Heterotrimeric G proteins

Current Opinion in Cell Biology

Volumn 8, Issue 2, 1996, Pages 189-196

  Hamm, Heidi E ^a   Gilchrist, Annette ^a  

^a UNIVERSITY OF ILLINOIS AT CHICAGO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DIMER; GUANINE NUCLEOTIDE BINDING PROTEIN; GUANOSINE TRIPHOSPHATE; OLIGOMER; PROTEIN SUBUNIT; RECEPTOR;

CRYSTAL STRUCTURE; HYDROLYSIS; NUCLEOTIDE METABOLISM; PRIORITY JOURNAL; PROTEIN CONFORMATION; PROTEIN LIPID INTERACTION; PROTEIN MODIFICATION; PROTEIN PROTEIN INTERACTION; PROTEIN QUATERNARY STRUCTURE; RECEPTOR BINDING; REVIEW; SIGNAL TRANSDUCTION; X RAY CRYSTALLOGRAPHY;

EID: 0029875554     PISSN: 09550674     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0955-0674(96)80065-2     Document Type: Article

References (108)

1. Emala CW, Schwindinger WF, Wand GS, Levine MA: Signal-transducing G proteins: basic and clinical implications. Prog Nucleic Acid Res Mol Biol 1994, 47:81-111.
2. Neer EJ: Heterotrimeric G proteins: organizers of transmembrane signals. Cell 1995, 80:249-257.
3. KACh.
4. Helms JB: Role of heterotrimeric GTP binding proteins in vesicular protein transport: indications for both classical and alternative G protein cycles. FEBS Lett 1995, 369:84-88.
5. Neer EJ: G proteins: critical control points for transmembrane signals. Protein Sci 1994, 3:3-14.
6. Ueda N, Iniguez-Lluhi JA, Lee E, Smrcka AV, Robishaw JD, Gilman AG: G protein βγ subunits. J Biol Chem 1994, 269:4388-4395.
7. Pronin AN, Gautam N: Interaction between G-protein β and γ subunit types is selective. Proc Natl Acad Sci USA 1992, 89:6220-6224.
8. Watson AJ, Katz A, Simon MI: A fifth member of the mammalian G-protein β-subunit family. Expression in brain and activation of the β2 isotype of phospholipase C. J Biol Chem 1994, 269:22150-22156.
9. Wilcox MD, Schey KL, Busman M, Hildebrandt JD: Determination of the complete covalent structure of the γ2 subunit of bovine brain γ proteins by mass spectrometry. Biochem Biophys Res Commun 1995, 212:367-374. Both the Gα and Gγ subunit composition define the makeup of the heterotrimeric G protein.
10. Ray K, Kunsch C, Bonner LM, Robishaw JD: Isolation of cDNA clones encoding eight different human G protein γ subunits, including three novel forms designated the γ4, γ10, and γ11 subunits. J Biol Chem 1995, 270:21765-21771. The expressed sequence tag method was used to isolate five γ subunit homologs, in addition to three novel subunits, from a human cDNA database.
11. Lee C, Murakami T, Simonds WF: Identification of a discrete region of the G protein γ subunit conferring selectivity in βγ complex formation. J Biol Chem 1995, 270:8779-8784. The authors dimerized different Gβ and Gγ subunits, and then mapped the region responsible for Gβ2 dimerization to Gγ2 using γ1-γ2 chimeras.
12. Sondek J, Bohm A, Lambright DG, Hamm HE, Sigler PB: The 2.1 Å crystal structure of a G protein βγ dimer. Nature 1996, 379:369-374. The authors report the high resolution crystal structure of the Gβγ dimer of Gt. The structural details of the interactions between Gβ and Gγ subunits are noted, including those implicated in effector modulation.
13. Lambright DG, Sondek J, Bohm A, Skiba NK, Hamm HE, Sigler PB: The 2.0 Å crystal structure of a heterotrimeric G protein. Nature 1996, 370:413-424. The authors report the high resolution crystal structure of the heterotrimeric G protein Gt. The interaction between the Gtα and Gtβγ subunits involves two extensive interfaces, one of which is sensitive to GTP binding, which results in subunit dissociation. The sites of post-translational modification of Gtα and Gtγ, in addition to the receptor-binding regions of Gtα, occur on a common face that allows orientation of the heterotrimer with respect to the membrane surface.
14. Ryba NJP, Tirindelli R: A novel GTP-binding protein γ-subunit, Gγ6, is expressed during neurogenesis in the olfactory and vomeronasal neuroepithelia. J Biol Chem 1995, 270:6757-6767.
15. Andreopoulos S, Li PP, Warsh JJ: Developmental expression of Gαo and Gαs isoforms in PC12 cells: relationship to neurite outgrowth. Dev Brain Res 1995, 88:30-36.
16. Knol JC, Ramnatsingh S, Van Kesteren ER, Minnen JV, Planta RJ, Van Heerikhuizen H, Vreugdenhil E: Cloning of a molluscan G protein α subunit of the Gq class which is expressed differentially in identified neurons. Eur J Biochem 1995, 230:193-199.
17. Sato M, Kataoka R, Dingus J, Wilcox M, Hildebrandt JD, Lanier SM: Factors determining specificity of signal transduction by G-protein-coupled receptors. J Biol Chem 1995, 270:15269-15276.
18. Maier O, Ehmsen E, Westermann P: Trimeric G protein α subunits of the Gs and Gi families localized at the golgi membrane. Biochem Biophys Res Commun 1995, 208:135-143.
19. Kehlenbach RH, Matthey J, Huttner WB: XLαs is a new type of G protein. Nature 1994, 372:804-809. A new 'extra large' G protein (with a molecular weight of 92 kDa) was cloned and found to be present in selective populations of endocrine cells and neurons, specifically associated with the trans-Golgi network. The protein is composed of two regions, the amino-terminal XL region (of 498 amino acids), and a carboxy-terminal region (of 348 amino acids) which is identical to amino acids 47-394 of Gαs. The authors suggest XLαs is a product of the single copy Gαs gene with an alternative start site.
20. Neubig RR, Connolly MP, Remmers AE: Rapid kinetics of G protein subunit association: a rate-limiting conformational change? FEBS Left 1994, 355:251-253.
21. Rens-Domiano S, Hamm HE: Structural and functional relationship of heterotrimeric G-proteins. FASEB J 1995 9:1059-1066.
22. Wedegaertner PB, Wilson PT, Bourne HR: Lipid modifications of trimeric G proteins. J Biol Chem 1995, 270:503-506. A minireview that addresses recent advances in understanding how fatty acylation regulates the cellular localization and function of G proteins. The functions and dynamics of myristoylation and palmitoylation of Gα, in addition to the prenylation of Gγ subunits, are discussed.
23. McCallum JF, Wise A, Grassie MA, Magee AI, Guzzi F, Parenti M, Milligan G: The role of palmitoylation of the guanine nucleotide binding protein G11α in defining interaction with the plasma membrane. Biochem J 1995, 310:1021-1027.
24. Degtyarev MY, Spiegel AM, Jones TLZ: Palmitoylation of a G protein αi subunit requires membrane localization not myristoylation. J Biol Chem 1994, 269:30898-30903.
25. Bigay J, Faurobert E, Franco M, Chabre M: Roles of lipid modifications of transducin subunits in their GDP-dependent association and membrane binding. Biochemistry 1994, 33:14081-14090. The authors studied the dependence of the association of Gαt-Gβγt on both the lipid modifications of the subunits and the lipidic environments in which the subunits are found, and conclude that the lipids play a role in cooperative membrane interaction rather than direct protein-protein interaction.
26. Grassie MA, McCallum JF, Guzzi F, Magee AI, Milligan G, Parenti M: The palmitoylation status of the G-protein Go1α regulates its avidity of interaction with the plasma membrane. Biochem J 1994, 302:913-920.
27. Migeon JC, Thomas SL, Nathanson NM: Regulation of cAMP-mediated gene transcription by wild type and mutated G-protein α subunits. J Biol Chem 1994, 269:29146-29152.
28. Milligan G, Parenti M, Magee AI: The dynamic role of palmitoylation in signal transduction. Trends Biochem Sci 1995, 20:181-186. A thorough review of the regulation and functional significance of G-protein palmitoylation.
29. Justice JM, Bliziotes MM, Stevens LA, Moss J, Vaughan M: Involvement of N-myristoylation in monoclonal antibody recognition on chimeric G protein α subunits. J Biol Chem 1995, 270:6436-6439.
30. Src as Tyr37 and Tyr377.
31. Fields TA, Casey, PJ: Phosphorylation of Gzα by protein kinase C blocks interaction with the βγ complex. J Biol Chem 1995, 270:23119-23125.
32. Noel JP, Hamm HE, Sigler PB: The 2.2 Å crystal structure of transducin-α complexed with GTPγS. Nature 1993, 366:654-663.
33. Lambright DG, Noel JP, Hamm HE, Sigler PB: Structural determinants for activation of the α-subunit of a heterotrimeric G protein. Nature 1994, 369:621-628.
34. 4- activates Gα·GDP by binding to the Gα subunit with a geometry resembling that of a pentavaleni intermediate for GTP hydrolysis.
35. Coleman DE, Berghuis AM, Lee E, Linder ME, Gilman AG, Sprang SR: Structures of active conformations of Giα1 and the mechanism of GTP hydrolysis. Science 1994, 269:1405-1412. The three-dimensional structures of the active forms of Gαi are determined by X-ray crystallography. The fold of Gαi differs from that reported for Gαt only in the conformation of a helix-loop sequence located in the α-helical domain of Gαi, and it is suggested that this site may participate in effector binding.
36. Mixon MB, Lee E, Coleman DE, Berghuis AM, Gilman AG, Sprang SR: Tertiary and quaternary structural changes in Giα1 induced by GTP hydrolysis. Science 1995, 270:954-960.
37. Skiba NP, Bae H, Hamm HE: Mapping of effector binding sites of transducin α-subunit using Gαt/Gαi1 chimeras. J Biol Chem 1996, 271:413-424.
38. Codina J, Birbanumer L: Requirement for intramolecular domain interaction in activation of G protein α subunit by aluminum fluoride and GDP but not by GTPγS. J Biol Chem 1994, 269:29339-29342.
39. Markby DW, Onrust R, Bourne HR: Separate GTP binding and GTPase activating domains of a Gα subunit Science 1993, 262:1895-1901.
40. Bourne HR: Trimeric G proteins: surprise witness tells a tale. Science 1995, 270:933-934.
41. Schweins T, Geyer M, Scheffzek K, Warshel A, Kalbitzer HR, Wittinghofer A: Substrate-assisted catalysis as a mechanism for GTP hydrolysis of p21Ras. Nature Struct Biol 1995, 2:36-44.
42. Hilgenfeld R: Regulatory GTPases. Curr Opin Struct Biol 1995, 5:810-817.
43. Landis CA, Masters SB, Spads A, Pace AM, Bourne HR, Valler L: GTPase inhibiting mutations activate the alpha chain of Gs and stimulate adenylyl cyclase in human pituitary tumors. Nature 1989, 340:692-696.
44. Neer EJ: The ancient regulatory-protein family of WD repeat proteins. Nature 1995, 300:297-300.
45. Wall MA, Coleman DE, Lee E, Iniguez-Lluhl JA, Posner BA, Gilman AG, Sprang SR: The structure of the G protein heterotrimer Giα1β1γ2. Cell 1995, 83:1047-1058. The crystallographic structure of a G protein heterotrimer complex composed of Gαi1 ,Gβ1 ,and Gγ2 subunits is presented.
46. Casey PJ: Protein lipidation in cell signaling. Science 1995, 268:221-225.
47. Kalman VK, Erdman RA, Maltese WA Robishaw JD: Regions outside of the CAAX motif influence the specificity of prenylation of G protein γ subunits. J Biol Chem 1995, 270:14835-14841. The structural requirements for attachment of prenyl groups to various Gγ subunits were studied. Gγ2 was modified by a C20 geranylgeranyl group, whereas Gγ1 and a mutant Gγ2 (a Ser71 mutant) were modified by both C15 farnesyl and C20 geranylgeranyl groups.
48. Higgins JB, Casey PJ: In vitro processing of recombinant G protein γ subunits. J Biol Chem 1994, 269:9067-9073.
49. Scheer A, Gierschik P: S-Prenylated cysteine analogues inhibit receptor-mediated G protein activation in native human granulocyte and reconstituted bovine retinal rod outer segment membranes. Biochemistry 1995, 34:4952-4961.
50. Garritsen A, Simonds WF: Multiple domains of G protein β confer subunit specificity in βγ interaction. J Biol Chem 1994, 269:24418-24423. The authors utilize a chimeric approach and transient transfections to examine selectivity of Gβγ heterodimer formation.
51. Katz A, Simon MI: A segment of the C-terminal half of the G-protein β1 subunit specifies its interaction with the γ1 subunit Proc Natl Acad Sci USA 1995, 92:1998-2002. Gβ1-β2 chimeras were used to identify the regions in β1 that determine its association with γ1. A chimera between β2 and β1 that comprises the carboxy-terminal 173 amino acid residues of β1 can interact with and activate phosphatidylinositol-phospholipase C-β2 when γ1 is coexpressed.
52. Yamauchi J, Kaziro Y, Itoh H: Carboxyl terminal of G protein β subunit is required for association with γ subunit. Biochem Biophys Res Commun 1995, 214:694-700. The last ten amino acid residues within the seventh WD-repeating unit of Gβ1 were found to be essential for Gγ1 association, while the same region within Gβ2 is needed for interaction with Gγ2.
53. Spring DJ, Neer EJ: 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 1994, 269:22882-22886. A series of γ1-γ2 chimeras were used to determine that when amino acids 36-49 of Gγ1 are substituted for amino acids 33-46 of Gγ2, the chimera behaves like Gγ1, and only dimerizes with β1. The reciprocal chimeras behaved like Gγ2 and interact with both β1 and β2 when assayed by trypsin protection and chemical cross-linking.
54. Garritsen A, Galen PJMV, Simonds WF: The N-terminal coiled-coil domain of βis essential for γ association: a model for G-protein βγ subunit interaction. Proc Natl Acad Sci USA 1993, 90:7706-7710.
55. Slepak VZ, Wilkie TM, Simon MI: Mutational analysis of G protein a subunit Goα expressed in Escherichia coli. J Biol Chem 1993, 268:1414-1423.
56. Hargrave PA, Hamm HE, Hofmann KP: Interaction of rhodopsin with the G-protein, transducin. Bioessays 1993 15:43-50.
57. Phillips WJ, Cerione RA: Rhodopsin-transducin interactions. I. Characterization of the binding of the transducin-βγ subunit complex to rhodopsin using fluorescence spectroscopy. J Biol Chem 1992, 267:17032-17039.
58. Kisselev OG, Ermolaeva MV, Gautam N: A farnesylated domain in the G protein γ subunit is a specific determinant of receptor coupling. J Biol Chem 1994, 269:21399-21402. The authors provide evidence that a chemically farnesylated peptide, which is specific to the carboxy-terminal domain of the Gtγ subunit (amino acids 60-71), directly stabilizes the active form of rhodopsin, metarhodopsin II, and uncouples the rhodopsin-Gt interaction.
59. Martin EL, Rens-Domiano S, Schatz PJ, Hamm HE: Potent peptide analogues of a G-protein receptor binding region obtained with a combinatorial library. J Biol Chem 1996, 271:361-366. Using a combinatorial peptide library based on the carboxyl terminus of the a subunit of Gt, peptides which bind rhodopsin with greater than 100-fold higher affinity than the native sequence were identified.
60. Rasenick MM, Watanabe M, Lazarevic MB, Hatta G, Hamm HE: Synthetic peptides as probes for G protein function. Carboxyl-terminal G-alpha(s) peptides mimic G(s) and evoke high affinity agonist binding to the beta-adrenergic receptors. J Biol Chem 1994, 269:21519-21525.
61. Hamm HE, Deretic D, Arendt A, Hargrave PA, Koenig B, Hoffmann KP: Site of G protein binding to rhodopsin mapped with synthetic peptides from the α subunit. Science 1988, 241:832-835.
62. Schertler GF, Villa C, Henderson R: Projection structure of rhodopsin. Nature 1993, 362:770-772.
63. Taylor JM, Jacob-Mosier GG, Lawton RG, Remmers AE, Neubig RR: Binding of an α2 adrenergic receptor third intracellular loop peptlde to Gβ and the amino terminus of Gα. J Biol Sci 1994, 269:27618-27624.
64. Denker BM, Boutin PM, Neer EJ: Interactions between the amino- and carboxyl-terminal regions of Gα subunits: analysis of mutated Gαo/Gαi2 chimeras. Biochemistry 1995, 34:5544-5553. Three Hydrophobic amino acids near the carboxyl terminus of Gα were found to be important for inducing the conformational change that allows decreased GDP affinity, and subsequent activation of Gα, to occur. The authors suggest that the disruption of contacts with the amino-terminal β1 and β3 strands is the major contributor to the final phenotype (which is a reduced affinity for GDP as compared with the native G protein).
65. Slepak VZ, Katz A, Simon MI: Functional analysis of a dominant negative mutant of Gαi2. J Biol Chem 1995, 270:4037-4041.
66. Rarick HM, Artemyev NO, Hamm HE: A site on rod G protein α subunit that mediates effector activation. Science 1992, 256:1031-1033.
67. Spickofsky N, Robichon A, Danho W, Fry D, Greeley D, Graves B, Madison V, Margolskee RF: Biochemical analysis of the transducin-phosphodiesterase interaction. Nature Struct Biol 1994, 1:771-781.
68. Popova JS, Johnson GL, Rasenick MM: Chimeric Gαs/Gαi2 proteins define domains on Gαs that interact with tubulin for β-adrenergic activation of adenylyl cyclase. J Biol Sci 1994, 269:21748-21754.
69. Clapham DE, Neer EJ: New roles for G-protein βγ-dimers in transmembrane signalling. Nature 1993, 365:403-406.
70. Whiteway MS, Wu C, Leeuw T, Clark K, Fourest-Lieuvin A, Thomas DY, Leberer E: Association of the yeast pheromone response G protein βγ subunits with the MAP kinase scaffold Ste5p. Science 1995, 269:1572-1575. A haploid-specific interaction between the amino terminus of the MAPK scaffold protein Ste5p and the Gβ subunit Ste4p was detected using a yeast two-hybrid assay. In addition, the authors show that in cells with a constitutively activated pheromone-response pathway, epitope-tagged Ste4p coimmunoprecepitates with Ste5p.
71. Reuveny E, Siesinger PA, Inglese J, Morales JM, Iniguez-Lluhi JA, Lefkowitz RJ, Bourne HR, Jan YN, Jan LY: Activation of the cloned muscarinic potassium channel by G protein βγ subunits. Nature 1994, 370:143-146.
72. + channel (GIRK) 2, but not GIRK3, can be directly activated on coexpression of G-protein subunits Gβ1 and Gγ2 in Xenopus oocytes. Coinjection of GIRK1 with GIRK2 or GIRK3 cRNA was found to give a much larger G protein induced current than either cRNA expressed individually. Coinjection of GIRK2 and GIRK3 mRNA suppressed the G-protein response of GIRK2.
73. + channel 1 (nucleotides 538-1503) binds to purified Gβγ, and this interaction can be specifically inhibited by Gα·GTPγS but not by Gα·GDP.
74. Slesinger PA, Reuveny E, Jan YN, Jan LY: Identification of structural elements involved in G protein gating of the GIRK1 potassium channel. Neuron 1995, 15:1145-1156.
75. + channel.
76. Camps M, Carozzi A, Schnabel P, Scheer A, Parker PJ, Gierschik P: Isozyme-selective stimulation of phospholipase C-β2 by G protein βγ-subunits. Nature 1992, 360:684-686.
77. Smrcka AV, Sternweis PC: Regulation of purified subtypes of phosphatidylinositol-specific phospholipase C β by G protein α and βγ subunits. J Biol Chem 1993, 268:9667-9674.
78. Murthy KS, Makhiouf GM: Adenosine A1 receptor-mediated activation of phospholipase C-β3 in intestinal muscle: dual requirement for α and βγ subunits of Gi3. Mol Pharmacol 1995, 47:1172-1179.
79. ++ release in Xenopus oocytes. J Biol Chem 1995, 270:30068-30074.
80. Taussig R, Quarmby LM, Gilman AG: Regulation of purified type I and type II adenylyl cyclases by G protein βγ subunits. J Biol Chem 1993, 269:9-12.
81. Chen J, DeVivo M, Dingus J, Harry A, Li J, Sui J, Carty DJ, Blank JL, Exton JH, Stoffel RH et al.: A region of adenylyl cyclase 2 critical for regulation by G protein βγ subunits. Science 1995, 268:1166-1169.
82. Jelsema CL, Axelrod J: Stimulation of phospholipase A2 activity in bovine rod outer segments by the βγ subunit of transducin and its inhibition by the α subunit. Proc Natl Acad Sci USA 1987, 84:3623-3627.
83. +-channel via phospholipase A2. Nature 1989, 337:557-560.
84. Morris AJ, Rudge SA, Mahlum CE, Jenco JM: Regulation of phosphoinositide-3-kinase by G protein βγ subunits in a rat osteosarcoma cell line. Mol Pharmacol 1995, 48:532-539.
85. Zhang J, Zhang J, Benovic JL, Sugai M, Wetzker R, Gout I, Rittenhouse SE: Sequestration of a G-protein βγ subunit or ADP-ribosylation of Rho can inhibit thrombin-induced activation of platelet phosphoinositide 3-kinases. J Biol Chem 1995, 270:6589-6594.
86. Tsukada S, Simon MI, White ON, Katz A: Binding of βγ subunits of heterotrimeric G proteins to the PH domain of Bruton tyrosine kinase. Proc Natl Acad Sci USA 1994, 91:11256-11260.
87. Langhans-Rajasekaran SA, Wan Y, Huang X-Y: Activation of Tsk and Btk tyrosine kinases by G protein βγ subunits. Proc Natl Acad Sci USA 1995, 92:8601-8605.
88. 2+-induced regulation of ion channel and MAPK functions. Nature 1995, 376:737-745. Reports the cloning of a novel tyrosine kinase, PYK2, which is highly expressed in the central nervous system of rats, and which is rapidly phosphorylated in response to signals that result in elevated levels of cytosolic calcium influx. The authors suggest that PYK2 may link G protein coupled receptors to the MAPK cascade.
89. Faure M, Voyno-Yasenetskaya TA, Bourne HR: cAMP and βγ subunits of heterotrimeric G proteins stimulate the mitogen-activated protein kinase pathway in COS-7 cells. J Biol Chem 1994, 269:7851-7854.
90. Ito A, Satoh T, Kaziro Y, Itoh H: G protein βγ subunit activates Ras, Raf, and MAP kinase in HEK 294 cells. FEBS Lett 1995, 368:183-187.
91. Vara Prasad MVVS, Dermott JM, Heasley LE, Johnson GL, Dhanasekaran N: Activation of Jun kinase/stress-activated protein kinase by GTPase-deficient mutants of Gα12 and Gα13. J Biol Chem 1995, 270:18655-18659. Constitutively active forms of Gα12 or Gα13 cause increased Jun kinase/stress-activated protein kinase activity in NIH3T3 cells through Ras activation.
92. Touhara K, Hawes BE, Van Biesen T, Lefkowitz RJ: G protein βγ subunits stimulate phosphorylation of Shc adapter protein. Proc Natl Acad Sci USA 1995, 92:9284-9287.
93. Van Biesen T, Hawes BE, Luttrell DK, Krueger KM, Touhara K, Porfiri E, Sakaue M, Luttrell LM, Lefkowitz RJ: Receptor-tyrosine kinase- and Gβγ-mediated MAP kinase activation by a common signalling pathway. Nature 1995, 376:781-784.
94. Pitcher JA, Inglese J, Higgins JB, Arriza JL, Casey JP, Kim C, Benovic JL, Kwatra MM, Caron MG, Lefkowitz RJ: Role of βγ subunits of G proteins in targeting the β adrenergic receptor kinase to membrane-bound receptors. Science 1992, 257:1264-1267.
95. Pumiglia KM, LeVine H, Haske T, Habib T, Jove R, Decker SJ: A direct interaction between G-protein βγ subunits and the Raf-1 protein kinase. J Biol Chem 1995, 270:14251-14254. Using the yeast two-hybrid system, the authors identified a clone encoding the carboxy-terminal half of Gβ2 that interacts with the amino terminus (amino acids 136-239) of Raf-1. In addition, Raf-1 co-immunoprecipitated with Gβγ in 293-T cells.
96. GDP binds to the Gtβγ subunit of transducin but not to GtαGDP-Gtβγ. FEBS Lett 1995, 362:286-290.
97. Colombo MI, Inglese J, D'Souza-Schorey C, Beroni W, Stahl PD: Heterotrimeric G proteins interact with the small GTPase ARF. J Biol Chem 1995, 270:24564-24571.
98. Haga K, Kameyama K, Haga T: Synergistic activation of a G-protein-coupled receptor kinase by G-protein βγ subunits and mastoparan or related peptides. J Biol Chem 1994, 269:12594-12599.
99. Koch WJ, Inglese J, Stone WC, Lefkowitz RJ: The binding site for the βγ subunits of heterotrimeric G-proteins on the β-adrenergic receptor kinase. J Biol Chem 1993, 268:8256-8260.
100. Leberer E, Dignard D, Hougan L, Thomas DY, Whiteway M: Dominant-negative mutants of a yeast G-protein β subunit identify two functional regions involved in pheromone signalling. EMBO J 1992, 11:4805-4813.
101. Grishin AV, Weiner JL, Blumer KJ: Biochemical and genetic analysis of dominant-negative mutations affecting a yeast G-protein γ subunit. Mol Cell Biol 1994, 14:4571-4578.
102. Whiteway M, Clark KL, Leberer E, Dignard D, Thomas DY: Genetic identification of residues involved in association of α and β G-protein subunits. Mol Cell Biol 1994, 14:3223-3229.
103. Dharmawardhane S, Cubitt AB, Clark AM, Firtel RA: Regulatory role of the Gα1 subunit in controlling cellular morphogenesis in Dictyostelium. Development 1994, 120:3549-3561. The role of Gα1 (one of eight Dictyostelium α subunits) during multicellular development is defined by its deletion, overexpression, and constitutive activation. The authors suggest that Gα1 exerts its signal during early development by altering the guanyl cyclase pathway.
104. Gao P, Watkins DC, Malbon CC: Constitutively active mutant Gsα (G225T) and null-mutant Gαi2 (G203T) induce primitive endoderm from stem cells. Am J Physiol 1995, 268:1460-1466. Expression of either a constitutively active Gαs mutant (G225T) or a null mutant of Gαi2 (G203T) induces stem cells to differentiate into primitive endoderm.
105. Heasley LE, Zamarripa J, Storey B, Helfrich B, Mitchell FM, Bunn PA Jr, Johnson GL: Discordant signal transduction and growth inhibition of small cell lung carcinomas induced by expression of GTPase-deficient Gα16. J Biol Chem 1996, 271:349-354.
106. Schnabel P, Bohm M: Mutations of signal-transducing G proteins in human disease. J Mol Med 1995, 73:221-228.
107. Michiels F-M, Caillou B, Talbot M, Dessarps-Freichey F, Maunoury M-T, Schlumberger M, Mercken L, Monier R, Feunteun J: Oncogenic potential of guanine nucleotide stimulatory factor αsubunit In thyroid glands of transgenic mice. Proc Natl Acad Sci USA 1994, 91:10488-10492. The authors generated transgenic mice expressing a mutant Gαs subunit gene (gsp) under the control of bovine thyroglobulin promoter. The animals developed hyperfunctioning thyroid adenomas.
108. -/- mice) showed growth retardation, thymocyte abnormalities, and a progressive, severe and ultimately lethal form of ulcerative colitis.