Insights into G Protein Structure, Function, and Regulation

Endocrine Reviews

Volumn 24, Issue 6, 2003, Pages 765-781

  Cabrera Vera, Theresa M ^a   Vanhauwe, Jurgen ^a   Thomas, Tarita O ^a   Medkova, Martina ^a   Preininger, Anita ^a   Mazzoni, Maria R ^b,c   Hamm, Heidi E ^a,b  

^a NORTHWESTERN UNIVERSITY   (United States)

^b VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c UNIVERSITY OF PISA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

CHEMOKINE; GUANINE NUCLEOTIDE BINDING PROTEIN; NEUROTRANSMITTER; PROTEIN SUBUNIT; REGULATOR PROTEIN;

CAENORHABDITIS ELEGANS; HOMEOSTASIS; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN DOMAIN; PROTEIN FUNCTION; PROTEIN STRUCTURE; REVIEW; SIGNAL TRANSDUCTION;

ANIMALS; GTP-BINDING PROTEINS; HUMANS; LIPID METABOLISM; MOLECULAR STRUCTURE; PHOSPHORYLATION; PROTEINS; RECEPTORS, CELL SURFACE; SIGNAL TRANSDUCTION; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0347949548     PISSN: 0163769X     EISSN: None     Source Type: Journal    
DOI: 10.1210/er.2000-0026     Document Type: Review

References (241)

1. Hamm HE 1998 The many faces of G protein signaling. J Biol Chem 273:669-672
2. Sprang SR 1997 G protein mechanisms: insights from structural analysis. Annu Rev Biochem 66:639-678
3. Noel JP, Hamm HE, Sigler PB 1993 The 2. 2 Å crystal structure of transducin-α complexed with GTPγS. Nature 366:654-663
4. Lambright DG, Noel JP, Hamm HE, Sigler PB 1994 Structural determinants for activation of the α-subunit of a heterotrimeric G protein. Nature 369:621-628
5. -. Nature 372:276-279
6. Coleman DE, Berghuis AM, Lee E, Linder ME, Gilman AG, Sprang SR 1994 Structures of active conformations of Giα1 and the mechanism of GTP hydrolysis. Science 265:1405-1412
7. Lambright DG, Sondek J, Bohm A, Skiba NP, Hamm HE, Sigler PB 1996 The 2. 0 Å crystal structure of a heterotrimeric G protein. Nature 379:311-319
8. Wall MA, Coleman DE, Lee E, Iniguez-Lluhi JA, Posner BA, Gilman AG, Sprang SR 1995 The structure of the G protein heterotrimer Giα1β 1γ2. Cell 83:1047-1058
9. Rens-Domiano S, Hamm HE 1995 Structural and functional relationship of heterotrimeric G-proteins. FASEB J 9:1059-1066
10. Downes GB, Gautam N 1999 The G protein subunit gene families. Genomics 62:544-552
11. Denker BM, Boutin PM, Neer EJ 1995 Interactions between the amino-and carboxyl-terminal regions of Gα subunits: analysis of mutated Gαo/Gα i2 chimeras. Biochemistry 34:5544-5553
12. 2+ on the GTPase activity and the fluorescent properties of Go. J Biol Chem 26:757-761
13. Stryer L 1986 Cyclic GMP cascade of vision. Annu Rev Neurosci 9:87-119
14. Iiri T, Herzmark P, Nakamoto JM, van Dop C, Bourne HR 1994 Rapid GDP release from Gsα in patients with gain and loss of endocrine function. Nature 371:164-168
15. Posner BA, Mixon MB, Wall MA, Sprang SR, Gilman AG 1998 The A326S mutant of Giα1 as an approximation of the receptor-bound state. J Biol Chem 273:21752-21758
16. Thomas TC, Schmidt CJ, Neer EJ 1993 G-protein αo subunit: mutation of conserved cysteines identifies a subunit contact surface and alters GDP affinity. Proc Natl Acad Sci USA 90:10295-10298
17. Marin EP, Krishna AG, Sakmar TP 2001 Rapid activation of transducin by mutations distant from the nucleotide-binding site: evidence for a mechanistic model of receptor-catalyzed nucleotide exchange by G proteins. J Biol Chem 276:27400-27405
18. Echeverria V, Hinrichs MV, Torrejon M, Ropero S, Martinez J, Toro MJ, Olate J 2000 Mutagenesis in the switch IV of the helical domain of the human Gsα reduces its GDP/GTP exchange rate. J Cell Biochem 76:368-375
19. Remmers AE, Engel C, Liu M, Neubig RR 1999 Interdomain interactions regulate GDP release from heterotrimeric G proteins. Biochemistry 38:13795-13800
20. Grishina G, Berlot CH 1998 Mutations at the domain interface of Gsα impair receptor-mediated activation by altering receptor and guanine nucleotide binding. J Biol Chem 273:15053-15060
21. Yang C-S, Skiba NP, Mazzoni MR, Hamm HE 1999 Conformational changes at the carboxyl terminus of Gα occur during G protein activation. J Biol Chem 274:2379-2385
22. Muradov KG, Artemyev NO 2000 Coupling between the N- and C-terminal domains influences transducin-α intrinsic GDP/GTP exchange. Biochemistry 39:3937-3942
23. Bourne HR 1997 How receptors talk to trimeric G proteins. Curr Opin Cell Biol 9:134-142
24. Bohm A, Gaudet R, Sigler PB 1997 Structural aspects of heterotrimeric G-protein signaling. Curr Opin Biotechnol 8:480-487
25. Iiri T, Farfel Z, Bourne HR 1998 G-protein diseases furnish a model for the turn-on switch. Nature 394:35-38
26. Ford CE, Skiba NP, Bae H, Daaka Y, Reuveny E, Shekter LR, Rosal R, Weng G, Yang C-S, Iyengar R, Miller RJ, Jan LY, Lefkowitz RJ, Hamm HE 1998 Molecular basis for interactions of G protein βγ subunits with effectors. Science 280:1271-1274
27. Schoneberg T, Schultz G, Gudermann T 1999 Structural basis of G protein-coupled receptor function. Mol Cell Endocrinol 151:181-193
28. LeVine III H 1999 Structural features of heterotrimeric G-protein-coupled receptors and their modulatory proteins. Mol Neurobiol 19:111-149
29. Wess J 1997 G-protein-coupled receptors: molecular mechanisms involved in receptor activation and selectivity of G-protein recognition. FASEB J 11:346-354
30. Conklin BR, Bourne HR 1993 Structural elements of Gα subunits that interact with Gβγ, receptors, and effectors. Cell 73:631-641
31. Martin EL, Rens-Domiano S, Schatz PJ, Hamm HE 1996 Potent peptide analogues of a G protein receptor-binding region obtained with a combinatorial library. J Biol Chem 271:361-366
32. Van Dop C, Yamanaka G, Steinberg F, Sekura RD, Manclark CR, Stryer L, Bourne H 1984 ADP-ribosylation of transducin by pertussis toxin blocks the light-stimulated hydrolysis of GTP and cGMP in retinal photoreceptors. J Biol Chem 259:23-26
33. Unemori H, Inoue T, Kume S, Sekiyama N, Nagao M, Itoh H, Nakanishi S, Mikoshiba K, Yamamoto T 1997 Activation of G protein Gq/11 through tyrosine phosphorylation of the α subunit. Science 276:1878-1881
34. Barr AJ, Brass LF, Manning DR 1997 Reconstitution of receptors and GTP-binding regulatory proteins (G proteins) in Sf9 cells. A direct evaluation of selectivity in receptor G protein coupling. J Biol Chem 272:2223-2229
35. Berstein G, Blank JL, Smrcka AV, Higashijima T, Sternweis PC, Exton JH, Ross EM 1992 Reconstitution of agonist-stimulated phosphatidylinositol 4,5-bisphosphate hydrolysis using purified m1 muscarinic receptor, Gq/11, and phospholipase C-β1. J Biol Chem 267:8081-8088
36. Blahos 2nd J, Mary S, Perroy J, de Colle C, Brabet I, Bockaert J, Pin JP 1998 Extreme C terminus of G protein α-subunits contains a site that discriminates between Gi-coupled metabotropic glutamate receptors. J Biol Chem 273:25765-25769
37. Kostenis E, Gomeza J, Lerche C, Wess J 1997 Genetic analysis of receptor-Gαq coupling selectivity. J Biol Chem 272:23675-23681
38. Conklin BR, Herzmark P, Ishida S, Voyno-Yasenetskaya TA, Sun Y, Farfel Z, Bourne HR 1996 Carboxyl-terminal mutations of Gqα and Gsα that alter the fidelity of receptor activation. Mol Pharmacol 50:885-890
39. McFadzean I, Mullaney I, Brown DA, Milligan G 1989 Antibodies to the GTP binding protein, Go, antagonize noradrenaline-induced calcium current inhibition in NG108-15 hybrid cells. Neuron 3:177-182
40. Hamm HE, Deretic D, Arendt A, Hargrave PA, Koenig B, Hofmann KP 1988 Site of G protein binding to rhodopsin mapped with synthetic peptides from the a subunit. Science 241:832-835
41. Dratz ED, Fursteneau JE, Lambert CG, Thireault DL, Rarick H, Schepers T, Pakhlevaniants S, Hamm HE 1993 NMR structure of a receptor-bound G-protein peptide. Nature 363:276-280
42. Rasenick MM, Watanabe M, Lazarevic MB, Hatta S, Hamm HE 1994 Synthetic peptides as probes for G protein function. Carboxyl-terminal Gαs peptides mimic Gs and evoke high affinity agonist binding to β-adrenergic receptors. J Biol Chem 269:21519-21525
43. Gilchrist A, Mazzoni MR, Dineen B, Dice A, Linden J, Proctor WR, Lupica CR, Dunwiddie TV, Hamm HE 1998 Antagonists of the receptor-G protein interface block Gi-coupled signal transduction. J Biol Chem 273:14912-14919
44. Bae H, Anderson K, Flood LA, Skiba NP, Hamm HE, Graber SG 1997 Molecular determinants of selectivity in 5-hydroxytryptamine1B receptor-G protein interactions. J Biol Chem 272:32071-32077
45. Bae H, Cabrera-Vera TM, Depree KM, Graber SG, Hamm HE 1999 Two amino acids within the α4 helix of Gα1 mediate coupling with 5-hydroxytryptamine1B receptors. J Biol Chem 274:14963-14971
46. Taylor JM, Jacob-Mosier GG, Lawton RG, Remmers AE, Neubig RR 1994 Binding of an α2 adrenergic receptor third intracellular loop peptide to Gβ and the amino terminus of Gα. J Biol Chem 269:27618-27624
47. Onrust R, Herzmark P, Chi P, Garcia PD, Lichtarge O, Kingsley C, Bourne HR 1997 Receptor and βγ binding sites in the α subunit of the retinal G protein transducin. Science 275:381-384
48. Lee CH, Katz A, Simon MI 1995 Multiple regions of Gα 16 contribute to the specificity of activation by the C5a receptor. Mol Pharmacol 47:218-223
49. Mazzoni MR, Hamm HE 1996 Interaction of transducin with light-activated rhodopsin protects it from proteolytic digestion by trypsin. J Biol Chem 271:30034-30040
50. Kisselev O, Pronin A, Ermolaeva M, Gautam N 1995 Receptor-G protein coupling is established by a potential conformational switch in the βγ complex. Proc Natl Acad Sci USA 92:9102-9106
51. Kisselev O, Ermolaeva M, Gautam N 1995 Efficient interaction with a receptor requires a specific type of prenyl group on the G protein γ subunit. J Biol Chem 270:25356-25358
52. Yasuda H, Lindorfer MA, Woodfork KA, Fletcher JE, Garrison JC 1996 Role of the prenyl group on the G protein γ subunit in coupling trimeric G proteins to A1 adenosine receptors. J Biol Chem 271:18588-18595
53. 2a adenosine receptors. J Biol Chem 276:15801-15809
54. 2 generation in human adipocyte plasma membranes is mediated by βγ-subunits derived from Gs. J Biol Chem 275:2486-2490
55. Cismowski MJ, Takesono A, Ma C, Lizano JS, Xie X, Fuernkranz H, Lanier SM, Duzic E 1999 Genetic screens in yeast to identify mammalian nonreceptor modulators of G-protein signaling. Nat Biotechnol 17:878-883
56. Takesono A, Cismowski MJ, Ribas C, Bernard M, Chung P, Hazard 3rd S, Duzic E, Lanier SM 1999 Receptor-independent activators of heterotrimeric G-protein signaling pathways. J Biol Chem 274:33202-33205
57. De Vries L, Fischer T, Tronchere H, Brothers GM, Strockbine B, Siderovski DP, Farquhar MG 2000 Activator of G protein signaling 3 is a guanine dissociation inhibitor for Gαi subunits. Proc Natl Acad Sci USA 97:14364-14369
58. Jamora C, Takizawa PA, Zaarour RF, Denesvre C, Faulkner DJ, Malhotra V 1997 Regulation of Golgi structure through heterotrimeric G proteins. Cell 91:617-626
59. O'Dowd BF, Nguyen T, Tirpak A, Jarvie KR, Israel Y, Seeman P, Niznik HB 1990 Cloning of two additional catecholamine receptors from rat brain. FEBS Lett 262:8-12
60. Van Tol HH 1998 Structural and functional characteristics of the dopamine D4 receptor. Adv Pharmacol 42:486-490
61. Gilchrist A, Bunemann M, Li A, Hosey MM, Hamm HE 1999 A dominant-negative strategy for studying roles of G proteins in vivo. J Biol Chem 274:6610-6616
62. Gilchrist A, Vanhauwe JF, Li A, Thomas TO, Voyno-Yasenetskaya T, Hamm HE 2001 Gα minigenes expressing C-terminal peptides serve as specific inhibitors of thrombin-mediated endothelial activation. J Biol Chem 276:25672-25679
63. Deleted in proof.
64. Walther W, Stein U 1996 Targeted vectors for gene therapy of cancer and retroviral infections. Mol Biotechnol 6:267-286
65. Lutsiak CM, Sosnowski DL, Wishart DS, Kwon GS, Samuel J 1998 Use of a liposome antigen delivery system to alter immune responses in vivo. J Pharm Sci 87:1428-1432
66. 2C receptors in choroid plexus epithelial cells. J Biol Chem 275:7021-7029
67. Akhter SA, Luttrell LM, Rockman HA, Iaccarino G, Lefkowitz RJ, Koch WJ 1998 Targeting the receptor-Gq interface to inhibit in vivo pressure overload myocardial hypertrophy. Science 280:574-577
68. Knall C, Johnson GL 1998 G-protein regulatory pathways: rocketing into the twenty-first century. J Cell Biochem 31:137-146
69. Taussig R, Zimmermann G 1998 Type-specific regulation of mammalian adenylyl cyclases by G protein pathways. Adv Sec Mess Phosphoprot Res 32:81-98
70. Tesmer JJ, Sunahara RK, Gilman AG, Sprang SR 1997 Crystal structure of the catalytic domains of adenylyl cyclase in a complex with GsαGTPγ S. Science 278:1907-1916
71. Berlot CH, Bourne HR 1992 Identification of effector-activating residues of Gsα. Cell 68:911-922
72. Sunahara RK, Dessauer CW, Whisnant RE, Kleuss C, Gilman AG 1997 Interaction of Gsα with the cytosolic domains of mammalian adenylyl cyclase. J Biol Chem 272:22265-22271
73. Chidiac P, Ross EM 1999 Phospholipase C-β1 directly accelerates GTP hydrolysis by Gαq and acceleration is inhibited by Gβγ subunits. J Biol Chem 274:19639-19643
74. 2+ mobilization by dopamine D2S receptors. J Biol Chem 274:9238-9245
75. 2+ entry in rat portal vein myocytes. J Biol Chem 272:5261-5268
76. o with Rap1 GTPase-activating protein. J Biol Chem 274:21507-21510
77. Chen LT, Gilman AG, Kozasa T 1999 A candidate target for G protein action in brain. J Biol Chem 274:26931-26938
78. 2+-binding protein, nucleobindin (CALNUC), is a Golgi resident protein. J Cell Biol 141:1515-1527
79. Mochizuki N, Hibi M, Kanai Y, Insel PA 1995 Interaction of the protein nucleobindin with Gαi2, as revealed by the yeast two-hybrid system. FEBS Lett 373:155-158
80. 2+ binding protein, specifically interacts with the C-terminal α5-helix of Gαi3. Proc Natl Acad Sci USA 97:674-679
81. 2+-binding activity of nucleobindin mediated by an EF hand moiety. Biochem Biophys Res Commun 199:1388-1393
82. q-protein α-subunit. Nature 389:296-299
83. Fields TA, Casey PJ 1997 Signalling functions and biochemical properties of pertussis toxin-resistant G-proteins. Biochem J 321:561-571
84. Hart MJ, Jiang X, Kozasa T, Roscoe W, Singer WD, Gilman AG, Sternweis PC, Bollag G 1998 Direct stimulation of the guanine nucleotide exchange activity of p115 RhoGEF by Gα13. Science 280:2112-2114
85. Vaiskunaite R, Adarichev V, Furthmayr H, Kozasa T, Gudkov A, Voyno-Yasenetskaya TA 2000 Conformational activation of radixin by G13 protein α subunit. J Biol Chem 275:26206-26212
86. Vaiskunaite R, Kozasa T, Voyno-Yasenetskaya TA 2001 Interaction between the Gα subunit of heterotrimeric G12 protein and Hsp90 is required for Gα12 signaling. J Biol Chem 276:46088-46093
87. Neer EJ 1995 Heterotrimeric G proteins: organizers of transmembrane signals. Cell 80:249-257
88. + channel in heart. Nature 325:321-326
89. Katz A, Wu D, Simon MI 1992 Subunits βγ of heterotrimeric G protein activate β2 isoform of phospholipase C. Nature 360:686-689
90. Sternweis PC 1994 The active role of βγ in signal transducrion. Curr Opin Cell Biol 6:198-203
91. Tang WJ, Gilman AG 1991 Type-specific regulation of adenylyl cyclase by G protein βγ subunits. Science 254:1500-1503
92. Pitcher JA, Inglese J, Higgins JB, Arriza JL, Casey PJ, Kim C, Benovic JL, Kwatra MM, Caron MG, Lefkowitz RJ 1992 Role of βγ subunits of G proteins in targeting the β-adrenergic receptor kinase to membrane-bound receptors. Science 257:1264-1267
93. Stephens L, Smrcka A, Cooke FT, Jackson TR, Sternweis PC, Hawkins PT 1994 A novel phosphoinositide 3 kinase activity in myeloid-derived cells is activated by G protein βγ subunits. Cell 77:83-93
94. Tang X, Downes CP 1997 Purification and characterization of Gβγ-responsive phosphoinositide 3-kinases from pig platelet cytosol. J Biol Chem 272:14193-14199
95. Inglese J, Koch WJ, Touhara K, Lefkowitz RJ 1995 Gβγ interactions with PH domains and Ras-MAPK signaling pathways. Trends Biol Sci 20:151-156
96. Reuveny E, Slesinger PA, Inglese J, Morales JM, Iniguez-Lluhi JA, Lefkowitz RJ, Bourne HR, Jan YN, Jan LY 1994 Activation of the cloned muscarinic potassium channel by G protein βγ subunits. Nature 370:143-146
97. Ikeda SR 1996 Voltage-dependent modulation of N-type calcium channels by G-protein βγ subunits. Nature 380:255-258
98. 2+ channels by G-protein βγ subunits. Nature 380:258-262
99. Lupas AN, Lupas JM, Stock JB 1992 Do G-protein subunits associate via a three-stranded coiled coil? FEBS Lett 314:105-108
100. Ray K, Kunsch C, Bonner LM, Robishaw JD 1995 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 270:21765-21771
101. Simon MI, Strathmann MP, Gautam N 1991 Diversity of G proteins in signal transduction. Science 252:802-808
102. Watson AJ, Aragay AM, Slepak VZ, Simon MI 1996 A novel form of the G protein β subunit Gβ5 is specifically expressed in the vertebrate retina. J Biol Chem 271:28154-28160
103. Spring DJ, Neer EJ 1994 A 14-amino acid region of the G protein γ subunit is sufficient to conifer selectivity of γ binding to the β subunit. J Biol Chem 269:22882-22886
104. Schmidt CJ, Thomas TC, Levine MA, Neer EJ 1992 Specificity of G-protein β and γ subunit interaction. J Biol Chem 267:13807-13810
105. Garritsen A, Simonds WF 1994 Multiple domains of G protein β confer subunit specificity in βγ interaction. J Biol Chem 269:24418-24423
106. Yan K, Kalyanaraman V, Gautam N 1996 Differential ability to form the G protein βγ complex among members of the β and γ subunit families. J Biol Chem 271:7141-7146
107. Lindorfer MA, Myung CS, Savino Y, Yasuda H, Khazan R, Garrison JC 1998 Differential activity of the G protein β5γ2 subunit at receptors and effectors. J Biol Chem 273:34429-34436
108. Lei Q, Jones MB, Talley EM, Schrier AD, McIntire WE, Garrison JC, Bayliss DA 2000 Activation and inhibition of G protein-coupled inwardly rectifying potassium (Kir3) channels by G protein βγ subunits. Proc Natl Acad Sci USA 97:9771-9776
109. Fawzi AB, Fay DS, Murphy EA, Tamir H, Erdos JJ, Northup JK 1991 Rhodopsin and the retinal G-protein distinguish among G-protein βγ subunit forms. J Biol Chem 266:12194-12200
110. Tamir H, Fawzi AB, Tamir A, Evans T, Northup JK 1991 G-protein βγ forms: identity of β and diversity of γ subunits. Biochemistry 30:3929-3936
111. Iniguez-Lluhi JA, Simon MI, Robishaw JD, Gilman AG 1992 G protein βγ subunits synthesized in Sf9 cells. J Biol Chem 267:23409-23417
112. Ueda N, Iniguez-Lluhi JA, Lee E, Smrcka AV, Robishaw JD, Gilman AG 1994 G protein βγ subunits. Simplified purification and properties of novel isoforms. J Biol Chem 269:4388-4395
113. Bayewitch ML, Avidor-Reiss T, Levy R, Pfeuffer T, Nevo I, Simonds WF, Vogel Z 1998 Differential modulation of adenylyl cyclases I and II by various G β subunits. J Biol Chem 273:2273-2276
114. Zhang S, Coso OA, Lee C, Gutkind JS, Simonds WF 1996 Selective activation of effector pathways by brain-specific G protein β5. J Biol Chem 271:33535-33539
115. Ruiz-Velasco V, Ikeda SR 2000 Multiple G-protein βγ combinations produce voltage-dependent inhibition of N-type calcium channels in rat superior cervical ganglion neurons. J Neurosci 20:2183-2191
116. Mirshahi T, Mittal V, Zhang H, Linder ME, Logothetis DE 2002 Distinct sites on G protein βγ subunits regulate different effector functions. J Biol Chem 277:36345-36350
117. Fletcher JE, Lindorfer MA, DeFilippo JM, Yasuda H, Guilmard M, Garrison JC 1998 The G protein β5 subunit interacts selectively with the Gqα subunit. J Biol Chem 273:636-644
118. Figler RA, Graber SG, Lindorfer MA, Yasuda H, Linden J, Garrison JC 1996 Reconstitution of recombinant bovine A1 adenosine receptors in Sf9 cell membranes with recombinant G proteins of defined composition. Mol Pharmacol 50:1587-1595
119. Gaudet R, Bohm A, Sigler PB 1996 Crystal structure at 2.4 Å resolution of the complex of transducin βγ and its regulator, phosducin. Cell 87:577-588
120. Panchenko MP, Saxena K, Li Y, Charnecki S, Sternweis PM, Smith TF, Gilman AG, Kozasa T, Neer EJ 1998 Sites important for PLCβ2 activation by the G protein βγ subunit map to the sides of the β propeller structure. J Biol Chem 273:28298-28304
121. Li Y, Sternweis PM, Charnecki S, Smith TF, Gilman AG, Neer EJ, Kozasa T 1998 Sites for Gα binding on the G protein β subunit overlap with sites for regulation of phospholipase Cβ and adenylyl cyclase. J Biol Chem 273:16265-16272
122. Burack WR, Shaw AS 2000 Signal transduction: hanging on a scaffold. Curr Opin Cell Biol 12:211-216
123. Jamora C, Yamanouye N, Van Lint J, Laudenslager J, Vandenheede JR, Faulkner DJ, Malhotra V 1999 Gβγ-mediated regulation of Golgi organization is through the direct activation of protein kinase D. Cell 98:59-68
124. Roychowdhury S, Rasenick MM 1997 G protein β1γ2 subunits promote microtubule assembly. J Biol Chem 272:31576-31581
125. Bell B, Xing H, Yan K, Gautam N, Muslin AJ 1999 KSR-1 binds to G-protein βγ subunits and inhibits βγ-induced mitogen-activated protein kinase activation. J Biol Chem 274:7982-7986
126. Lin HC, Gilman AG 1996 Regulation of dynamin I GTPase activity by G protein βγ subunits and phosphatidylinositol 4,5-bisphosphate. J Biol Chem 271:27979-27982
127. Pumiglia KM, LeVine H, Haske T, Habib T, Jove R, Decker SJ 1995 A direct interaction between G-protein βγ subunits and the Raf-1 protein kinase. J Biol Chem 270:4251-4254
128. Langhans-Rajasekaran SA, Wan Y, Huang XY 1995 Activation of Tsk and Btk tyrosine kinases by G protein βγ subunits. Proc Natl Acad Sci USA 92:8601-8605
129. 2+-dependent binding of calmodulin to an N-terminal motif of the heterotrimeric G protein β subunit. J Biol Chem 272:18801-18807
130. Pellegrino S, Zhang S, Garritsen A, Simonds WF 1997 The coiled-coil region of the G protein β subunit. Mutational analysis of Gγ and effector interactions. J Biol Chem 272:25360-25366
131. Dell EJ, Connor J, Chen S, Stebbins EG, Skiba NP, Mochly-Rosen D, Hamm HE 2002 The βγ subunit of heterotrimeric G proteins interacts with RACK1 and two other WD repeat proteins. J Biol Chem 277:49888-49895
132. 2+ entry. Science 292:293-297
133. Gautam N, Downes GB, Yan K, Kisselev O 1998 The G-protein βγ complex. Cell Signal 10:447-455
134. Watson AJ, Katz A, Simon MI 1994 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 269:22150-22156
135. Garritsen A, van Galen PJ, Simonds WF 1993 The N-terminal coiled-coil doman of β is essential for γ association: a model for G-protein βγ subunit interaction. Proc Natl Acad Sci USA 90:7706-7710
136. Cabrera JL, de Freitas F, Satpaev DK, Slepak VZ 1998 Identification of the Gβ5-RGS7 protein complex in the retina. Biochem Biophys Res Commun 249:898-902
137. Yoshikawa DM, Hatwar M, Smrcka AV 2000 G protein β5 subunit interactions with α subunits and effectors. Biochemistry 39:11340-11347
138. Makino ER, Handy JW, Li T, Arshavsky VY 1999 The GTPase activating factor for transducin in rod photoreceptors is the complex between RGS9 and type 5 G protein β subunit. Proc Natl Acad Sci USA 96:1947-1952
139. Levay K, Cabrera JL, Satpaev DK, Slepak VZ 1999 Gβ5 prevents the RGS7-Gαo interaction through binding to a distinct Gγ-like domain found in RGS7 and other RGS proteins. Proc Natl Acad Sci USA 96:2503-2507
140. Snow BE, Krumins AM, Brothers GM, Lee SF, Wall MA, Chung S, Mangion J, Arya S, Gilman AG, Siderovski DP 1998 A G protein γ subunit-like domain shared between RGS11 and other RGS proteins specifies binding to Gβ5 subunits. Proc Natl Acad Sci USA 95:13307-13312
141. Kovoor A, Chen CK, He W, Wensel TG, Simon MI, Lester HA 2000 Co-expression of Gβ5 enhances the function of two Gγ subunit-like domain-containing regulators of G protein signaling proteins. J Biol Chem 275:3397-3402
142. Posner BA, Gilman AG, Harris BA 1999 Regulators of G protein signalling 6 and 7. J Biol Chem 274:31087-31093
143. Chen CK, Burns ME, He W, Wensel TG, Baylor DA, Simon MI 2000 Slowed recovery of rod photoresponse in mice lacking the GTPase accelerating protein RGS9-1. Nature 403:557-560
144. Graziano MP, Freissmuth M, Gilman AG 1989 Expression of Gs α in Escherichia coli. Purification and properties of two forms of the protein. J Biol Chem 264:409-418
145. 2+ on the GTPase activity and the fluorescent properties of Go. J Biol Chem 262:757-761
146. Warner DR, Weinstein LS 1999 A mutation in the heterotrimeric stimulatory guanine nucleotide binding protein α-subunit with impaired receptor-mediated activation because of elevated GTPase activity. Proc Natl Acad Sci USA 96:4268-4272
147. Arshavsky VY, Pugh EN 1998 Lifetime regulation of G protein effector complex: emerging importance of RGS proteins. Neuron 20:11-14
148. Zerangue N, Jan LY 1998 G-protein signaling: fine-tuning signaling kinetics. Curr Biol 8:R313-R316
149. Bernstein G, Blank JL, Jhon DY, Exton JH, Rhee SG, Ross EM 1992 Phospholipase C-β1 is a GTPase-activating protein for Gq/11, its physiologic regulator. Cell 70:411-418
150. Biddlecome GH, Berstein G, Ross EM 1996 Regulation of phospholipase C-β1 by Gq and m1 muscarinic cholinergic receptor. Steady-state balance of receptor-mediated activation and GTPase-activating protein-promoted deactivation. J Biol Chem 271:7999-8007
151. Arshavsky VY, Bownds MD 1992 Regulation of deactivation of photoreceptor G protein by its target enzyme and cGMP. Nature 357:416-417
152. Scholich K, Mullenix JB, Wittpoth C, Poppleton HM, Pierre SC, Lindorfer MA, Garrison JC, Patel TB 1999 Facilitation of signal onset and termination by adenylyl cyclase. Science 283:1328-1331
153. Bunemann M, Hosey MM 1998 Regulators of G protein signaling (RGS) proteins constitutively activate Gβγ-gated potassium channels. J Biol Chem 273:31186-31190
154. De Vries L, Zheng B, Fischer T, Elenko E, Farquhar MG 2000 The regulator of G protein signaling family. Annu Rev Pharmacol Toxicol 40:235-271
155. Ross EM, Wilkie TM 2000 GTPase-activating proteins for heterotrimeric G proteins: regulators of G protein signaling (RGS) and RGS-like proteins. Annu Rev Biochem 69:795-827
156. Hollinger S, Hepler JR 2002 Cellular regulation of RGS proteins: modulators and integrators of G protein signaling. Pharmacol Rev 54:527-559
157. Dohlman HG, Song J, Ma D, Courchesne WE, Thorner J 1996 Sst2, a negative regulator of pheromone signaling in the yeast Saccharomyces cerevisiae: expression, localization, and genetic interaction and physical association with Gpα1 (the G-protein α subunit). Mol Cell Biol 16:5194-5209
158. Koelle MR, Horvitz HR 1996 EGL-10 regulates G protein signaling in the C. elegans nervous system and shares a conserved domain with many mammalian proteins. Cell 84:115-125
159. De Vries L, Mousli M, Wurmser A, Farquhar MG 1995 GAIP, a protein that specifically interacts with the trimeric G protein Gαi3, is a member of a protein family with a highly conserved core domain. Proc Natl Acad Sci USA 92:11916-11920
160. Chen C, Zheng B, Han J, Lin S-C 1997 Characterization of a novel mammalian RGS protein that binds to Gα proteins and inhibits pheromone signaling in yeast. J Biol Chem 272:8679-8685
161. Dohlman HG, Thorner J 1997 RGS proteins and signaling by heterotrimeric G proteins. J Biol Chem 272:3871-3874
162. He W, Cowan CW, Wensel TG 1998 RGS9, a GTPase accelerator for phototransduction. Neuron 20:95-102
163. Skiba NP, Yang C-S, Huang T, Bae H, Hamm HE 1999 The α helical domain of Gαt determines specific interaction with RGS9. J Biol Chem 274:8770-8778
164. Chen C, Lin SC 1998 The core domain of RGS16 retains G-protein binding and GAP activity in vitro, but is not functional in vivo. FEBS Lett 422:359-362
165. He W, Lu L, Zhang X, El-Hodiri HM, Chen CK, Slep KC, Simon MI, Jamrich M, Wensel TG 2000 Modules in the photoreceptor RGS9-1.Gβ 5L GTPase-accelerating protein complex control effector coupling, GTPase acceleration, protein folding, and stability. J Biol Chem 275:37093-37100
166. Siderovski DP, Strockbine B, Behe CI 1999 Whither goest the RGS proteins? Crit Rev Biochem Mol Biol 34:215-251
167. --activated Giα1: stabilization of the transition state for GTP hydrolysis. Cell 89:251-261
168. Mukhopadhyay S, Ross EM 1999 Rapid GTP binding and hydrolysis by Gq promoted by receptor and GTPase-activating proteins. Proc Natl Acad Sci USA 96:9539-9544
169. Yong-Chao Ma, Jianyun Huang, Shariq Ali, William Lowry, Xin-Yun Huang 2000 Src tyrosine kinase is a novel direct effector of G proteins. Cell 102:635-646
170. Skiba NP, Hopp JA, Arshavsky VY 2000 The effector enzyme regulates the duration of G protein signaling in vertebrate photoreceptors by increasing the affinity between transducin and RGS protein. J Biol Chem 275:32716-32720
171. Bushfield M, Murphy GJ, Lavan BE, Parker PJ, Hruby VJ, Milligan G, Houslay MD 1990 Hormonal regulation of Gi2α-subunit phosphorylation in intact hepatocytes. Biochem J 268:449-457
172. Strassheim D, Malbon CC 1994 Phosphorylation of Giα2 attenuates inhibitory adenylyl cyclase in neuroblastoma/glioma hybrid (NG-108-15) cells. J Biol Chem 269:14307-14313
173. Murthy KS, Grider JR, Makhlouf GM 2000 Heterologous desensitization of response mediated by selective PKC-dependent phosphorylation of Gi-1 and Gi-2. Am J Physiol Cell Physiol 279:C925-C934
174. Chen CA, Manning DR 2001 Regulation of G proteins by covalent modification. Oncogene 20:1643-1652
175. Fields TA, Casey PJ 1995 Phosphorylation of Gzα by protein kinase C blocks interaction with the βγ complex. J Biol Chem 270:23119-23125
176. Carlson KE, Brass LF, Manning DR 1989 Thrombin and phorbol esters cause the selective phosphorylation of a G protein other than Gi in human platelets. J Biol Chem 264:13298-13305
177. Glick JL, Meigs TE, Miron A, Casey PJ 1998 RGSZ1, a Gz-selective regulator of G protein signaling whose action is sensitive to the phosphorylation state of Gzα. J Biol Chem 273:26008-26013
178. Moyers JS, Linder ME, Shannon JD, Parsons SJ 1995 Identification of the in vitro phosphorylation sites on Gsα mediated by pp60c-src. Biochemistry 305:411-417
179. Zick Y, Sagi-Eisenberg R, Pines M, Gierschik P, Spiegel AM 1986 Multisite phosphorylation of the a subunit of transducin by the insulin receptor kinase and protein kinase C. Proc Natl Acad Sci USA 83:9294-9297
180. Kozasa T, Gilman AG 1996 Protein kinase C phosphorylates G12α and inhibits its interaction with Gβγ. J Biol Chem 271:12562-12567
181. Wieland T, Nurnberg B, Ulibarri I, Kaldenberg-Stasch S, Schultz G, Jakobs KH 1993 Guanine nucleotide-specific phosphate transfer by guanine nucleotide-binding regulatory protein β-subunits. Characterization of the phosphorylated amino acid. J Biol Chem 268:18111-18118
182. Asano T, Morishita R, Ueda H, Asano M, Kato K 1998 GTP-binding protein γ12 subunit phosphorylation by protein kinase C. Identification of the phosphorylation site and factors involved in cultured cells and rat tissues in vivo. Eur J Biochem 251:314-319
183. Yasuda H, Lindorfer MA, Myung C-S, Garrison JC 1998 Phosphorylation of the G protein γ12 subunit regulates effector specificity. J Biol Chem 273:21958-21965
184. Mumby SM, Heukeroth RO, Gordon JI, Gilman AG 1990 G-protein α-subunit expression, myristoylation, and membrane association in COS cells. Proc Natl Acad Sci USA 87:728-732
185. Milligan G, Grassie MA 1997 How do G proteins stay at the plasma membrane. Essays Biochem 32:49-60
186. Wedegaertner PB 1998 Lipid modifications and membrane targeting of Gα. Biol Signals Recept 7:125-135
187. Resh MD 1999 Fatty acylation of proteins: new insights into membrane targeting of myristoylated and palmitoylated proteins. Biochim Biophys Acta 1451:1-16
188. Mumby SM 1997 Reversible palmitoylation of signaling proteins. Curr Opin Cell Biol 9:148-154
189. Dunphy JT, Linder ME 1998 Signaling function of protein palmitoylation. Biochim Biophys Acta 1436:245-261
190. Milligan G, Parenti M, Magee AI 1995 The dynamic role of palmitoylation in signal transduction. Trends Biochem Sci 20:181-186
191. Zang FL, Casey PJ 1996 Protein prenylation: molecular mechanisms and functional consequences. Annu Rev Biochem 65:241-269
192. Casey PJ 1995 Mechanisms of protein prenylation and role in G protein function. Biochem Soc Trans 23:161-166
193. 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
194. Degtyarev MY, Spiegel AM, Jones TLZ 1994 Palmitoylation of a G protein αi subunit requires membrane localization not myristoylation. J Biol Chem 269:30898-30903
195. Morales J, Fishburn CS, Wilson PT, Bourne HR 1998 Plasma membrane localization of Gαz requires two signals. Mol Biol Cell 10:1-14
196. Mumby SM, Kleuss C, Gilman AG 1994 Receptor regulation of G-protein palmitoylation. Proc Natl Acad Sci USA 91:2800-2804
197. Wise A, Grassie MA, Parenti M, Lee M, Rees S, Milligan G 1997 A cysteine-3 to serine mutation of the G-protein Gi1α abrogates functional activation by the α2A-adrenoceptor but not interactions with the βγ complex. Biochemistry 36:10620-10629
198. Hallak H, Brass L, Manning D 1994 Failure to myristoylate the α subunit of Gz is correlated with an inhibition of palmitoylation and membrane attachment, but has no affect on phosphorylation by protein kinase C. J Biol Chem 269:4571-4576
199. Wilson PT, Bourne HR 1995 Fatty acylation of αz. Eeffects of palmitoylation and myristoylation on αz signaling. J Biol Chem 270:9667-9675
200. Shahinian S, Silvius JR 1995 Doubly-lipid-modified protein sequence motifs exhibit long-lived anchorage to lipid bilayer membranes. Biochemistry 34:3813-3822
201. McCabe JB, Berthiaume LG 1999 Functional roles for fatty acylated amino-terminal domains in subcellular localization. Mol Biol Cell 10:3771-3786
202. Wang Y, Windh RT, Chen CA, Manning DR 1999 N-Myristoylation and βγ play roles beyond anchorage in the palmitoylation of the G protein αo subunit. J Biol Chem 274:37435-37442
203. Wedegaertner P, Chu D, Wilson P, Levis M, Bourne H 1993 Palmitoylation is required for signaling functions and membrane attachment of Gqα and Gsα. J Biol Chem 268:25001-25008
204. 3H]palmitic acid and mutation of cysteine-3 prevents this modification. Biochemistry 32:8057-8061
205. Wise A, Parenti M, Milligan G 1997 Interaction of the G-protein G11α with receptors and phosphoinositidase C:the contribution of G-protein palmitoylation and membrane association. FEBS Lett 407:257-260
206. Bhattacharyya R, Wedegaetner PB 2000 Gα13 requires palmitoylation for plasma membrane localization, Rho-dependent signaling, and promotion of p115-RhoGEF membrane binding. J Biol Chem 275:14992-14999
207. Evanko DS, Thiygarajan MM, Wedegaertner PB 2000 Interaction with Gβγ is required for membrane targeting and palmitoylation of Gαs and Gαq. J Biol Chem 275:1327-1336
208. Hepler J, Biddlecome G, Kleuss C, Camp L, Hofmann S, Ross E, Gilman A 1996 Functional importance of the amino terminus of Gqα. J Biol Chem 271:496-504
209. Fishburn CS, Pollitt SK, Bourne HR 2000 Localization of a peripheral membrane protein: Gβγ targets Gαz. Proc Natl Acad Sci USA 97:1085-1090
210. Linder ME, Pang IH, Duronio RJ, Gordon JI, Sternweis PC, Gilman AG 1991 Lipid modifications of G protein subunits. Myristoylation of Goα increases its affinity for βγ. J Biol Chem 266:4654-4659
211. Taussig R, Iniguez-Lluhi JA, Gilman AG 1993 Inhibition of adenylyl cyclase by Giα. Science 261:218-221
212. Iiri T, Backlund Jr PS, Jones TL, Wedegaertner PB, Bourne HR 1996 Reciprocal regulation of Gsα by palmitate and the βγ subunit. Proc Natl Acad Sci USA 93:14592-14597
213. Tu Y, Wang J, Ross EM 1997 Inhibition of brain GzGAP and other RGS proteins by palmitoylation of G protein a subunits. Science 278:1132-1135
214. Degtyarev MY, Spiegel AM, Jones TLZ 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
215. Wedegaertner PB, Wilson PT, Bourne HR 1995 Lipid modifications of trimeric G proteins. J Biol Chem 270:503-506
216. Matsuda T, Hashimoto Y, Ueda H, Asano T, Matsuura Y, Doi T, Takao T, Shimonishi Y, Fukada Y 1998 Specific isoprenyl group linked to transducin γ-subunit is a determinant of its unique signaling properties among G-proteins. Biochemistry 37:9843-9850
217. Schwindinger WF, Robishaw JD 2001 Heterotrimeric G-protein βγ-dimers in growth and differentiation. Oncogene 20:1653-1660
218. Myung CS, Yasuda H, Liu WW, Harden TK, Garrison JC 1999 Role of isoprenoid lipids on the heterotrimeric G protein γ subunit in determining effector activation. J Biol Chem 274:16595-16603
219. Parish CA, Smrcka AV, Rando RR 1995 Functional significance of βγ subunit carboxymethylation for the activation of phospholipase C and phosphoinositide 3-kinase. Biochemistry 34:7722-7727
220. Leopoldt D, Hanck T, Exner T, Maier U, Wetzker R, Nurnberg B 1998 Gβγ stimulates phosphoinositide 3-kinase-γ by direct interaction with two domains of the catalytic p110 subunit. J Biol Chem 273:7024-7029
221. Erickson JW, Cerione RA 1991 Resonance energy transfer as a direct monitor of GTP-binding protein-effector interactions: activated α-transducin binding to the cGMP phosphodiesterase in the bovine phototransduction cascade. Biochemistry 30:7112-7118
222. Remmers AE 1998 Detection and quantitation of heterotrimeric G proteins by fluorescence resonance energy transfer. Anal Biochem 257:89-94
223. Lan KL, Remmers AE, Neubig RR 1998 Roles of Goα tryptophans in GTP hydrolysis, GDP release, and fluorescence signals. Biochemistry 37:837-843
224. Farrens DL, Altenbach C, Yang K, Hubbell WL, Khorana HG 1996 Requirement of rigid-body motion of transmembrane helices for light activation of rhodopsin. Science 274:768-770
225. Medkova M, Preininger AM, Yu NJ, Hubbell WL, Hamm HE 2002 Conformational changes in the amino-terminal helix of the G protein αi1 following dissociation from Gβγ subunit and activation. Biochemistry 41:9962-9972
226. Figler RA, Lindorfer MA, Graber SG, Garrison JC, Linden J 1997 Reconstitution of bovine A1 adenosine receptors and G proteins in phospholipid vesicles: βγ-subunit composition influences guanine nucleotide exchange and agonist binding. Biochemistry 36:16288-16299
227. Cooper MA, Hansson A, Lofas S, Williams DH 2000 A vesicle capture sensor chip for kinetic analysis of interactions with membrane-bound receptors. Anal Biochem 277:196-205
228. Ram PT, Iyengar R 2001 G protein coupled receptor signaling through the Src and Stat3 pathway: role in proliferation and transformation. Oncogene 20:1601-1606
229. 2+ channels. J Biol Chem 276:28731-28738
230. + channel, GIRK. Neuron 33:87-99
231. Roychowdhury S, Panda D, Wilson L, Rasenick MM 1999 G protein α subunits activate tubulin GTPase and modulate microtubule polymerization dynamics. J Biol Chem 274:13485-13490
232. + exchanger by Gα12 class of G proteins. J Biol Chem 269:11802-11806
233. Plonk SG, Park SK, Exton JH 1998 The α-subunit of the heterotrimeric G protein G13 activates a phospholipase D isozyme by a pathway requiring Rho family GTPases. J Biol Chem 273:4823-4826
234. Kitamura K, Singer WD, Star RA, Muallem S, Miller RT 1996 Induction of inducible nitric-oxide synthase by the heterotrimeric G protein Gα13. J Biol Chem 271:7412-7415
235. Touhara K, Hawes BE, van Biesen T, Lefkowitz RJ 1995 G protein βγ subunits stimulate phosphorylarion of Shc adapter protein. Proc Natl Acad Sci USA 92:9284-9287
236. Mattingly RR, Macara IG 1996 Phosphorylation-dependent activation of the Ras-GRF/CDC25Mm exchange factor by muscarinic receptors and G-protein βγ subunits. Nature 382:268-272
237. Sunahara RK, Tesmer JJ, Gilman AG, Sprang SR 1997 Crystal structure of the adenylyl cyclase activator Gsα. Science 278:1943-1947
238. Mixon MB, Lee E, Coleman DE, Berghuis AM, Gilman AG, Sprang SR 1995 Tertiary and quaternary structural changes in Giα1 induced by GTP hydrolysis. Science 270:954-960
239. Sondek J, Bohm A, Lambright DG, Hamm HE, Sigler PB 1996 Crystal structure of a G protein βγ dimer at 2.1 Å resolution. Nature 379:369-374
240. Palczewski K, Kumasaka T, Hori T, Behnke CA, Motoshima H, Fox BA, Le Trong I, Teller DC, Okada T, Stenkamp RE, Yamamoto M, Miyano M 2000 Crystal structure of rhodopsin: A G protein-coupled receptor. Science 289:739-745
241. Neves SR, Ram PT, Iyengar R 2002 G protein pathways. Science 296:1636-1639