scholarly journals Signal transmission via G protein-coupled receptors in the light of rhodopsin structure determination.

2001 ◽  
Vol 48 (4) ◽  
pp. 1203-1207 ◽  
Author(s):  
J Ciarkowski ◽  
P Drabik ◽  
A Giełdoń ◽  
R Kaźmierkiewicz ◽  
R Slusarz
Keyword(s):  
G Protein ◽  
G Proteins ◽  
Structure Determination ◽  
Signal Transmission ◽  
G Protein Coupled Receptors ◽  
Atomic Resolution ◽  
Gtp Binding ◽  
External Signals ◽  
G Protein Coupled ◽  
Experimental Structure

G protein-coupled receptors (GPCRs) transducing diverse external signals to cells via activation of heterotrimeric GTP-binding (G) proteins, estimated to mediate actions of 60% of drugs, had been resistant to structure determination until summer 2000. The first atomic-resolution experimental structure of a GPCR, that of dark (inactive) rhodopsin, thus provides a trustworthy 3D prototype for antagonist-bound forms of this huge family of proteins. In this work, our former theoretical GPCR models are evaluated against the new experimental template. Subsequently, a working hypothesis regarding the signal transduction mechanism by GPCRs is presented.

scholarly journals Signaling from G Protein-coupled Receptors to ERK5/Big MAPK 1 Involves Gαqand Gα12/13Families of Heterotrimeric G Proteins

2000 ◽  
Vol 275 (28) ◽  
pp. 21730-21736 ◽  
Author(s):  
Shigetomo Fukuhara ◽  
Maria Julia Marinissen ◽  
Mario Chiariello ◽  
J. Silvio Gutkind
Keyword(s):  
G Protein ◽  
G Proteins ◽  
G Protein Coupled Receptors ◽  
Heterotrimeric G Proteins ◽  
G Protein Coupled

New thoughts on the role of the βγ subunit in G protein signal transduction

2000 ◽  
Vol 78 (5) ◽  
pp. 537-550 ◽  
Author(s):  
Barbara Vanderbeld ◽  
Gregory M Kelly
Keyword(s):  
Signal Transduction ◽  
G Protein ◽  
G Proteins ◽  
G Protein Coupled Receptors ◽  
Limited Information ◽  
Α Subunit ◽  
Downstream Effectors ◽  
Receptor Signal ◽  
G Protein Coupled

Heterotrimeric G proteins are involved in numerous biological processes, where they mediate signal transduction from agonist-bound G-protein-coupled receptors to a variety of intracellular effector molecules and ion channels. G proteins consist of two signaling moieties: a GTP-bound α subunit and a βγ heterodimer. The βγ dimer, recently credited as a significant modulator of G-protein-mediated cellular responses, is postulated to be a major determinant of signaling fidelity between G-protein-coupled receptors and downstream effectors. In this review we have focused on the role of βγ signaling and have included examples to demonstrate the heterogeneity in the heterodimer composition and its implications in signaling fidelity. We also present an overview of some of the effectors regulated by βγ and draw attention to the fact that, although G proteins and their associated receptors play an instrumental role in development, there is rather limited information on βγ signaling in embryogenesis.Key words: G protein, βγ subunit, G-protein-coupled receptor, signal transduction, adenylyl cyclase.

scholarly journals Signaling by G protein coupled receptors and G proteins: a perspective

Oncogene ◽  
2001 ◽  
Vol 20 (13) ◽  
pp. 1530-1531 ◽  
Author(s):  
N Dhanasekaran ◽  
J Silvio Gutkind
Keyword(s):  
G Protein ◽  
G Proteins ◽  
G Protein Coupled Receptors ◽  
G Protein Coupled

scholarly journals Regulatory mechanisms that modulate signalling by G-protein-coupled receptors

1997 ◽  
Vol 322 (1) ◽  
pp. 1-18 ◽  
Author(s):  
Stephan K. BÖHM ◽  
Eileen F. GRADY ◽  
Nigel W. BUNNETT
Keyword(s):  
G Protein ◽  
G Proteins ◽  
Extracellular Fluid ◽  
Cellular Responses ◽  
Drug Tolerance ◽  
G Protein Coupled Receptors ◽  
Regulatory Mechanisms ◽  
Receptor Desensitization ◽  
Down Regulation ◽  
G Protein Coupled

The large and functionally diverse group of G-protein-coupled receptors includes receptors for many different signalling molecules, including peptide and non-peptide hormones and neurotransmitters, chemokines, prostanoids and proteinases. Their principal function is to transmit information about the extracellular environment to the interior of the cell by interacting with the heterotrimeric G-proteins, and they thereby participate in many aspects of regulation. Cellular responses to agonists of these receptors are usually rapidly attenuated. Mechanisms of signal attenuation include removal of agonists from the extracellular fluid, receptor desensitization, endocytosis and down-regulation. Agonists are removed by dilution, uptake by transporters and enzymic degradation. Receptor desensitization is mediated by receptor phosphorylation by G-protein receptor kinases and second-messenger kinases, interaction of phosphorylated receptors with arrestins and receptor uncoupling from G-proteins. Agonist-induced receptor endocytosis also contributes to desensitization by depleting the cell surface of high-affinity receptors, and recycling of internalized receptors contributes to resensitization of cellular responses. Receptor down-regulation is a form of desensitization that occurs during continuous, long-term exposure of cells to receptor agonists. Down-regulation, which may occur during the development of drug tolerance, is characterized by depletion of the cellular receptor content, and is probably mediated by alterations in the rates of receptor degradation and synthesis. These regulatory mechanisms are important, as they govern the ability of cells to respond to agonists. A greater understanding of the mechanisms that modulate signalling may lead to the development of new therapies and may help to explain the mechanism of drug tolerance.

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