Abstract
Heterotrimeric guanine nucleotide-binding regulatory proteins (G proteins) serve to transduce information from agonist-bound receptors to effector enzymes or ion channels. Current models of G protein activation-deactivation indicate that the oligomeric GDP-bound form must undergo release of GDP, bind GTP and undergo subunit dissociation, in order to be in active form (GTP bound α subunits and free βγ dimers) and to regulate effectors. The effect of receptor occupation by an agonist is generally accepted to be promotion of guanine nucleotide exchange thus allowing activation of the G protein. Recent studies indicate that transphosphorylation leading to the formation of GTP from GDP and ATP in the close vicinity, or even at the G protein, catalysed by membrane-associated nucleoside diphosphate kinase, may further activate G proteins. This activation is demonstrated by a decreased affinity of G protein-coupled receptors for agonists and an increased response of G protein coupled effectors. In addition, a phosphorylation of G protein β subunits and consequent phosphate transfer reaction resulting in G protein activation has also been demonstrated. Finally, endogenously formed GTP was preferentially effective in activating some G proteins compared to exogenous GTP. The aim of this report is to present an overview of the evidence to date for a transphosphorylation as a means of G protein activation (see also refs [1 and 2] for reviews).
Recipient of Servier Investigator Award
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Otero AD: Transphosphorylation and G protein activation. Biochem Pharmacol 39: 1399–1404, 1990
Lacombe ML, Jakobs KH: Nucleoside diphosphate kinases as potential new targets for control of development and cancer. Tr Pharmacol Sci 13:46–48, 1992
Parks RE, Agarwal RP: Nucleoside diphosphokinases In: Boyer PD (ed.) The Enzymes (3rd. edition), Academic Press, New York & London, 1973, pp 307–303
Moréra S, Lascu I, Dumas C, LeBras G, Briozzi P, Véron M, Janin J: Adenosine 5′-diphosphate binding and the active site of nucleoside diphophate kinase. Biochemistry 33: 459–467, 1994
Cherfils J, Moréra S, Lascu I, Véron M, Janin J: X-ray structure of nucleoside diphophate kinase complexed with thymidine diphophate and Mg2+ at 2- Å resolution. Biochemistry 33: 9062–9069, 1994
Bominaar AA, Molijn AC, Pestel M, Veron M, Van Haastert PJM: Activation of G-proteins by receptor-stimulated nucleoside diphophate kinase in Dictyostelium. EMBO J 12: 2275–2279, 1993
Kowluru A, Metz SA: Characterization of nucleoside diphosphokinase in human and rodent pancreatic β cells: evidence for its role in the formation of guanosine triphosphate, a permissive factor for nutrient-induced insulin secretion. Biochemistry 33: 12495–12503, 1994
Kimura N, Shimada N: GDP does not mediate but rather inhibits hormonal signal to adenylate cyclase. J Biol Chem 258: 2278–2283,1983
Ohtsuki K, Yokoyama M, Uesaka H: Physiological correlation between nucleoside-diphosphate kinases and the 21-kDa guanine-nucleotide binding proteins copurified with the enzymes from the cell membrane fractions of Ehrlich ascites tumor cells. Biochim Biophys Acta 929: 231–238, 1987
Kimura N, Shimada N: Direct interaction between membrane-associated nucleoside diphosphate kinase and GTP-binding protein (Gs), and its regulation by hormones and guanine nucleotides. Biochem Biophys Res Comm 151: 248–256, 1988
Wieland T, Jakobs KH: Receptor-regulated formation of GTP[γS] with subsequent persistant Gs-protein activation in membranes of human platelets. FEBS Lett 245: 189–193, 1989
Blevins GT, Van de Westerlo EMA, Williams JA: Nucleoside diphosphate kinase associated with rat pancreatic membranes regulates CCK receptor affinity. Am J Physiol 267: G866-G874, 1994
Rodbell M, Krans HMJ, Pokl SL, Birnbaumer L: The glucagon-sensitive adenyl cyclase system in plasma membranes of rat liver. IV. Binding of glucagon: effect of guanyl nucleotides. J Biol Chem 246, 1873–1876, 1971
Wieland T, Bremerich J, Gierschik P, Jakobs KH: Contribution of nucleoside diphosphokinase to guanine nucleotide regulation of agonist binding to formyl peptide receptors. Eur J Pharmacol 208: 17–23, 1991
Wieland T, Jakobs KH: Evidence for nucleoside diphosphokinase-dependent channelling of guanosine 5′-(γ-thio)triphosphate to guanine nucleotide-binding proteins. Mol Pharmacol 42: 731–735, 1992
Jakobs KH, Wieland T: Evidence for receptor-regulated phosphotransfer reactions involved in activation of the adenylate cyclase inhibitory G protein in human platelet membranes. Eur J Biochem 183: 115–121, 1989
Seifert R, Rosenthal W, Schultz G, Wieland T, Gierschick P, Jakobs KH: The role of nucleoside-diphosphate kinase reactions in G protein activation of NADPH oxidase by guanine and adenine nucleotides. Eur J Biochem 175: 51–55, 1988
Otero AS, Breitwieser GE, Szabo G: Activation of muscarinic potassium currents by ATPγS in atrial cells. Science 242: 443–445, 1988
Heidbüchel H, Callewaert G, Vereecke J, Carmeliet E: Acetylcholine-mediated K+ channel activity in guinea-pig atrial cells is supported by nucleoside diphosphate kinase. Pflugers Archiv 422: 316–324, 1993
Gross RA, Uhler MD, Macdonald RL: The reduction of neuronal calcium currents by ATP-γ-S is mediated by a G protein and occurs independently of cyclic AMP-dependent protein kinase. Brain Res 535: 214–220, 1990
Fan XT, Sherwood JL, Haslam RJ: Stimulation of phosphlipase D in rabbit platelet membranes by nucleoside triphosphates and by phosphocreatine: roles of membrane-bound GDP, nucleoside diphophate kinase and creatine kinase. Biochem J 299: 701–709, 1994
Vu ND, Wagner PD: Stimulation of secretion in permeabilised PC 12 cells by adenosine 5′[γ-thio]triphosphate: possible involvement of nucleoside diphosphate kinase. Biochem J 296: 169–174, 1993
Kikkawa S, Takahashi K, Takahashi K, Shimada N, Ui M, Kimura N, Katada T: Activation of nucleoside diphosphate kinase by mastoparan, a peptide isolated from wasp venom. FEBS Lett 305: 237–240, 1992
Klinker JF, Hagelüken A, Grünbaum L, Heilmann I, Nürnberg B, Harhammer R, Offermans S, Schwaner I, Ervans J, Wenzel-Seifert K, Muller T, Seifert R: Mastoparan may activate GTP hydrolysis by Gi-proteins in HL-60 membranes indirectly through interaction with nucleoside diphosphate kinase. Biochem J 304: 377–383, 1994
Higashijima T, Burnier J, Ross EM: Regulation of Gi. and Go by mastoparan, related amphilic peptides and hydrophobic amines. J Biol Chem265: 14176–14186, 1990
Ross EM, Higashijima T: Regulation of G-protein activation by mastoparans and other cationic peptides. Meth Enzymol 237: 26–37, 1994
Kowluru A, Seavey SE, Rabaglia ME, Metz SA: Non-specific stimulatory effects of mastoparan on pancreatic islet nucleoside diphosphokinase activity: dissociation from insulin secretion. Biochem Pharmacol 49: 263–266, 1995
Wieland T, Ulibarri I, Gierschik P, Jakobs KH: Activation of signal-transducing guaninenucleotide-binding regulatory proteins by guano-sine 5′-[γ-thio]triphophate. Eur J Biochem 196: 707–716, 1991
Wieland T, Ronzani M, Jakobs KH: Stimulation and inhibition of human platelet adenylylcyclase by thiophosphorylated transducin βγ-subunits. J Biol Chem 267: 20791–20797, 1992
Wieland T, Nurnberg B, Ulibarri I, Kaldenberg-Stasch S, Schulz G, Jakobs KH: Guanine nucleotide-specific phosphate transfer by guanine nucleotide-binding regulatory protein β-subunits. J Biol Chem 268: 18111–18118, 1993
Kleineke J, Duls C, Soling HD: Subcellular compartmentation of guanine nucleotides and functional relationships between the adenine and guanine nucleotide systems in isolated hepatocytes. FEBS Lett 107:197–202, 1979
Gilman AG G proteins: transducers of receptor-generated signals: Ann Rev Biochem 56: 615–49, 1987
Birnbaumer L, Birnbaumer M: Signal transductiom by G proteins: 1994 edition. J Rec Sig Tran Res 15: 213–352, 1995
Neer EJ: Heterotrimeric G proteins: organizers of transmembrane signals. Cell 80: 249–257, 1995
Niroomand F, Bangert M, Philipps C, Rauch B: Muscarinic receptor-mediated inhibition of GDP-activated adenylyl cyclase suggests a direct interaction of inhibitory guanine nucleotide-binding proteins and adenylyl cyclase. Mol Pharmacol 43: 90–95, 1993
Niroomand F, Piacentini L, Mura R, Rauch B: Receptor independent activation of cardiac adenylyl cyclase by GDP and a membrane-associated nucleoside diphophate kinase. J Clin Invest Med 43(suppl 2);354, 1995
Kaldenberg-Stasch S, Baden M, Fesseler B, Jakobs KH, Wieland T: Receptor-stimulated guanine-nucleotide-triphosphate binding to guanine-nucleotide-binding regulatory proteins. Nucleotide exchange and β-subunit-mediated phosphotransfer reactions. Eur J Biochem 221: 25–33, 1994
Ohtsuki K, Yokoyama M: Direct activation of guanine nucleotide binding proteins through a high-energy phosphate-transfer by nucleoside diphosphate-kinase. Biochem Biophys Res Comm 148: 300–307, 1987
Kikkawa S, Takahashi K, Takahashi K, Shimada N, Ui M, Kimura N, Katada T: Phosphorylation of GDP into GTP by nucleoside diphosphate kinase on the GTP-binding proteins. J Biol Chem 265: 21536–21540, 1990
Randazzo PA, Northup JK, Kahn RA: Activation of a small GTP-binding protein by nucleoside diphosphate kinase. Science 254: 850–853, 1991
Ref. 39 additions and corrections. J Biol Chem 266: 12795, 1991
Ref. 40 conclusion withdrawn. Science 557: 862, 1992
Randazzo PA, Northup JK, Kahn RA: Regulatory GTP-binding proteins (ADP-ribosylation factor, Gt and RAS) are not activated directly by nucleoside diphosphate kinase. J Biol Chem 267: 18182–18189, 1992
Bristow MR, Ginsburg R, Minobe W, Cubiciotti RS, Sageman WS, Lurie K, Billingham ME, Harrison DC, Stinson EB: Decreased catecholamine sensitivity and beta-adrenergic-receptor density in failing human hearts. New Eng J Med 307: 205–211, 1982
Lohse MJ: Molecular mechanisms of membrane receptor desensitization. Biochim Biophys Acta 1179: 171–188, 1993
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1996 Kluwer Academic Publishers
About this chapter
Cite this chapter
Piacentini, L., Niroomand, F. (1996). Phosphotransfer reactions as a means of G protein activation. In: Lamers, J.M.J., Verdouw, P.D. (eds) Biochemistry of Signal Transduction in Myocardium. Developments in Molecular and Cellular Biochemistry, vol 17. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-1275-8_7
Download citation
DOI: https://doi.org/10.1007/978-1-4613-1275-8_7
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4612-8544-1
Online ISBN: 978-1-4613-1275-8
eBook Packages: Springer Book Archive