SpringerLink
Log in

Receptors and G proteins as primary components of transmembrane signal transduction

Part 2. G proteins: structure and function

  • Review
  • Published:
Journal of Molecular Medicine Aims and scope Submit manuscript

Abstract

Seven-transmembrane receptors signal through nucleotide-binding proteins (G proteins) into the cell. G proteins are membrane-associated proteins composed of three subunits termed α, β and γ, of which the Gα subunit classifies the heterotrimer. So far, 23 different mammalian Gα subunits are known, which are grouped in four subfamilies (Gs, Gi, Gq, G12) on the basis of their amino acid similarity. They carry an endogenous GTPase activity allowing reversible functional coupling between ligand-bound receptors and effectors such as enzymes and ion channels. In addition, five Gβ and seven Gγ subunits have been identified which form tightly associated βγ heterodimers. Upon activation by a ligand-bound receptor the G protein dissociates into Gα and Gβγ, which both transmit signal by interacting with effectors. On the G protein level, specificity and selectivity of the incoming signal is accomplished by G protein trimers composed of distinct subunits. On the other hand, many receptors have been shown to activate different G proteins, thereby regulating diverse signal transduction pathways.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

CT :

Cholera toxin

PT :

Pertussis toxin

References

  1. Koesling D, Böhme E, Schultz G (1993) Guanylyl cyclases as effectors of hormone and neurotransmitter receptors. In: Hucho F (ed) Neurotransmitter receptors. Elsevier, pp 325–338

  2. Jan LY, Jan YN (1992) Tracing the roots of ion channels. Cell 69:715–718

    Article  CAS  PubMed  Google Scholar 

  3. Unwin N (1993) Neurotransmitter action: opening of ligandgated ion channels. Neuron [Suppl] 10:31–41

    Article  Google Scholar 

  4. Schlessinger J, Ullrich A (1992) Growth factor signaling by receptor tyrosine kinase. Neuron 9:383–391

    Article  CAS  PubMed  Google Scholar 

  5. Egan SE, Weinberg A (1993) The pathway to signal achievement. Nature (London) 365:781–783

    Article  CAS  Google Scholar 

  6. Charbonneau H, Tonks NK (1992) 1002 protein phosphatases? Annu Rev Cell Biol 8:463–493

    Article  CAS  PubMed  Google Scholar 

  7. Garbers DL (1992) Guanylyl cyclase receptors and their endocrine, paracrine, and autocrine ligands. Cell 71:1–4

    Article  CAS  PubMed  Google Scholar 

  8. Gudermann T, Nürnberg B, Schultz G (1995) Receptors and G proteins as primary components of transmembrane signal transduction. I. G protein-coupled receptores: structure and function. J Mol Med 73:51–63

    Article  CAS  PubMed  Google Scholar 

  9. Watson S, Arkinstall S (1994) The G protein linked receptor facts book. Academic, New York

    Google Scholar 

  10. Schultz G (1994) G proteins involved in hormonal regulations of the cytoplasmatic calcium concentrations. Ernst Schering Research Foundation, vol 19, Berlin

    Google Scholar 

  11. Sternweis PC, Smrcka AV (1992) Regulation of phospholipase C by G proteins. Trends Biochem Sci 17:502–506

    Article  CAS  PubMed  Google Scholar 

  12. Iyengar R (1993) Molecular and functional diversity of mammalian Gs-stimulated adenylyl cyclases. FASEB J 7:768–775

    CAS  PubMed  Google Scholar 

  13. Tang WJ, Gilman AG (1992) Adenylyl cyclases. Cell 70:869–972

    Article  CAS  PubMed  Google Scholar 

  14. Dickey BF, Birnbaumer L (eds) (1993) Handbook of experimental pharmacology, vol 108. Springer, Berlin Heidelberg New York

    Google Scholar 

  15. Bourne HR, Sanders DA, McCormick F (1990) The GTPase superfamily: a conserved switch for diverse cell functions. Nature (London) 348:125–132

    Article  CAS  Google Scholar 

  16. Bourne HR, Sanders DA, McCormick F (1991) The GTPase superfamily: a conserved switch for diverse cell functions. Nature (London) 349:117–127

    Article  CAS  Google Scholar 

  17. Rodbell M, Krans HMJ, Pohl SL, Birnbaumer L (1971) The glucogon-sensitive adenyl cyclase system in plasma membranes of rat liver. IV. Binding of glucagon: effect of guanyl nucleotides. J Biol Chem 246:1872–1876

    CAS  PubMed  Google Scholar 

  18. Bourne HR, Nicoll R (1993) Molecular machines integrate coincident synaptic signals. Neuron [Suppl] 10:65–75

    Google Scholar 

  19. Clapham DE, Neer EJ (1993) New roles for G protein βγ-dimers in transmembrane signalling. Nature (London) 365:403–406

    Article  CAS  Google Scholar 

  20. Leyte A, Barr FA, Kehlenbach RH, Huttner WB (1992) Multiple trimeric G proteins on the trans-golgi network exert stimulatory and inhibitory effects on secretory vescle formation. EMBO J 11:4795–4804

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Pimplikar SW, Simons K (1993) Regulation of apical transport in epithelial cells by a Gs class of heterotrimeric G protein. Nature (London) 362:456–458

    Article  CAS  Google Scholar 

  22. Bomsel M, Mostov K (1992) Role of heterotrimeric G proteins in membrane traffic. Mol Biol Cell 3:1317–1328

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Barr FA, Leyte A, Huttner WB (1992) Trimeric G proteins and vesicle formation. Trends Cell Biol 2:91–94

    Article  CAS  PubMed  Google Scholar 

  24. Birnbaumer L (1992) Receptor-to-effector signaling through G proteins: roles for βγ dimers as well as α subunits. Cell 71:1069–1072

    Article  CAS  PubMed  Google Scholar 

  25. Hepler JR, Gilman AG (1992) G proteins. Trends Biochem Sci 17:383–387

    Article  CAS  PubMed  Google Scholar 

  26. Wilkie TM, Gilbert DJ, Olsen AS, Chen XN, Amatruda TT, Korenberg JR, Trask BJ, de Jong P, Reed RR, Simon MI, Jenkins NA, Copeland NG (1992) Evolution of the mammalian G protein α subunit multigene family. Nature Genetics 1:85–91

    Article  CAS  PubMed  Google Scholar 

  27. Gilman AG (1987) G proteins: transducers of receptor-generated signals. Annu Rev Biochem 56:615–649

    Article  CAS  PubMed  Google Scholar 

  28. Higashijima T, Ferguson KM, Sternweis PC, Smigel MD, Gilman AG (1987) Effects of Mg2+ and the βγ-subunit complex on the interactions of guanine nucleotides with G proteins. J Biol Chem 262:762–766

    CAS  PubMed  Google Scholar 

  29. Fields TA, Linder ME, Casey PJ (19994) Subtype-specific binding of azidoanilido-GTP by purified G protein α subunits. Biochemistry 33:6877–6883

  30. Laugwitz KL, Spicher K, Schultz G, Offermanns S (1994) Identification of receptor-activated G proteins: selective immunoprecipitation of photolabled G protein α-subunits. Methods Enzymol 237:283–294

    Article  CAS  PubMed  Google Scholar 

  31. Kaldenberg-Stasch S, Baden M, Fessler B, Jakobs KH, Wieland T (1994) Receptor-stimulated guanine nucleoside triphosphate binding to G proteins: nucleotide exchange and β-subunit-mediated phosphotransfer reactions. Eur J Biochem 221:25–33

    Article  CAS  PubMed  Google Scholar 

  32. Sternweis PC (1994) The active role of βγ in signal transduction. Curr Opin Cell Biol 6:198–203

    Article  CAS  PubMed  Google Scholar 

  33. Hille B (1992) G protein-coupled mechanisms and nervous signaling. Neuron 9:187–195 (1992)

    Article  CAS  PubMed  Google Scholar 

  34. Hargrave PA, Hamm HE, Hofmann KP (1993) Interaction of rhodopsin with the G protein, transducin. Bioessays 15:43–50

    Article  CAS  PubMed  Google Scholar 

  35. Nürnberg B (1994) Signaltransduktion durch heterotrimere G Proteine. Pharmazie 49:795–800

    PubMed  Google Scholar 

  36. Gierschik P, Jakobs KH (1992) ADP-ribosylation of signaltransducing guanine nucleotide binding proteins by cholera and pertussis toxin. In: Herken H, Hucho F (eds) Selective neurotoxicity. Handbook of experimental pharmacology, vol 102. Springer, Berlin Heidelberg New York, pp 807–839

    Google Scholar 

  37. Simon MI, Strathmann MP, Gautam N (1991) Diversity of G proteins in signal transduction. Science 252:802–808

    Article  CAS  PubMed  Google Scholar 

  38. Milligan G (1988) Techniques used in the identification and analysis of function of pertussis toxin-sensitive guanine nucleotide binding proteins. Biochem J 255:1–13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Johnson RA, Corbin JD (eds) (1991) Adenylyl cyclase, G proteins and guanylyl cyclase. Methods Enzymol 195

  40. Iyengar R (ed) (1994) Heterotrimeric G proteins. Methods Enzymol 237

  41. Kehlenbach RH, Matthey J, Huttner WB (1995) XLαs is a new type of G protein. Nature (London) 372:804–809

    Article  Google Scholar 

  42. Nürnberg B, Spicher K, Harhammer R, Bosserhoff A, Frank R, Hilz H, Schultz G (1994) Purification of a novel G protein α0-subtype from mammalian brain. Biochem J 300:387–394

    Article  PubMed  PubMed Central  Google Scholar 

  43. Rudolph U, Brabet P, Kaplan J, Hasty P, Bradley A, Birnbaumer L (1993) targeting of the Gi2α gene in IS cells with replacements and insertion vectors. J Recept Res 13:619–629

    Article  CAS  PubMed  Google Scholar 

  44. Mortensen RM, Zubiaur M, Neer EJ, Seidman JG (1991) Embryonic stem cells lacking a functional inhibitory G protein subunit (αi2) produced by gene targeting of both alleles. Proc Natl Acad Sci USA 88:7036–7040

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Montmayeur JP, Borelli E (1994) Targeting of Gαi2 to the golgi by alternative spliced carboxyl-terminal region. Science 263:95–98

    Article  CAS  PubMed  Google Scholar 

  46. Gollasch M, Kleuss C, Hescheler J, Wittig B, Schultz G (1993) Gi2 and protein kinase C are required for thyrotropinreleasing hormone-induced stimulation of voltage-dependent Ca2+ channels in rat pituitary GH3 cells. Proc Natl Acad Sci USA 90:5587–5591

    Article  Google Scholar 

  47. Kleuss C, Hescheler J, Ewel C, Rosenthal W, Schultz G, Wittig B (1991) Assignment of G protein subtypes to specific receptors inducing inhibition of calcium currents. Nature (London) 353:43–48

    Article  CAS  Google Scholar 

  48. Kleuss C, Scherübl H, Hescheler J, Schultz G, Wittig B (1992) Different β subunits determine G protein interaction with transmembrane receptors. Nature (London) 358:424–426

    Article  CAS  Google Scholar 

  49. Kleuss C, Scherübl H, Hescheler J, Schultz G, Wittig B (1993) Selectivity in signal transduction determined by γ subunits of heterotrimeric G proteins. Science 259:832–834

    Article  CAS  PubMed  Google Scholar 

  50. Kalkbrenner F, Degtyar V, Schenker M, Hescheler J, Brendel S, Wittig B, Schultz G (1994) Subunit composition of the G protein coupling galanin receptors to L-type calcium channels. Naunyn Schmiedebergs Arch Pharmacol 349:R13

    Google Scholar 

  51. Nürnberg B, Degtiar VE, Harhammer R, Uhde M, Hescheler J, Schultz G (1994) Hormone-induced G0-subtype-specific inhibition of calcium currents. Naunyn Schmiedebergs Arch Pharmacol 349:R13

    Google Scholar 

  52. Kaupp UB, Koch KW (1992) Role of cGMP and Ca2+ in vertebrate photoreceptor excitation and adaptation. Annu Rev Physiol 54:153–175

    Article  CAS  PubMed  Google Scholar 

  53. Noel JP, Hamm HE, Sigler PB (1993) The 2. 2 Å crystal structure of transducin-α complexed with GTPγS. Nature (London) 366:654–663

    Article  CAS  Google Scholar 

  54. Lambbright DG, Noel JP, Hamm HE, Sigler PB (1994) Structural determinants for actvation of a heterotrimeric G protein. Nature (London) 369:621–628

    Article  Google Scholar 

  55. Coleman DE, Berghuis AM, Lee E, Linder ME, Gilman AG, Sprang SR (1994) Structures of active conformations of Giαl and the mechanism of GTP hydrolysis. Science 265:1405–1412

    Article  CAS  PubMed  Google Scholar 

  56. Goody RS (1994) How G proteins turn off. Nature (London) 372:220–221

    Article  CAS  Google Scholar 

  57. Kleuss C, Raw AS, Lee E, Sprang SR, Gilman AG (1994) Mechanism of GTP hydrolysis by G protein α subunits. Proc Natl Acad Sci USA 91:9828–9831

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Sondek J, Lambbright DG, Noel JP, Hamm HE, Sigler PB (1994) GTPase mechanism of G protein from the 1. 7 Å crystal structure of transducin α·GDP·AlF −4 . Nature (London) 372:276–279

    Article  CAS  Google Scholar 

  59. McLaughlin SK, Mckinnon PJ, Margolskee RF (1992) Gustducin as a taste-cell specific G protein closely related to the transducins. Nature (London) 357:563–569

    Article  CAS  Google Scholar 

  60. Casey PJ, Fong HKW, Simon MI, Gilman AG (1990) Gz, a guanine nucleotide-binding protein with unique biochemical properties. J Biol Chem 265:2383–2390

    CAS  PubMed  Google Scholar 

  61. Kozasa T, Hepler JR, Smrcka AV, Simon MI, Rhee SG, Sternweis PC, Gilman AG (1993) Purification and characterization of recombinant G16α from Sf9 cells: activation of purified phospholipase C isoenzymes by G protein α subunits. Proc Natl Acad Sci USA 90:9176–9180

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Dennis EA, Rhee SG, Billah MM, Hannun YA (1991) Role of phospholipases in generating lipid second messengers in signal transduction. FASEB J 5:2068–2077

    CAS  PubMed  Google Scholar 

  63. Wange RL, Smrcka AV, Sternweis PC, Exton JH (1991) Photoaffinity labeling of two rat liver plasma membrane proteins with [32P]y-azidoanilido GTP in response to vasopressin. J Biol Chem 266:11409–11412

    CAS  PubMed  Google Scholar 

  64. Offermanns S, Laugwitz KL, Spicher K, Schultz G (1994) G proteins of the G12 family are activated via thromboxane A2 and thrombin receptors in human platelets. Proc Natl Acad Sci USA 91:504–508

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Wilkie TM, Scherle PA, Strathmann MP, Slepak VZ, Simon MI (1991) Characterzation of G protein α subunits in the Gq class: expression in murine tissues and in stromal and hematopoietic cell lines. Proc Natl Acad Sci USA 88:10049–10053

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Amatruda TT, Steele DA, Slepak VZ, Simon MI (1991) Gα16, a G protein α subunit specifically expressed in hematopoietic cells. Proc Natl Acad Sci USA 88:5587–5591

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Milligan G, Mullaney I, McCallum JF (1993) Distribution and relative levels of expression of the phosphoinositidase-Clinked G proteins Gqα and G11α:abscence of G11α in human platelets and haematopoietically derived cell lines. Biochim Biophys Acta 1179:208–212

    Article  CAS  PubMed  Google Scholar 

  68. Amatruda TT, Gerard NP, Gerard C, Simon MI (1993) Specific interactions of chemoattractant factor receptors with G proteins. J Biol Chem 268:10139–10144

    CAS  PubMed  Google Scholar 

  69. Wu D, LaRosa GJ, Simon MI (1993) G protein-coupled signal transduction pathways for interleukin-8. Science 261:101–103

    Article  CAS  PubMed  Google Scholar 

  70. Strathmann MP, Simon MI (1991) Goα12 and Gα13 subunits define a fourth class of G protein α subunits. Proc Natl Acad Sci USA 88:5582–5586

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Spicher K, Kalkbrenner F, Zobel A, Harhammer R, Nürnberg B, Söling A, Schultz G (1994) G12 and G13 α-subunits are immunochemically detectable in membranes of most tissues of various mammalian species. Biochem Biophys Res Comm 198:906–914

    Article  CAS  PubMed  Google Scholar 

  72. Harhammer R, Nürnberg B, Spicher K, Schultz G (1994): Purification G protein Gα13 from rat brain membranes. Biochem J 303:135–140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Singer WD, Miller RT, Sternweis PC (1994) Purification and characterization of the α subunit of G13. J Biol Chem 269:19769–19802

    Google Scholar 

  74. Harhammer R, Nürnberg B, Spicher K, Schultz G (1994) Rapid purification of Gα13 from bovine brain membranes: supportive effect of ethylene glycol. Biochem Biophys Res Comm 204:835–840

    Article  CAS  PubMed  Google Scholar 

  75. Harhammer R, Nürnberg B, Spicher K, Schultz G (1995) Differential properties of the purified members of the G protein G12-subfamily. Naunyn Schmiedebergs Arch Pharmacol (in press)

  76. Voyno-Yasenetskaya T, Conklin BR, Gilbert RL, Hooley R, Bourne HR, Barber DL (1994) Gα13 stimulates Na-H exchange. J Biol Chem 269:4721–4724

    CAS  PubMed  Google Scholar 

  77. Dhanasekaran N, Vara Prasad MVVS, Wadsworth SJ, Dermott JM, van Rossum G (1994) protein kinase C-dependent and -independent activation of Na+/H+ exchanger by Gα12 class of G proteins. J Biol Chem 269:11802–11806

    CAS  PubMed  Google Scholar 

  78. Wilk-Blaszczak MA, Singer WD, Gutowski S, Sternweis PC, Berladetti F (1994) The G protein G13 mediates bradykinin inhibition of voltage-dependent calcium current. Neuron 13:1215–1224

    Article  CAS  PubMed  Google Scholar 

  79. Xu N, Bradley L, Ambdukar I, Gutkind JS (1993) A mutant α subunit of G12 potentiates the eicosanoid pathway and is highly oncogenic in NIH 3T3 cells. Proc Natl Acad Sci USA 90:6741–6745

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Jiang H, Wu D, Simon MI (1993) The transforming activity of activated Ga12. FEBS Lett 330:319–322

    Article  CAS  PubMed  Google Scholar 

  81. Xu N, Voyno-Yasenetskaya T, Gutkind JS (1994) Potent transforming activity of the G13 α subunit defines a novel family of oncogenes. Biochem Biophys Res Comm 201:603–609

    Article  CAS  PubMed  Google Scholar 

  82. Chan AML, Fleming TP, McGovern ES, Chedid M, Miki T, Aaronson SA (1993) Expression cDNA cloning of a transforming gene encoding the wild-type Gα12 gene product. Mol Cell Biol 13:762–768

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Yamane HK, Fung BKK (1993) Covalent modifications of G proteins. Annu Rev Pharmacol Toxicol 32:201–241

    Article  Google Scholar 

  84. Casey PJ (1994) Lipid modifications of G proteins. Curr Opin Cell Biol 6:219–225

    Article  CAS  PubMed  Google Scholar 

  85. Casey P (1992) Visual differences. Nature (London) 359:671–672

    Article  CAS  Google Scholar 

  86. Degtyarev MY, Spiegel AM, Jones TL (1993) Increased palmitoylation of the Gs protein α subunit after activation by the β-adrenergic receptor or cholera toxin. J Biol Chem 268:23769–23772

    CAS  PubMed  Google Scholar 

  87. Linder ME, Middleton P, Hepler JR, Taussig R, Gilman AG, Mumby SM (1993) Lipid modifications of G proteins: α subunits are palmitoylated. Proc Natl Acad Sci USA 90:3675–3679

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Parenti M, Vigano MA, Newman CMH, Milligan G, Magee AI (1993) A novel N-terminal motif for palmitoylation of G protein α subunits. Biochem J 291:349–353

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Veit M, Nürnberg B, Spicher K, Harteneck C, Ponimaskin E, Schultz G, Schmidt MFG (1994) The α-subunits of G12 and G13 are palmitoylated, but not amidically myristoylated. FEBS Lett 339:160–164

    Article  CAS  PubMed  Google Scholar 

  90. Mumby SM, Kleuss C, Gilman AG (1994) Receptor regulation of G protein palmtoylation. Proc Natl Acad Sci USA 91:2800–2804

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Wedegaertner PB, Chu DH, Wilson PT, Levis MJ, Bourne HR (1993) Palmitoylation is required for signaling functions and membrane attachment of Gqα and Gsα. J Biol Chem 268:25001–25008

    CAS  PubMed  Google Scholar 

  92. Hallak H, Muszbek L, Laposata M, Belmonte E, Brass LF, Manning DR (1994) Covalent binding of arachidonate to G protein α subunits of human platelets. J Biol Chem 269:4713–4716

    CAS  PubMed  Google Scholar 

  93. Lounsbury KM, Casey PJ, Brass LF, Manning DR (1991) Phosphorylation of Gz in human platelets, selectivity and site of modification. J Biol Chem 266:22051–22056

    CAS  PubMed  Google Scholar 

  94. Lounsbury KM, Schlegel B, Poncz M, Brass LF, Manning DR (1993) Analysis of Gzα by site-directed mutagenesis. J Biol Chem 268:3494–3498

    CAS  PubMed  Google Scholar 

  95. Strassheim D, Malbon CC (1994) Phosphorylation of Gαi2 attenuates inhibitory adenylyl cyclase in neuroblastoma/glioma hybrid (NG-108–15) cells. J Biol Chem 269:14307–14313

    CAS  PubMed  Google Scholar 

  96. Pfeifer A, Nürnberg B, Kamm S, Uhde U, Schultz G, Ruth P, Hofmann F (1995) Cyclic GMP-dependent protein kinase blocks pertussis toxin-sensitive hormone receptor signaling pathways in CHO-cells. J Biol Chem (in press)

  97. Iñiguez-Lluhi J, Kleuss C, Gilman AG (1993) The importance of G protein βγ subunits. Trends Cell Biol 3:230–236

    Article  PubMed  Google Scholar 

  98. Watson AJ, Katz A, Simon MI (1994) A fifth member of the mammalian G protein β-subunit family. J Biol Chem 269:22150–22156

    CAS  PubMed  Google Scholar 

  99. Spring DJ, Neer EJ (1994) A 14-amino acid region of the G protein γ subunit is sufficient to confer selectivity of γ binding to the β subunit. J Biol Chem 269:22882–22886

    CAS  PubMed  Google Scholar 

  100. Kisselev OG, Ermolaeva MV, Gautam N (1994) A farnesylated domain in the G protein γ subunit is a specific determinant of receptor coupling. J Biol Chem 269:21399–21402

    CAS  PubMed  Google Scholar 

  101. Neer EJ, Schmidt CJ, Nambudripad R, Smith TF (1994) The ancient regulatory-protein family of WD-repeat proteins. Nature (London) 371:297–300

    Article  CAS  Google Scholar 

  102. Lupas A, van Dyke M, Stock J (1991) Predicting coiled coils from protein sequences. Science 252:1162–1164

    Article  CAS  PubMed  Google Scholar 

  103. Lupas AN, Lupas JM, Stock JB (1992) Do G protein subunits associate via a three-stranded coiled coil? FEBS Lett 314:105–108

    Article  CAS  PubMed  Google Scholar 

  104. Garritsen A, van Galen PJM, Simonds WF (1993) The Nterminal coiled-coil domain of β is essential for γ association: a model for G protein βγ subunit interaction. Proc Natl Acad Sci USA 90:7706–7710

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Simonds WF, Manji HK, Garritsen A (1993) G proteins and βARK: a new twist for the coiled coil. Trends. J Biochem Sci 18:315–317

    Article  CAS  Google Scholar 

  106. Bubis J, Khorana HG (1990) Sites of interaction in the complex between β- and γ-subunits of transducin. J Biol Chem 265:12995–12999

    CAS  PubMed  Google Scholar 

  107. Pronin AN, Gautam N (1992) Interaction between G protein β and γ subunit types is selective. Proc Natl Acad Sci USA 89:6220–6224

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Higgins JB, Casey PJ (1994) In vitro processing of recombinant G protein γ subunits. J Biol Chem 269:9067–9073

    CAS  PubMed  Google Scholar 

  109. Fukada Y, Matsuda T, Kokame K, Takao T, Shimonishi Y, Akino T, Yoshizawa T (1994) Effects of carboxyl methylation of photoreceptor G protein γ-subunit in visual transduction. J Biol Chem 269:5163–5170

    CAS  PubMed  Google Scholar 

  110. Dietrich A, Meister M, Brazil D, Camps M, Gierschik P (1994) Stimulation of phospholipase C-β2 by recombinant guanine-nucleotide-binding protein βγ-dimers produced in a baculovirus/insect cell expression system. Requirement of γsubunit isoprenylation for stimulation of phospholipase C. Eur J Biochem 219:171–178

    Article  CAS  PubMed  Google Scholar 

  111. Yamada M, Jahangir A, Hosoya Y, Inanobe A, Katada T, Kurachi Y (1994) GK * and brain Gβγ activate muscarinic K+ channel through the same mechanism. J Biol Chem 268:24551–24554

    Google Scholar 

  112. Thomason PA, James SR, Casey PJ, Downes CP (1994) A G protein βγ-subunit-responsive phosphoinositide 3-kinase activity in human platelet cytosol. J Biol Chem 269:16525–16528

    CAS  PubMed  Google Scholar 

  113. Lefkowitz RJ (1993) G protein-coupled receptor kinases. Cell 74:409–412

    Article  CAS  PubMed  Google Scholar 

  114. Crespo P, Xu N, Simonds WF, Gutkind JS (1994) Ras-dependent activation of MAP kinase pathway mediated by G protein βγ subunits. Nature (London) 369:418–420

    Article  CAS  Google Scholar 

  115. Faure M, Voyno-Yasenetskaya TA, Bourne HR (1994) cAMP and βγ subunits of heterotrimeric G proteins stimulate the mitogen-activated protein kinase pathway in COS-7 cells. J Biol Chem 269:7851–7854

    CAS  PubMed  Google Scholar 

  116. Musacchio A, Gibson T, Rice P, Thompson J, Saraste M (1993) The PH domain: a common piece in the structural patchwork of signalling proteins. Trends Biochem Sci 18:343–348

    Article  CAS  PubMed  Google Scholar 

  117. Gibson T, Hyvönen M, Musacchio A, Saraste M, Birney E (1994) PH domain: the first anniversary. Trends Biochem Sci 19:349–353

    Article  CAS  PubMed  Google Scholar 

  118. Parker PJ, Hemmings BA, Gierschik P (1994) PH domains and phospholipases — a meaningful relationship? Trends Biochem Sci 18:343–348

    Google Scholar 

  119. Touhara K, Inglese J, Pitcher JA, Shaw G, Lefkowitz RJ (1994) Binding of G protein βγ-subunits to pleckstrin homology domains. J Biol Chem 269:10217–10220

    CAS  PubMed  Google Scholar 

  120. Ismailov II, McDuffie JH, Benos DJ (1994) Protein kinase A phosphorylation and G protein regulation of purified renal Na+ channels in planar bilayer membranes. J Biol Chem 269:10235–10241

    CAS  PubMed  Google Scholar 

  121. Bubien JK, Jope RS, Warnock DG (1994) G proteins modulate amiloride-sensitive sodium channels. J Biol Chem 269:17780–17783

    CAS  PubMed  Google Scholar 

  122. Bokoch GM, Gilman AG (1984) Inhibition of receptor-mediated release of arachdonic acid by pertussis toxin. Cell 39:301–308

    Article  CAS  PubMed  Google Scholar 

  123. Okajima F, Ui M (1984) ADP-ribosylation of the specific membrane proteins by islet-activating protein, pertussis toxin, associated with inhibition of a chemotactic peptide-induced arachidonate release in neutrophils. J Biol Chem 259:13863–13871

    CAS  PubMed  Google Scholar 

  124. Exton JH (1990) Signaling through phosphatidylcholine breakdown. J Biol Chem 265:1–4

    CAS  PubMed  Google Scholar 

  125. Fasolato C, Innocenti B, Pozzan T (1994) Receptor-activated Ca2+ influx: how many mechanisms for how many channels? Trends Pharmacol. Sci. 15:77–83

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institut für Pharmakologie, Freie Universität Berlin, Thielallee 67-73, D-14195, Berlin, Germany

    B. Nürnberg, T. Gudermann & G. Schultz

Authors
  1. B. Nürnberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. Gudermann
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G. Schultz
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nürnberg, B., Gudermann, T. & Schultz, G. Receptors and G proteins as primary components of transmembrane signal transduction. J Mol Med 73, 123–132 (1995). https://doi.org/10.1007/BF00198240

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00198240

Key words

Search

Navigation