfused cells. Exocytosis is controlled by guanine nucleotide-binding proteins (G proteins) acting as key signal transducers. Different G proteins mediate receptor signaling and secretory granule-membrane fusion.

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Alterations of guanine nucleotide -binding proteins (G proteins) in post-mortem human brain and in platelets of alcoholics.

The Japanese Journal of Pharmacology ◽

10.1016/s0021-5198(19)49965-4 ◽

1994 ◽

Vol 64 ◽

pp. 75

Author(s):

Toshikazu Saito ◽

Hiroki Ozawa ◽

Shinichi Hatta

Keyword(s):

Human Brain ◽

G Proteins ◽

Binding Proteins ◽

Nucleotide Binding ◽

Guanine Nucleotide ◽

Post Mortem ◽

Guanine Nucleotide Binding ◽

Nucleotide Binding Proteins ◽

Guanine Nucleotide Binding Proteins

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Plant hormone perception and action: a role for G–protein signal transduction?

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.1998.0297 ◽

1998 ◽

Vol 353 (1374) ◽

pp. 1425-1430 ◽

Cited By ~ 13

Author(s):

Richard Hooley

Keyword(s):

Signal Transduction ◽

G Protein ◽

G Proteins ◽

Plant Hormone ◽

Higher Plants ◽

Signalling Pathways ◽

Heterotrimeric G Proteins ◽

Extracellular Signals ◽

G Protein Signalling ◽

Auxin Signalling

Plants perceive and respond to a profusion of environmental and endogenous signals that influence their growth and development. The G–protein signalling pathway is a mechanism for transducing extracellular signals that is highly conserved in a range of eukaryotes and prokaryotes. Evidence for the existence of G–protein signalling pathways in higher plants is reviewed, and their potential involvement in plant hormone signal transduction evaluated. A range of biochemical and molecular studies have identified potential components of G–protein signalling in plants, most notably a homologue of the G–protein coupled receptor superfamily ( GCR1 ) and the G α and G β subunits of heterotrimeric G–proteins. G–protein agonists and antagonists are known to influence a variety of signalling events in plants and have been used to implicate heterotrimeric G–proteins in gibberellin and possibly auxin signalling. Antisense suppression of GCR1 in Arabidopsis leads to a phenotype which supports a role for this receptor in cytokinin signalling. These observations suggest that higher plants have at least some of the components of G–protein signalling pathways and that these might be involved in the action of certain plant hormones.

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Is Receptor Cross-Regulation in Human Heart Caused by Alterations in Cardiac Guanine Nucleotide-Binding Proteins?

Clinical Science ◽

10.1042/cs0850393 ◽

1993 ◽

Vol 85 (4) ◽

pp. 393-399 ◽

Cited By ~ 4

Author(s):

A. Ferro ◽

C. Plumpton ◽

M. J. Brown

Keyword(s):

G Protein ◽

G Proteins ◽

Atrial Appendage ◽

Right Atrial ◽

Α Subunit ◽

Guanine Nucleotide Binding ◽

Quantitative Changes ◽

Right Atrial Appendage ◽

Nucleotide Binding Proteins ◽

Guanine Nucleotide Binding Proteins

1. Guanine nucleotide-binding proteins (G-proteins) play a central role in signal transduction between a wide variety of cell-surface receptors and intracellular second messenger systems. Recently, we and others have demonstrated that cross-regulation can occur between a variety of G-protein-linked receptors in human heart. Chronic β1-adrenoceptor blockade gives rise to sensitization of β2-adrenoceptor and of 5HT4-receptor responses, both of which are mediated via stimulation of adenylate cyclase through stimulatory G-proteins (Gs), and also gives rise to desensit-ization of muscarinic M2-receptor responses, which inhibit adenylate cyclase through inhibitory G-proteins (Gi). 2. In order to investigate whether these effects are due to quantitative changes in cardiac G-protein isoforms, we measured their abundance in right atrial appendage from patients taking or not taking β1-adrenoceptor antagonists, by immunoblotting. 3. Samples of right atrial appendage homogenate were subjected to SDS/PAGE, and proteins were electroblotted on to nitrocellulose membranes. These were then probed with specific anti-G protein anti-sera, and binding was revealed by means of a secondary antibody labelled with alkaline phosphatase and using a chromogenic substrate. The resulting bands were quantified by laser densitometry. 4. No quantitative differences were detected, between these two groups of patients, in the amounts of α-subunit of ‘long’ or ‘short’ Gs isoforms (GsαL and GsαS), or in the amounts of Gi 1 + 2 α-subunit (Giα1 + 2). Nor was any difference found in the abundance of the β-subunit of G-proteins. No ‘other’ G-protein (Go) was detectable in these samples by immunoblotting. 5. We conclude that the phenomenon of receptor cross-regulation which we have previously observed in human right atrial appendage is unlikely to be explained by quantitative changes at the G-protein level.

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