Heterotrimeric G Proteins and Their Effector Pathways

Contemporary Clinical Neuroscience

Volumn , Issue , 2005, Pages 109-134

  Hwangpo, Tracy Nguyen ^a   Iyengar, Ravi ^a  

^a MOUNT SINAI SCHOOL OF MEDICINE   (United States)

Author keywords

Adenylyl Cyclase; Direct Effector; Growth Cone; Neurite Outgrowth; Protein Alpha Subunit

Indexed keywords

EID: 84978028137     PISSN: 2627535X     EISSN: 26275341     Source Type: Book Series    
DOI: 10.1007/978-1-59259-919-6_5     Document Type: Chapter

References (120)

1. Ross EM, Gilman AG. Biochemical properties of hormone-sensitive adenylate cyclase. Annu Rev Biochem 1980;49:533–564.
2. Rodbell M. The role of hormone receptors and GTP-regulatory proteins in membrane transduction. Nature 1980;284:17–22.
3. Gilman AG. G proteins: transducers of receptor-generated signals. Annu Rev Biochem 1987;56:615–649.
4. Schoneberg T. GPCR Superfamily and Its Structural Characterization. In: Pangalos MaD, CH, ed. Understanding G Protein-Coupled Receptors and Their Role in the CNS. 1st ed. New York: Oxford University Press, 2002, pp. 3–27.
5. George SR, O’Dowd BF, Lee SP. G-protein-coupled receptor oligomerization and its potential for drug discovery. Nat Rev Drug Discov 2002;1:808–820.
6. Ulrich CD 2nd, Holtmann M, Miller LJ. Secretin and vasoactive intestinal peptide receptors: members of a unique family of G protein-coupled receptors. Gastroenterology 1998;114:382–897.
7. Horn F, Weare J, Beukers MW, et al. GPCRDB: an information system for G protein-coupled receptors. Nucleic Acids Res 1998;26:275–279.
8. Horn F, Bettler E, Oliveira L, Campagne F, Cohen FE, Vriend G. GPCRDB information system for G protein-coupled receptors. Nucleic Acids Res 2003;31:294–297.
9. Hollinger S, Hepler JR. Cellular regulation of RGS proteins: modulators and integrators of G protein signaling. Pharmacol Rev 2002;54:527–559.
10. Cismowski MJ, Takesono A, Bernard ML, Duzic E, Lanier SM. Receptor-independent activators of heterotrimeric G-proteins. Life Sci 2001;68:2301–2308.
11. Ferguson SS. Evolving concepts in G protein-coupled receptor endocytosis: the role in receptor desensitization and signaling. Pharmacol Rev 2001;53:1–24.
12. Ho MaW, YH. G Protein Structure Diversity. In: Pangalos MaD, CH, ed. Understanding G Protein-Coupled Receptors and Their Role in the CNS. 1st ed. New York: Oxford University Press,2002, pp. 63–86.
13. Offermanns S. G-proteins as transducers in transmembrane signalling. Prog Biophys Mol Biol 2003;83:101–130.
14. Cabrera-Vera TM, Vanhauwe J, Thomas TO, et al. Insights into G protein structure, function, and regulation. Endocr Rev 2003;24:765–781.
15. Weinstein LS, Chen M, Liu J. Gs(alpha) mutations and imprinting defects in human disease. Ann NY Acad Sci 2002;968:173–197.
16. Kehlenbach RH, Matthey J, Huttner WB. XL alpha s is a new type of G protein. Nature 1994;372:804–809.
17. Klemke M, Pasolli HA, Kehlenbach RH, Offermanns S, Schultz G, Huttner WB. Characterization of the extra-large G protein alpha-subunit XLalphas. II. Signal transduction properties. J Biol Chem 2000;275:33,633–33,640.
18. Bastepe M, Gunes Y, Perez-Villamil B, Hunzelman J, Weinstein LS, Juppner H. Receptor-mediated adenylyl cyclase activation through XLalpha(s), the extra-large variant of the stimulatory G protein alpha-subunit. Mol Endocrinol 2002;16:1912–1919.
19. Jones DT, Reed RR. Golf: an olfactory neuron specific-G protein involved in odorant signal transduction. Science 1989;244:790–795.
20. Jones DT, Masters SB, Bourne HR, Reed RR. Biochemical characterization of three stimulatory GTP-binding proteins. The large and small forms of Gs and the olfactory-specific G-protein, Golf. J Biol Chem 1990;265:2671–2676.
21. Belluscio L, Gold GH, Nemes A, Axel R. Mice deficient in G(olf) are anosmic. Neuron 1998;20:69–81.
22. Ebrahimi FA, Chess A. Olfactory G proteins: simple and complex signal transduction. Curr Biol 1998;8:R431–R433.
23. Regnauld K, Nguyen QD, Vakaet L, et al. G-protein alpha(olf) subunit promotes cellular invasion, survival, and neuroendocrine differentiation in digestive and urogenital epithelial cells. Oncogene 2002;21:4020–4031.
24. Itoh H, Toyama R, Kozasa T, Tsukamoto T, Matsuoka M, Kaziro Y. Presence of three distinct molecular species of Gi protein alpha subunit. Structure of rat cDNAs and human genomic DNAs. J Biol Chem 1988;263:6656–6664.
25. Sunahara RK, Dessauer CW, Gilman AG. Complexity and diversity of mammalian adenylyl cyclases. Annu Rev Pharmacol Toxicol 1996;36:461–480.
26. Dalwadi H, Wei B, Schrage M, Su TT, Rawlings DJ, Braun J. B cell developmental requirement for the G alpha i2 gene. J Immunol 2003;170:1707–1715.
27. Huang TT, Zong Y, Dalwadi H, et al. TCR-mediated hyper-responsiveness of autoimmune Galphai2(-/-) mice is an intrinsic naive CD4(+) T cell disorder selective for the Galphai2 subunit. Int Immunol 2003;15:1359–1367.
28. Strathmann M, Wilkie TM, Simon MI. Alternative splicing produces transcripts encoding two forms of the alpha subunit of GTP-binding protein Go. Proc Natl Acad Sci USA 1990;87:6477–6481.
29. Hsu WH, Rudolph U, Sanford J, et al. Molecular cloning of a novel splice variant of the alpha subunit of the mammalian Go protein. J Biol Chem 1990;265:11,220–11,226.
30. Exner T, Jensen ON, Mann M, Kleuss C, Nurnberg B. Posttranslational modification of Galphao1 generates Galphao3, an abundant G protein in brain. Proc Natl Acad Sci USA 1999;96:1327–1332.
31. Strittmatter SM, Valenzuela D, Kennedy TE, Neer EJ, Fishman MC. G0 is a major growth cone protein subject to regulation by GAP-43. Nature 1990;344:836–841.
32. Strittmatter SM, Fishman MC, Zhu XP. Activated mutants of the alpha subunit of G(o) promote an increased number of neurites per cell. J Neurosci 1994;14:2327–2338.
33. Jordan JD, Carey KD, Stork PJ, Iyengar R. Modulation of rap activity by direct interaction of Galpha(o) with Rap1 GTPase-activating protein. J Biol Chem 1999;274:21,507–21,510.
34. Chen LT, Gilman AG, Kozasa T. A candidate target for G protein action in brain. J Biol Chem 1999;274:26,931–26,938.
35. Ho MK, Wong YH. G(z) signaling: emerging divergence from G(i) signaling. Oncogene 2001;20:1615–1625.
36. Wong YH, Conklin BR, Bourne HR. Gz-mediated hormonal inhibition of cyclic AMP accumulation. Science 1992;255:339–342.
37. Jeong SW, Ikeda SR. G protein alpha subunit G alpha z couples neurotransmitter receptors to ion channels in sympathetic neurons. Neuron 1998;21:1201–1212.
38. Fong HK, Yoshimoto KK, Eversole-Cire P, Simon MI. Identification of a GTP-binding protein alpha subunit that lacks an apparent ADP-ribosylation site for pertussis toxin. Proc Natl Acad Sci USA 1988;85:3066–3070.
39. Matsuoka M, Itoh H, Kozasa T, Kaziro Y. Sequence analysis of cDNA and genomic DNA for a putative pertussis toxin-insensitive guanine nucleotidebinding regulatory protein alpha subunit. Proc Natl Acad Sci USA 1988;85:5384–5388.
40. Casey PJ, Fong HK, Simon MI, Gilman AG. Gz, a guanine nucleotide-binding protein with unique biochemical properties. J Biol Chem 1990;265:2383–2390.
41. Fields TA, Casey PJ. Phosphorylation of Gz alpha by protein kinase C blocks interaction with the beta gamma complex. J Biol Chem 1995;270:23,119–23,125.
42. Wang J, Frost JA, Cobb MH, Ross EM. Reciprocal signaling between heterotrimeric G proteins and the p21-stimulated protein kinase. J Biol Chem 1999;274:31,641–31,647.
43. Wong GT, Gannon KS, Margolskee RF. Transduction of bitter and sweet taste by gustducin. Nature 1996;381:796–800.
44. Margolskee RF. Molecular mechanisms of bitter and sweet taste transduction. J Biol Chem 2002;277:1–4.
45. Zhang Y, Hoon MA, Chandrashekar J, et al. Coding of sweet, bitter, and umami tastes: different receptor cells sharing similar signaling pathways. Cell 2003;112:293–301.
46. Burns ME, Baylor DA. Activation, deactivation, and adaptation in vertebrate photoreceptor cells. Annu Rev Neurosci 2001;24:779–805.
47. Fain GL, Matthews HR, Cornwall MC, Koutalos Y. Adaptation in vertebrate photoreceptors. Physiol Rev 2001;81:117–151.
48. Arshavsky VY, Lamb TD, Pugh EN Jr. G proteins and phototransduction. Annu Rev Physiol 2002;64:153–187.
49. Exton JH. Regulation of phosphoinositide phospholipases by hormones, neurotransmitters, and other agonists linked to G proteins. Annu Rev Pharmacol Toxicol 1996;36:481–509.
50. Rebecchi MJ, Pentyala SN. Structure, function, and control of phosphoinositide-specific phospholipase C. Physiol Rev 2000;80:1291–1335.
51. Rhee SG. Regulation of phosphoinositide-specific phospholipase C. Annu Rev Biochem 2001;70:281–312.
52. Wilkie TM, Scherle PA, Strathmann MP, Slepak VZ, Simon MI. Characterization of G-protein alpha subunits in the Gq class: expression in murine tissues and in stromal and hematopoietic cell lines. Proc Natl Acad Sci USA 1991;88:10,049–10,053.
53. Amatruda TT, Steele DA, Slepak VZ, Simon MI. G alpha 16, a G protein alpha subunit specifically expressed in hematopoietic cells. Proc Natl Acad Sci USA 1991; 88:5587–5591.
54. Kuang Y, Wu Y, Jiang H, Wu D. Selective G protein coupling by C-C chemokine receptors. J Biol Chem 1996;271:3975–3978.
55. Strathmann MP, Simon MI. G alpha 12 and G alpha 13 subunits define a fourth class of G protein alpha subunits. Proc Natl Acad Sci USA 1991;88:5582–5586.
56. Milligan G, Mullaney I, Mitchell FM. Immunological identification of the alpha subunit of G13, a novel guanine nucleotide binding protein. FEBS Lett 1992;297:186–188.
57. Kurose H. Galpha12 and Galpha13 as key regulatory mediator in signal transduction. Life Sci 2003;74:155–161.
58. Collins LR, Minden A, Karin M, Brown JH. Galpha12 stimulates c-Jun NH2 terminal kinase through the small G proteins Ras and Rac. J Biol Chem 1996;271:17,349–17,353.
59. Voyno-Yasenetskaya TA, Faure MP, Ahn NG, Bourne HR. Galpha12 and Galpha13 regulate extracellular signal-regulated kinase and c-Jun kinase pathways by different mechanisms in COS-7 cells. J Biol Chem 1996;271:21,081–21,087.
60. Hooley R, Yu CY, Symons M, Barber DL. G alpha 13 stimulates Na+-H+ exchange through distinct Cdc42-dependent and RhoA-dependent pathways. J Biol Chem 1996;271:6152–6158.
61. Lin X, Voyno-Yasenetskaya TA, Hooley R, Lin CY, Orlowski J, Barber DL. Galpha12 differentially regulates Na+-H+ exchanger isoforms. J Biol Chem 1996;271:22,604–22,610.
62. Plonk SG, Park SK, Exton JH. The alpha-subunit of the heterotrimeric G protein G13 activates a phospholipase D isozyme by a pathway requiring Rho family GTPases. J Biol Chem 1998;273:4823–4826.
63. Nagao M, Kaziro Y, Itoh H. The Src family tyrosine kinase is involved in Rho-dependent activation of c-Jun N-terminal kinase by Galpha12. Oncogene 1999;18:4425–4434.
64. Dhanasekaran N, Dermott JM. Signaling by the G12 class of G proteins. Cell Signal 1996;8:235–245.
65. Fromm C, Coso OA, Montaner S, Xu N, Gutkind JS. The small GTP-binding protein Rho links G protein-coupled receptors and Galpha12 to the serum response element and to cellular transformation. Proc Natl Acad Sci USA 1997;94:10,098–10,103.
66. Fukuhara S, Chikumi H, Gutkind JS. RGS-containing RhoGEFs: the missing link between transforming G proteins and Rho? Oncogene 2001;20:1661–1668.
67. Offermanns S. In vivo functions of heterotrimeric G-proteins: studies in Galpha-deficient mice. Oncogene 2001;20:1635–1642.
68. Suzuki N, Nakamura S, Mano H, Kozasa T. Galpha 12 activates Rho GTPase through tyrosine-phosphorylated leukemia-associated RhoGEF. Proc Natl Acad Sci USA 2003;100:733–738.
69. Clapham DE, Neer EJ. G protein beta gamma subunits. Annu Rev Pharmacol Toxicol 1997;37:167–203.
70. Gautam N, Downes GB, Yan K, Kisselev O. The G-protein betagamma complex. Cell Signal 1998;10:447–455.
71. Schwindinger WF, Robishaw JD. Heterotrimeric G-protein betagammadimers in growth and differentiation. Oncogene 2001;20:1653–1660.
72. Yan K, Kalyanaraman V, Gautam N. Differential ability to form the G protein betagamma complex among members of the beta and gamma subunit families. J Biol Chem 1996;271:7141–7146.
73. Wang Q, Mullah BK, Robishaw JD. Ribozyme approach identifies a functional association between the G protein beta1gamma7 subunits in the betaadrenergic receptor signaling pathway. J Biol Chem 1999;274:17,365–17,371.
74. Asano T, Morishita R, Ueda H, Kato K. Selective association of G protein beta(4) with gamma(5) and gamma(12) subunits in bovine tissues. J Biol Chem 1999;274:21,425–21,429.
75. Logothetis DE, Kurachi Y, Galper J, Neer EJ, Clapham DE. The beta gamma subunits of GTP-binding proteins activate the muscarinic K+ channel in heart. Nature 1987;325:321–326.
76. Hanoune J, Defer N. Regulation and role of adenylyl cyclase isoforms. Annu Rev Pharmacol Toxicol 2001;41:145–174.
77. de Rooij J, Zwartkruis FJ, Verheijen MH, et al. Epac is a Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP. Nature 1998;396:474–477.
78. Kawasaki H, Springett GM, Mochizuki N, et al. A family of cAMP-binding proteins that directly activate Rap1. Science 1998;282:2275–2279.
79. Defer N, Best-Belpomme M, Hanoune J. Tissue specificity and physiological relevance of various isoforms of adenylyl cyclase. Am J Physiol Renal Physiol 2000;279:F400–F416.
80. Hieble JaRJ, RR. Adrenergic Receptors. In: Pangalos MN and Davies CH, ed. Understanding G Protein-Coupled Receptors and Their Role in the CNS. 1st ed. New York: Oxford University Press, 2002, pp. 205–220.
81. Fukami K. Structure, regulation, and function of phospholipase C isozymes. J Biochem (Tokyo) 2002;131:293–299.
82. Lopez I, Mak EC, Ding J, Hamm HE, Lomasney JW. A novel bifunctional phospholipase c that is regulated by Galpha 12 and stimulates the Ras/mitogen-activated protein kinase pathway. J Biol Chem 2001;276:2758–2765.
83. Wing MR, Houston D, Kelley GG, Der CJ, Siderovski DP, Harden TK. Activation of phospholipase C-epsilon by heterotrimeric G protein betagammasubunits. J Biol Chem 2001;276:48,257–48,261.
84. Kelley GG, Reks SE, Smrcka AV. Hormonal regulation of phospholipase Cepsilon through distinct and overlapping pathways involving G12 and Ras family G proteins. Biochem J 2004;378:129–139.
85. Song C, Hu CD, Masago M, et al. Regulation of a novel human phospholipase C, PLCepsilon, through membrane targeting by Ras. J Biol Chem 2001;276:2752–2757.
86. Kelley GG, Reks SE, Ondrako JM, Smrcka AV. Phospholipase C(epsilon): a novel Ras effector. EMBO J 2001;20:743–754.
87. Sadja R, Alagem N, Reuveny E. Gating of GIRK channels: details of an intricate, membrane-delimited signaling complex. Neuron 2003;39:9–12.
88. Mirshahi T, Jin T, Logothetis DE. G beta gamma and KACh: old story, new insights. Sci STKE 2003;2003(194):E32.
89. Kaneko S, Akaike A, Satoh M. Receptor-mediated modulation of voltagedependent Ca2+ channels via heterotrimeric G-proteins in neurons. Jpn J Pharmacol 1999;81:324–331.
90. Ikeda SR. Voltage-dependent modulation of N-type calcium channels by G protein beta gamma subunits. Nature 1996;380:255–258.
91. Herlitze S, Garcia DE, Mackie K, Hille B, Scheuer T, Catterall WA. Modulation of Ca2+ channels by G-protein beta gamma subunits. Nature 1996;380:258–262.
92. Zhong J, Hume JR, Keef KD. beta-Adrenergic receptor stimulation of L-type Ca2+ channels in rabbit portal vein myocytes involves both alphas and betagamma G protein subunits. J Physiol 2001;531:105–115.
93. Viard P, Macrez N, Mironneau C, Mironneau J. Involvement of both G protein alphas and beta gamma subunits in beta-adrenergic stimulation of vascular L-type Ca(2+) channels. Br J Pharmacol 2001;132:669–676.
94. Mattingly RR, Macara IG. Phosphorylation-dependent activation of the Ras GRF/CDC25Mm exchange factor by muscarinic receptors and G-protein beta gamma subunits. Nature 1996;382:268–272.
95. Kiyono M, Satoh T, Kaziro Y. G protein beta gamma subunit-dependent Racguanine nucleotide exchange activity of Ras-GRF1/CDC25(Mm). Proc Natl Acad Sci USA 1999;96:4826–4831.
96. Pumiglia KM, LeVine H, Haske T, Habib T, Jove R, Decker SJ. A direct interaction between G-protein beta gamma subunits and the Raf-1 protein kinase. J Biol Chem 1995;270:14,251–14,254.
97. Luttrell LM, Hawes BE, van Biesen T, Luttrell DK, Lansing TJ, Lefkowitz RJ. Role of c-Src tyrosine kinase in G protein-coupled receptor-and Gbetagamma subunit-mediated activation of mitogen-activated protein kinases. J Biol Chem 1996;271:19,443–19,450.
98. Kozasa T, Jiang X, Hart MJ, et al. p115 RhoGEF, a GTPase activating protein for Galpha12 and Galpha13. Science 1998;280:2109–2111.
99. Hart MJ, Jiang X, Kozasa T, et al. Direct stimulation of the guanine nucleotide exchange activity of p115 RhoGEF by Galpha13. Science 1998;280:2112–2114.
100. Jiang Y, Ma W, Wan Y, Kozasa T, Hattori S, Huang XY. The G protein G alpha12 stimulates Bruton’s tyrosine kinase and a rasGAP through a conserved PH/BM domain. Nature 1998;395:808–813.
101. Ito A, Satoh T, Kaziro Y, Itoh H. G protein beta gamma subunit activates Ras, Raf, and MAP kinase in HEK 293 cells. FEBS Lett 1995;368:183–187.
102. Martegani E, Vanoni M, Zippel R, et al. Cloning by functional complementation of a mouse cDNA encoding a homologue of CDC25, a Saccharomyces cerevisiae RAS activator. EMBO J 1992;11:2151–2157.
103. Shou C, Farnsworth CL, Neel BG, Feig LA. Molecular cloning of cDNAs encoding a guanine-nucleotide-releasing factor for Ras p21. Nature 1992;358:351–354.
104. Fukuhara S, Murga C, Zohar M, Igishi T, Gutkind JS. A novel PDZ domain containing guanine nucleotide exchange factor links heterotrimeric G proteins to Rho. J Biol Chem 1999;274:5868–5879.
105. Fukuhara S, Chikumi H, Gutkind JS. Leukemia-associated Rho guanine nucleotide exchange factor (LARG) links heterotrimeric G proteins of the G(12) family to Rho. FEBS Lett 2000;485:183–188.
106. Mochizuki N, Ohba Y, Kiyokawa E, et al. Activation of the ERK/MAPK pathway by an isoform of rap1GAP associated with G alpha(i). Nature 1999;400:891–894.
107. Tsygankova OM, Feshchenko E, Klein PS, Meinkoth JL. TSH/cAMP and GSK3beta elicit opposing effects on Rap1GAP stability. J Biol Chem 2004;279:5501–5507.
108. Jordan JD, He CJ, Eungdamrong NJ, et al. Cannabinoid receptor induced neurite outgrowth is mediated by Rap1 activation through Galphao/i-triggered proteasomal degradation of Rap1GAPII. J Biol Chem, 2005; in press.
109. Gratacap MP, Payrastre B, Nieswandt B, Offermanns S. Differential regulation of Rho and Rac through heterotrimeric G-proteins and cyclic nucleotides. J Biol Chem 2001;276:47,906–47,913. [Epub Sep 17, 2001.]
110. Usui I, Imamura T, Huang J, Satoh H, Olefsky JM. Cdc42 is a Rho GTPase family member that can mediate insulin signaling to glucose transport in 3T3L1 adipocytes. J Biol Chem 2003;278:13,765–13,774.
111. Strittmatter SM, Fishman MC. The neuronal growth cone as a specialized transduction system. Bioessays 1991;13:127–134.
112. Simkowitz P, Ellis L, Pfenninger KH. Membrane proteins of the nerve growth cone and their developmental regulation. J Neurosci 1989;9:1004–1017.
113. Edmonds BT, Moomaw CR, Hsu JT, Slaughter C, Ellis L. The p38 and p34 polypeptides of growth cone particle membranes are the alpha-and beta-subunits of G proteins. Brain Res Dev Brain Res 1990;56:131–136.
114. Strittmatter SM, Vartanian T, Fishman MC. GAP-43 as a plasticity protein in neuronal form and repair. J Neurobiol 1992;23:507–520.
115. Strittmatter SM, Fankhauser C, Huang PL, Mashimo H, Fishman MC. Neuronal pathfinding is abnormal in mice lacking the neuronal growth cone protein GAP-43. Cell 1995;80:445–452.
116. Igarashi M, Strittmatter SM, Vartanian T, Fishman MC. Mediation by G proteins of signals that cause collapse of growth cones. Science 1993;259:77–79.
117. Christofori G. Split personalities: the agonistic antagonist Sprouty. Nat Cell Biol 2003;5:377–379.
118. Dikic I, Giordano S. Negative receptor signalling. Curr Opin Cell Biol 2003;15:128–135.
119. Silva AJ, Kogan JH, Frankland PW, Kida S. CREB and memory. Annu Rev Neurosci 1998;21:127–148.
120. Nestler EJ. Molecular basis of long-term plasticity underlying addiction. Nat Rev Neurosci 2001;2:119–128.