Abstract
We have summarized those bioenergetical processes which we applied to GPCR signalling, and presented a new model for transmembrane signal transduction mediated via (ligand-induced) GPCR and G protein activation. The classical model for G protein activation is based on an exchange mechanism followed by GTP hydrolysis. Our new model is based on GTP synthesis from GDP and Pi, also followed by GTP hydrolysis. Because of amplification levels (1) (synthesis) and (3) (exchange) depicted in Figure 7.1, both the classical and our new model will give rise to similar nucleotide exchange patterns.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Kaldenberg-Stasch S, Baden M, Fesseler B et al. Receptor-stimulated guanine nucleotide-triphosphate binding to guanine nucleotide-binding regulatory proteins. Eur J Biochem 1994; 221:25–33.
Wieland T, Kaldenberg-Stasch S, Fesseler B et al. Regulation of G protein function by phosphorylation. Can J Physiol Pharmacol 1994; 72:S5.
Wieland T, Nürnberg B, Ulibarri I et al. Guanine nucleotide-specific phosphate transfer by guanine nucleotide-binding regulatory protein β-subunits. J Biol Chem 1993; 268:18111–18118.
Kowluru A, Seavey SE, Rhodes CJ et al. A novel regulatory mechanism for trimeric GTP-binding proteins in the membrane and secretory granule fractions of human and rodent β cells. Biochem J 1996; 313:97–107.
Leurs R, Smit MJ, Tensen CP et al. Site-directed mutagenesis of histamine H1-receptor reveals a selective interaction of asparagine207 with subclasses of H1 receptor agonists. Biochem Biophys Res Comm 1994; 201:295–301.
Leurs R, Smit MJ, Meerder R et al. Lysine200 located in the fifth transmembrane domain of the histamine H1 receptor interacts with histamine but not all H1 agonists. Biochem Biophys Res Comm 1995; 214:110–117.
ter Laak AM, Timmerman H, Leurs R et al. Modelling and mutations studies on the histamine H1 receptor agonist binding site reveal different binding modes for H1 agonists; Asp116 (TM3) has a constitutive role in receptor stimulation. J Comp-Aided Mol Design 1995; 9:319–330.
Wiens BL, Nichols DE, Mailman RB et al. Multiple determinants of agonist efficacy at dopamine D2 receptors. Soc Neurosci Abstracts 1994; 20:524.
Hausdorff WP, Hnatowich M, O’Dowd BF et al. A mutation of the β2 adrenergic receptor impairs agonist activation of adenylate cyclase without affecting high affinity agonist binding. J Biol Chem 1990; 265:1388–1393.
Ernst OP, Hofmann KP, Sakmar TP. Characterization of rhodop-sin mutants that bind transducin but fail to induce GTP nucleotide uptake. J Biol Chem 1995; 270:10580–10586.
Samama P, Cotecchia S, Costa T et al. A mutation-induced activated state of the β2 adrenergic receptor. Extending the ternary complex model. J Biol Chem 1993; 268:4625–4636.
Ross EM. G protein-coupled receptors: structural basis of selective signalling. NATO ASI Series, Series H 1991; 52:163–177.
Timms D, Wilkinson AJ, Kelly DR et al. Interactions of Tyr377 in a ligand-activation model of signal transmission through β1 adrenoceptor α-helices. Int J Quant Chem: Quant Biol Symp 1992; 19:197–215.
Timms D, Wilkinson AJ, Kelly DR et al. Ligand-activated transmembrane proton transfer in β1 adrenergic and m2 muscarinic receptors. Receptors and Channels 1994; 2:107–119.
Coleman DE, Sprang SR. How G proteins work: a continuing story Trends Biochem Sci 1996; 21:41–44.
Clapham DE. The G protein nanomachine. Nature 1996; 379:297–299.
Andersson H, von Heijne G. Membrane protein topology effects of ΔμH+ on the translocation of charged residues explain the ‘positive inside’ rule. EMBO J 1994; 13:2267–2272.
von Heijne G. The distribution of positively charged residues in bacterial inner membrane proteins correlates with the trans-membrane topology. EMBO J 1986; 5:3021–3027.
Seifert R, Hagelücken A, Höer A et al. The H1 receptor agonist 2-(3-chlorophenyl)histamine activates Gi proteins in HL-60 cells through a mechanism that is independent of known histamine receptor subtypes. Mol Pharmacol 1994; 45:578–586.
Hagelücken A, Grünbaum L, Klinker JF et al. Histamine receptor-dependent and/or-independent activation of guanine nucleotide-binding proteins by histamine and 2-substituted histamine derivatives in human leukemia (HL-60) and human erythroleukemia (HEL) cells. Biochem Pharmacol 1995; 49:901–914.
Morowitz HJ. Proton semiconductors and energy transduction in biological systems. Am J Physiol 1978; 235:R99-R114.
Author information
Authors and Affiliations
Rights and permissions
Copyright information
© 1997 Springer Science+Business Media Dordrecht
About this chapter
Cite this chapter
Nederkoorn, P.H.J., Timmerman, H., den Kelder, G.M.DO. (1997). Conclusions and Future Perspectives. In: Signal Transduction by G Protein-Coupled Receptors. Molecular Biology Intelligence Unit. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-1407-3_9
Download citation
DOI: https://doi.org/10.1007/978-1-4684-1407-3_9
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4684-1409-7
Online ISBN: 978-1-4684-1407-3
eBook Packages: Springer Book Archive