G Proteins

A Family of Signal-Transducing Molecules
  • Eva J. Neer
Part of the New Horizons in Therapeutics book series (NHTH)


The signals from many receptors for hormones and neurotransmitters are sent through the plasma membrane by a set of heterotrimeric GTP-binding proteins composed of a GTP-binding α subunit and a βγ subunit that is a nondissociable dimer made up of two different polypeptides (for recent reviews, see Gilman, 1987; Stryer and Bourne, 1986; Lochrie and Simon, 1988; Neer and Clapham, 1988). The receptors on the cell surface are extremely specific for their ligands, which have very low affinities for heterologous receptors. Thus, there is very little cross-talk due to agonist binding at an inappropriate receptor. However, the next steps in the cascade appear to be less precise. Within a single cell, several separate receptors can often regulate each final pathway. For example, in the heart, acetylcholine and adenosine receptors appear to regulate the same K+ channel (Kurachi et al., 1986).


Adenylate Cyclase Adenylyl Cyclase Human Fetal Tissue Guanine Nucleoside Neonatal Cardiocytes 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Buxton, I. L., and Brunton, L. L., 1983, Compartments of cyclic AMP and protein kinase in mammalian cardiomyocytes, J. Biol. Chem. 258: 10233–10239.PubMedGoogle Scholar
  2. Carlson, K. E., Woolkalis, M. J., Newhouse, M. G., and Manning, D. R., 1986, Fractionation of the 3 subunit common to guanine nucleotide-binding regulatory proteins with the cytoskeleton, Mol. Pharmacol. 30: 463–468.PubMedGoogle Scholar
  3. Codina, Y., Yatani, A., Grenet, D., Brown, A. M., and Bimbaumer, L., 1987, The a subunit of the GTP-binding protein Gk opens atrial potassium channels, Science 238: 1288–1291.PubMedCrossRefGoogle Scholar
  4. Dominguez, P., Velasco, G., Barros, F., and Lazo, P. S., 1987, Intestinal brush border membranes contain regulatory subunits of adenylyl cyclase, Proc. Nad. Acad. Sci. USA 84: 6965–6969.CrossRefGoogle Scholar
  5. Dufau, M. L., Homer, J. A., Hayashi, K., Tsuruhara, T., Conn, P. M., and Catt, K. J., 1978, Actions of choleragen and gonadotropin in isolated Leydig cells, J. Biol. Chem. 253: 3721–3729.PubMedGoogle Scholar
  6. Florio, V. A., and Sternweis, P. C., 1985, Reconstitution of resolved muscarinic cholinergic receptors with purified GTP-binding proteins, J. Biol. Chem. 260: 3477–3483.PubMedGoogle Scholar
  7. Fung, B. K. K., Hurley, J. B., and Stryer, L., 1981, Flow of information in the light-triggered cyclic nucleotide cascade of vision, Proc. Natl. Acad. Sci. USA 78: 152–56.PubMedCrossRefGoogle Scholar
  8. Garrett, M. D., Self, A. J., van Oers, C., and Hall, A., 1989, Identification of distinct cytoplasmic targets for ras/R-ras and rho regulatory proteins, J. Biol. Chem. 264: 10–13.PubMedGoogle Scholar
  9. Gilman, A. G., 1987, G-proteins: Transducers of receptor-generated signals, Annu. Rev. Biochem. 56: 615–650.PubMedCrossRefGoogle Scholar
  10. Graziano, M. P., Casey, P. J., and Gilman, A. G., 1987, Expression of cDNAs for G-proteins in E. coli, J. Biol. Chem. 262: 11375–11381.PubMedGoogle Scholar
  11. Hescheler, J., Rosenthal, W., Trautwein, W., and Schultz, G., 1987, The GTP-binding protein Go regulates neuronal calcium channels, Nature (London) 325: 445–447.CrossRefGoogle Scholar
  12. Huff, R. M., Axton, J. M., and Neer, E. J., 1985, Physical and immunological characterization of a guanine nucleotide-binding protein purified from bovine cerebral cortex, J. Biol. Chem. 260: 10864–10871.PubMedGoogle Scholar
  13. Insel, P. A., and Kennedy, M. S., 1978, Colchichine potentiates 3-adrenoreceptor-stimulated cyclic AMP in lymphoma cells by an action distal to the receptor, Nature 273: 471–473.PubMedCrossRefGoogle Scholar
  14. Jelsema, C. L., and Axelrod, J., 1987, Stimulation of phospholipase A2 activity in bovine rod outer segments by the ßy subunits of transducin and its inhibition by the a subunit, Proc. Natl. Acad. Sci. USA 84: 3623–3627.PubMedCrossRefGoogle Scholar
  15. Jones, D. T., and Reed, R. R., 1987, Molecular cloning of five GTP-binding protein cDNA species from rat olfactory neuroepithelium, J. Biol. Chem. 262: 14241–14249.PubMedGoogle Scholar
  16. Kim, D., Lewis, D. L., Graziadei, Neer, E. J., Bar-Sagi, D., and Clapham, D. E., 1989, G-protein 3y-subunits activate the cardiac muscarinic K+-channel via phospholipase A2, Nature 337: 557–560.PubMedCrossRefGoogle Scholar
  17. Kim, S. Y., Ang, S-L., Bloch, D., Bloch, K., Kawahara, Y., Lee, R. L., Tolman, C., Seidman, J. G., and Neer, E. J., 1988, Identification of cDNA encoding an additional a subunit of a human GTP-binding protein, Proc. Natl. Acad. Sci. USA 85: 4153–4157.PubMedCrossRefGoogle Scholar
  18. Kurachi, Y., Nakajima, T., and Sugimoto, T., 1986, On the mechanism of activation of muscarinic K+ channels by adenosine in isolated atrial cells: involvement of GTP-binding proteins, Pflügers Arch. 407: 264–274.PubMedCrossRefGoogle Scholar
  19. Lerea, C. L., Somers, D. E., Hurley, J. B., Klock, I. B., and Bunt-Milam, A. M., 1986, Identification of specific transducin a subunits in retinal rod and cone photoreceptors, Science 234: 7780.CrossRefGoogle Scholar
  20. Lochrie, M. A., and Simon, M. I., 1988, G-protein multiplicity in signal transduction systems, Biochemistry 27: 4957–4965.PubMedCrossRefGoogle Scholar
  21. Logothetis, D. E., Kurachi, Y., Galper, J., Neer, E. J., and Clapham, D. E., 1987, The 3y subunits of GTP-binding proteins activate the muscarinic K+ channel in heart, Nature 325: 321–326.PubMedCrossRefGoogle Scholar
  22. Logothetis, D. E., Northup, J., Neer, E. J., and Clapham, D. E., 1988, Specificity of action of guanine nucleotide-binding regulatory protein subunits on the cardiac muscarinic K + channels, Proc. Natl. Acad. Sci. 85: 5814–5818.PubMedCrossRefGoogle Scholar
  23. Neer, E. J., and Clapham, D. E., 1988, Roles of G-proteins in transmembrane signalling, Nature (London) 333: 129–134.CrossRefGoogle Scholar
  24. Neer, E. J., Lok, J. M., and Wolf, L. G., 1984, Purification and properties of the inhibitory guanine nucleotide regulatory unit of brain adenylate cyclase, J. Biol.Chem. 259: 14222–14229.PubMedGoogle Scholar
  25. Northup, J. K., Smigel, M. D., Sternweis, P. C., and Gilman, A. G., 1983, The subunits of the stimulatory regulatory component of adenylate cyclase, J. Biol. Chem. 258: 11369–11376.PubMedGoogle Scholar
  26. O’Farrell, P. Z., Goodman, H. M., and O’Farrell, P. H., 1977, High-resolution two-dimensional electrophoresis of basic as well as acidic proteins, Cell 12: 1133–1142.PubMedCrossRefGoogle Scholar
  27. Rasenick, M. M., Stein, P. J., and Bitensky, M. W., 1981, The regulatory subunit of adenylate cyclase interacts with cytoskeletal components, Nature 294: 560–562.PubMedCrossRefGoogle Scholar
  28. Schlatz, L. J., Schwartz, I. L., Kinne-Saffran, E., and Kinne, R., 1975, Distribution of parathyroid hormone-stimulated adenylate cyclase in plasma membranes in cells of the kidney cortex, J. Mem. Biol. 24: 131–144.CrossRefGoogle Scholar
  29. Silbert, S., Michel, T., Lee, R., and Neer, E. J., 1990, Differential degradation rates of the G protein ao in cultured cardiac and pituitary cells, J. Biol. Chem. 265: 3102–3105.PubMedGoogle Scholar
  30. Sternweis, P. C., and Robishaw, J., 1984, Isolation of two proteins with high affinity for guanine nucleotides from membranes of bovine brain, J. Biol. Chem. 259: 13806–13813.PubMedGoogle Scholar
  31. Stryer, L., and Boume, H. R., 1986, G-proteins: A family of signal transducers, Annu. Rev. Cell Biol. 2: 391–419.PubMedCrossRefGoogle Scholar
  32. Tolkovsky, A. M., Braun, S., and Levitski, A., 1982, Kinetics of interaction between the 3-receptor, the GTP regulatory protein, and the catalytic unit of turkey erythrocyte adenylate cyclase, Proc. Natl. Acad. Sci. USA 79: 213–217.PubMedCrossRefGoogle Scholar
  33. Trahey, M., and McCormick, F., 1987, A cytoplasmic protein stimulates normal N-ras p21 GTPase, but does not affect oncogene mutants, Science 238: 542–545.PubMedCrossRefGoogle Scholar
  34. VanDongen, A. M., Codina, J., Olate, J., Mattera, R., Joho, R., Birnbaumer, L., and Brown, A. M., 1988, Newly identified brain potassium channels gated by the guanine nucleotide binding protein Go, Science 242: 1433–1437.PubMedCrossRefGoogle Scholar
  35. Whiteway, M., Hougan, L., Dignard, D., Thomas, D. Y., Bell, L., Saari, G. C., Grant, F. J., O’Hara, P., and MacKay, V. L., 1989, The STE4 and STE18 genes of yeast encode potential ß and y subunits of the mating factor receptor-coupled G protein, Cell 56: 467–477.PubMedCrossRefGoogle Scholar
  36. Worley, P. F., Baraban, J. M., Van Dop, C., Neer, E. J., and Snyder, S., 1986, Go, a guanine nucleotide-binding protein: Immunohistochemical localization in rat brain resembles distribution of second messenger systems, Proc. Natl. Acad. Sci. USA 83: 4561–4565.PubMedCrossRefGoogle Scholar
  37. Yatani, A., Mattera, R., Codina, J., Graf, R., Okabe, K., Padrell, E., Iyengar, R., Brown, A. M., and Birnbaumer, L., 1988, The G protein-gated atrial K+ channel is stimulated by three distinct G, alpha-subunits, Nature 336: 680–682.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Eva J. Neer
    • 1
  1. 1.Department of MedicineBrigham and Women’s Hospital and Harvard Medical SchoolBostonUSA

Personalised recommendations