G-protein-coupled receptor signaling, RGS proteins, and lymphocyte function

Critical Reviews in Immunology

Volumn 24, Issue 6, 2004, Pages 409-423

  Kehrl, John H ^a  

^a NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

Author keywords

Cell migration; G proteins; Gene targeting; GPCRs; Lymphocytes; RGS proteins

Indexed keywords

ADRENALIN; CHEMOKINE RECEPTOR CCR3; CHEMOKINE RECEPTOR CCR5; CHEMOKINE RECEPTOR CCR7; CHEMOKINE RECEPTOR CXCR4; COMPLEMENT COMPONENT C5A; G PROTEIN COUPLED RECEPTOR; GUANINE NUCLEOTIDE BINDING PROTEIN; HISTAMINE; LEUKOTRIENE DERIVATIVE; LYMPHOCYTE ANTIGEN RECEPTOR; OPIATE; PHOSPHOLIPID; PROSTAGLANDIN DERIVATIVE; PURINE NUCLEOSIDE; RGS PROTEIN; RGS10 PROTEIN; RGS11 PROTEIN; RGS12 PROTEIN; RGS13 PROTEIN; RGS14 PROTEIN; RGS16 PROTEIN; RGS18 PROTEIN; RGS19 PROTEIN; RGS3 PROTEIN; RGS6 PROTEIN; RGS7 PROTEIN; RGS9 PROTEIN; SEROTONIN; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ANIMAL CELL; HUMAN; HUMAN CELL; HUMAN TISSUE; IMMUNOREGULATION; IMMUNOSTIMULATION; IMMUNOSURVEILLANCE; LYMPHOCYTE FUNCTION; LYMPHOCYTE MIGRATION; MOUSE; NONHUMAN; PRIORITY JOURNAL; RAT; RECEPTOR UPREGULATION; REGULATORY MECHANISM; REVIEW; SIGNAL TRANSDUCTION;

ANIMALS; HUMANS; LYMPHOCYTES; MICE; MODELS, BIOLOGICAL; RECEPTORS, G-PROTEIN-COUPLED; RGS PROTEINS; SIGNAL TRANSDUCTION;

EID: 15444374690     PISSN: 10408401     EISSN: None     Source Type: Journal    
DOI: 10.1615/CritRevImmunol.v24.i6.20     Document Type: Review

References (124)

1. Csete M, Doyle J. Bow ties, metabolism and disease. Trends Biotechnol 2004; 22:446-450.
2. Neer EJ. Heterotrimeric G proteins: Organizers of transmembrane signals. Cell 1995; 80:249-257.
3. Offermanns S, Simon MI. Organization of transmembrane signaling by heterotrimeric G proteins. Cancer Surv 1996; 27:177-198.
4. Hamm HE, Gilchrist A. Heterotrimeric G proteins. Curr Opin Cell Biol 1996; 8:189-196.
5. Kehrl JH. Heterotrimeric G protein signaling: Roles in immune function and fine-tuning by RGS proteins. Immunity 1998; 8:1-10.
6. Ross EM, Wilkie TM. GTPase-activating proteins for heterotrimeric G proteins: Regulators of G protein signaling (RGS) and RGS-like proteins. Annu Rev Biochem 2000; 69:795-827.
7. De Vries L, Zheng B, Fischer T, Elenko E, Farquhar MG. The regulator of G protein signaling family. Annu Rev Pharmacol Toxicol 2000; 40:235-271.
8. Shenoy SK, Lefkowitz RJ. Multifaceted roles of beta-arrestins in the regulation of seven-membrane-spanning receptor trafficking and signaling. Biochem J 2003; 375:503-515.
9. Gilman AG. Nobel Lecture. G proteins and regulation of adenylyl cyclase. Biosci Rep 1995; 15:65-97.
10. Tamir A, Granot Y, Isakov N. Inhibition of T lymphocyte activation by cAMP is associated with downregulation of two parallel mitogen-activated protein kinase pathways, the extracellular signal-related kinase and c-Jun N-terminal kinase. J Immunol 1996; 157: 1514-1522.
11. Kohm AP, Sanders VM. Norepinephrine and beta 2-adrenergic receptor stimulation regulate CD4+ T and B lymphocyte function in vitro and in vivo. Pharmacol Rev 2001; 53:487-525.
12. Fedyk ER, Adawi A, Looney RJ, Phipps RP. Regulation of IgE and cytokine production by cAMP: Implications for extrinsic asthma. Clin Immunol Immunopathol 1996; 81:101-113.
13. Ozegbe P, Foey AD, Ahmed S, Williams RO. Impact of cAMP on the T-cell response to type II collagen. Immunology 2004; 111:35-40.
14. Paliogianni F, Kincaid RL, Boumpas DT. Prostaglandin E2 and other cyclic AMP elevating agents inhibit interleukin 2 gene transcription by counteracting calcineurin-dependent pathways. J Exp Med 1993; 178:1813-2817.
15. Roper RL, Ludlow JW, Phipps RP. Prostaglandin E2 inhibits B lymphocyte activation by a cAMP-dependent mechanism: PGE-inducible regulatory proteins. Cell Immunol 1994; 154:296-308.
16. Fedyk ER, Phipps RP. Prostaglandin E2 receptors of the EP2 and EP4 subtypes regulate activation and differentiation of mouse B lymphocytes to IgE-secreting cells. Proc Natl Acad Sci U S A 1996; 93: 10978-10983.
17. Roper RL, Graf B, Phipps RP. Prostaglandin E2 and cAMP promote B lymphocyte class switching to IgG1. Immunol Lett 2002; 84:191-198.
18. Ohta A, Sitkovsky M. Role of G-protein-coupled adenosine receptors in downregulation of inflammation and protection from tissue damage. Nature 2001; 414:916-920.
19. Luther SA, Cyster JG. Chemokines as regulators of T cell differentiation. Nat Immunol 2001; 2:102-107.
20. Spangrude GJ, Braaten BA, Daynes RA. Molecular mechanisms of lymphocyte extravasation. I. Studies of two selective inhibitors of lymphocyte recirculation. J Immunol 1984; 132:354-362.
21. Bargatze RF, Butcher EC. Rapid G protein-regulated activation event involved in lymphocyte binding to high endothelial venules. J Exp Med 1993; 178:367-372.
22. Cyster JG, Goodnow CC. Pertussis toxin inhibits migration of B and T lymphocytes into splenic white pulp cords. J Exp Med 1995; 182:581-586.
23. Huang R, Cioffi J, Berg K, London R, Cidon M, Maayani S, Mayer L. B cell differentiation factor-induced B cell maturation: Regulation via reduction in cAMP. Cell Immunol 1995; 162:49-55.
24. Ramirez R, Carracedo J, Zamzami N, Castedo M, Kroemer G. Pertussis toxin inhibits activation-induced cell death of human thymocytes, pre-B leukemia cells and monocytes. J Exp Med 1994; 180: 1147-1152.
25. Manna PP, Frazier WA. The mechanism of CD47-dependent killing of T cells: Heterotrimeric Gi-dependent inhibition of protein kinase A. J Immunol 2003; 170:3544-3553.
26. Rot A, von Andrian UH. Chemokines in innate and adaptive host defense: Basic chemokinese grammar for immune cells. Annu Rev Immunol 2004; 22:891-928.
27. Moser B, Wolf M, Walz A, Loetscher P. Chemokines: Multiple levels of leukocyte migration control. Trends Immunol 2004; 25:75-84.
28. Neptune ER, Bourne HR. Receptors induce chemotaxis by releasing the betagamma subunit of Gi, not by activating Gq or Gs. Proc Natl Acad Sci U S A 1997; 94:14489-14494.
29. Arai H, Tsou CL, Charo IF. Chemotaxis in a lymphocyte cell line transfected with C-C chemokine receptor 2B: Evidence that directed migration is mediated by betagamma dimers released by activation of Galphai-coupled receptors. Proc Natl Acad Sci U S A 1997; 94:14495-14499.
30. Devreotes P, Janetopoulos C. Eukaryotic chemotaxis: Distinctions between directional sensing and polarization. J Biol Chem 2003; 278:20445-20448.
31. del Pozo MA, Vicente-Manzanares M, Tejedor R, Serrador JM, Sanchez-Madrid F. Rho GTPases control migration and polarization of adhesion molecules and cytoskeletal ERM components in T lymphocytes. Eur J Immunol 1999; 29:3609-3620.
32. Fukui Y, Hashimoto O, Sanui T, Oono T, Koga H, Abe M, Inayoshi A, Noda M, Oike M, Shirai T, Sasazuki T. Haematopoietic cell-specific CDM family protein DOCK2 is essential for lymphocyte migration. Nature 2001; 412:826-831.
33. Reif K, Cyster J. The CDM protein DOCK2 in lymphocyte migration. Trends Cell Biol 2002; 12: 368-373.
34. Sanui T, Inayoshi A, Noda M, Iwata E, Stein JV, Sasazuki T, Fukui Y. DOCK2 regulates Rac activation and cytoskeletal reorganization through interaction with ELMO1. Blood 2003; 102:2948-2950.
35. Grant KR, Harnett W, Milligan G, Harnett MM. Differential G-protein expression during B- and T-cell development. Immunology 1997; 90:564-571.
36. Amatruda TT, 3rd, Steele DA, Slepak VZ, Simon MI. G alpha 16, a G protein alpha subunit specifically expressed in hematopoietic cells. Proc Natl Acad Sci U S A 1991; 88:5587-5591.
37. Mapara MY, Bommert K, Bargou RC, Leng C, Beck C, Ludwig WD, Gierschik P, Dorken B. G protein subunit G alpha 16 expression is restricted to progenitor B cells during human B-cell differentiation. Blood 1995; 85:1836-1842.
38. Fields TA, Casey PJ. Signalling functions and biochemical properties of pertussis toxin-resistant G-proteins. Biochem J 1997; 321 (Pt 3):561-571.
39. Bence K, Ma W, Kozasa T, Huang XY. Direct stimulation of Bruton's tyrosine kinase by G(q)-protein alpha-subunit. Nature 1997; 389:296-299.
40. Shi CS, Kehrl JH. PYK2 links G(q)alpha and G(13)alpha signaling to NF-kappa B activation. J Biol Chem 2001; 276:31845-31850.
41. Nagao M, Yamauchi J, Kaziro Y, Itoh H. Involvement of protein kinase C and Src family tyrosine kinase in Galphaq/11-induced activation of c-Jun N-terminal kinase and p38 mitogen-activated protein kinase. J Biol Chem 1998; 273:22892-22898.
42. Ogden BE, Hill HR. Histamine regulates lymphocyte mitogenic responses through activation of specific H1 and H2 histamine receptors. Immunology 1980; 41:107-114.
43. Jutel M, Watanabe T, Klunker S, Akdis M, Thomet OA, Malolepszy J, Zak-Nejmark T, Koga R, Kobayashi T, Blaser K, Akdis CA. Histamine regulates T-cell and antibody responses by differential expression of H1 and H2 receptors. Nature 2001; 413:420-425.
44. Ma RZ, Gao J, Meeker ND, Fillmore PD, Tung KS, Watanabe T, Zachary JF, Offner H, Blankenhorn EP, Teuscher C. Identification of Bphs, an autoimmune disease locus, as histamine receptor H1. Science 2002; 297:620-623.
45. Mazer B, Domenico J, Sawami H, Gelfand EW. Platelet-activating factor induces an increase in intracellular calcium and expression of regulatory genes in human B lymphoblastoid cells. J Immunol 1991; 146:1914-1920.
46. Niu J, Vaiskunaite R, Suzuki N, Kozasa T, Carr DW, Dulin N, Voyno-Yasenetskaya TA. Interaction of heterotrimeric G13 protein with an A-kinase-anchoring protein 110(AKAP110) mediates cAMP-independent PKA activation. Curr Biol 2001; 11:1686-1690.
47. 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.
48. Shi CS, Sinnarajah S, Cho H, Kozasa T, Kehrl JH. G13alpha-mediated PYK2 activation. PYK2 is a mediator of G13alpha-induced serum response element-dependent transcription. J Biol Chem 2000; 275:24470-24476.
49. Kozasa T, Jiang X, Hart MJ, Sternweis PM, Singer WD, Gilman AG, Bollag G, Sternweis PC. p115 RhoGEF, a GTPase activating protein for Galpha12 and Galpha13. Science 1998; 280:2109-2111.
50. 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.
51. Vaiskunaite R, Adarichev V, Furthmayr H, Kozasa T, Gudkov A, Voyno-Yasenetskaya TA. Conformational activation of radixin by G13 protein alpha subunit. J Biol Chem 2000; 275:26206-26212.
52. Meigs TE, Fields TA, McKee DD, Casey PJ. Interaction of Galpha 12 and Galpha 13 with the cytoplasmic domain of cadherin provides a mechanism for beta-catenin release. Proc Natl Acad Sci U S A 2001; 98:519-524.
53. Kitamura K, Singer WD, Star RA, Muallem S, Miller RT. Induction of inducible nitric-oxide synthase by the heterotrimeric G protein Galpha13. J Biol Chem 1996; 271:7412-7415.
54. Voyno-Yasenetskaya TA, Pace AM, Bourne HR. Mutant alpha subunits of G12 and G13 proteins induce neoplastic transformation of Rat-1 fibroblasts. Oncogene 1994; 9:2559-2565.
55. Xu N, Voyno-Yasenetskaya T, Gutkind JS. Potent transforming activity of the G13 alpha subunit defines a novel family of oncogenes. Biochem Biophys Res Commun 1994; 201:603-609.
56. Girkontaite I, Missy K, Sakk V, Harenberg A, Tedford K, Potzel T, Pfeffer K, Fischer KD. Lsc is required for marginal zone B cells, regulation of lymphocyte motility and immune responses. Nat Immunol 2001; 2:855-862.
57. Guinamard R, Okigaki M, Schlessinger J, Ravetch JV. Absence of marginal zone B cells in Pyk-2-deficient mice defines their role in the humoral response. Nat Immunol 2000; 1:31-36.
58. Graler MH, Grosse R, Kusch A, Kremmer E, Gudermann T, Lipp M. The sphingosine 1-phosphate receptor S1P4 regulates cell shape and motility via coupling to Gi and G12/13. J Cell Biochem 2003; 89:507-519.
59. Kabarowski JH, Feramisco JD, Le LQ, Gu JL, Luoh SW, Simon MI, Witte ON. Direct genetic demonstration of G alpha 13 coupling to the orphan G protein-coupled receptor G2A leading to RhoA-dependent actin rearrangement. Proc Natl Acad Sci U S A 2000; 97:12109-12114.
60. Le LQ, Kabarowski JH, Weng Z, Satterthwaite AB, Harvill ET, Jensen ER, Miller JF, Witte ON. Mice lacking the orphan G protein-coupled receptor G2A develop a late-onset autoimmune syndrome. Immunity 2001; 14:561-571.
61. Kabarowski JH, Zhu K, Le LQ, Witte ON, Xu Y. Lysophosphatidylcholine as a ligand for the immunoregulatory receptor G2A. Science 2001; 293: 702-705.
62. Murakami N, Yokomizo T, Okuno T, Shimizu T. G2A is a proton-sensing G-protein-coupled receptor antagonized by lysophosphatidylcholine. J Biol Chem 2004; 279:42484-42491.
63. Wang JQ, Kon J, Mogi C, Tobo M, Damirin A, Sato K, Komachi M, Malchinkhuu E, Murata N, Kimura T, Kuwabara A, Wakamatsu K, Koizumi H, Uede T, Tsujimoto G, Kurose H, Sato T, Harada A, Misawa N, Tomura H, Okajima F. TDAG8 is a proton-sensing and psychosine-sensitive G-protein-coupled receptor. J Biol Chem 2004; 279:45626-45633.
64. Malone MH, Wang Z, Distelhorst CW. The glucocorticoid-induced gene tdag8 encodes a pro-apoptotic G protein-coupled receptor whose activation promotes glucocorticoid-induced apoptosis. J Biol Chem 2004; 279:52850-52859.
65. Wettschureck N, Moers A, Offermanns S. Mouse models to study G-protein-mediated signaling. Pharmacol & Theraeputics 2004; 101:75-89.
66. Chen CK, Eversole-Cire P, Zhang H, Mancino V, Chen YJ, He W, Wensel TG and Simon MI. Instability of GGL domain-containing RGS proteins in mice lacking the G protein beta-subunit Gbeta5. Proc Natl Acad Sci U S A 2003; 100:6604-6609.
67. Schwindinger WF, Betz KS, Giger KE, Sabol A, Bronson SK, Robishaw JD. Loss of G protein gamma 7 alters behavior and reduces striatal alpha(olf) level and cAMP production. J Biol Chem 2003; 278: 6575-6579.
68. Schwindinger WF, Giger KE, Betz KS, Stauffer AM, Sunderlin EM, Sim-Selley LJ, Selley DE, Bronson SK, Robishaw JD. Mice with deficiency of G protein gamma3 are lean and have seizures. Mol Cell Biol 2004; 24:7758-7768.
69. Dohlman HG, Thorner J. RGS proteins and signaling by heterotrimeric G proteins. J Biol Chem 1997; 272:3871-3874.
70. Koelle MR. A new family of G-protein regulators-the RGS proteins. Curr Opin Cell Biol 1997; 9:143-147.
71. De Vries L, Mousli M, Wurmser A, Farquhar MG. GAIP, a protein that specifically interacts with the trimeric G protein G alpha i3, is a member of a protein family with a highly conserved core domain. Proc Natl Acad Sci U S A 1995; 92:11916-11920.
72. Druey KM, Blumer KJ, Kang VH, Kehrl JH. Inhibition of G-protein-mediated MAP kinase activation by a new mammalian gene family. Nature 1996; 379:742-746.
73. Koelle MR, Horvitz HR. EGL-10 regulates G protein signaling in the C. elegans nervous system and shares a conserved domain with many mammalian proteins. Cell 1996; 84:115-125.
74. Snow BE, Antonio L, Suggs S, Gutstein HB, Siderovski DP. Molecular cloning and expression analysis of rat Rgs12 and Rgs14. Biochem Biophys Res Commun 1997; 233:770-777.
75. Sierra DA, Gilbert DJ, Householder D, Grishin NV, Yu K, Ukidwe P, Barker SA, He W, Wensel TG, Otero G, Brown G, Copeland NG, Jenkins NA, Wilkie TM. Evolution of the regulators of G-protein signaling multigene family in mouse and human. Genomics 2002; 79:177-185.
76. Berman DM, Wilkie TM and Gilman AG. GAIP and RGS4 are GTPase-activating proteins for the Gi subfamily of G protein alpha subunits. Cell 1996; 86:445-452.
77. Watson N, Linder ME, Druey KM, Kehrl JH, Blumer KJ. RGS family members: GTPase-activating proteins for heterotrimeric G-protein alpha-subunits. Nature 1996; 383:172-175.
78. Hunt TW, Fields TA, Casey PJ, Peralta EG. RGS10 is a selective activator of G alpha i GTPase activity. Nature 1996; 383:175-177.
79. Berman DM, Kozasa T, Gilman AG. The GTPase-activating protein RGS4 stabilizes the transition state for nucleotide hydrolysis. J Biol Chem 1996; 271:27209-27212.
80. Dohlman HG, Song J, Ma D, Courchesne WE, Thorner J. Sst2, a negative regulator of pheromone signaling in the yeast Saccharomyces cerevisiae: Expression, localization, and genetic interaction and physical association with Gpa1 (the G-protein alpha subunit). Mol Cell Biol 1996; 16:5194-5209.
81. Chen CK, Wieland T, Simon MI. RGS-r, a retinal specific RGS protein, binds an intermediate conformation of transducin and enhances recycling. Proc Natl Acad Sci U S A 1996; 93:12885-12889.
82. Neill JD, Duck LW, Sellers JC, Musgrove LC, Scheschonka A, Druey KM, Kehrl JH. Potential role for a regulator of G protein signaling (RGS3) in gonadotropin-releasing hormone (GnRH) stimulated desensitization. Endocrinology 1997; 138:843-846.
83. Hepler JR, Berman DM, Gilman AG, Kozasa T. RGS4 and GAIP are GTPase-activating proteins for Gq alpha and block activation of phospholipase C beta by gamma-thio-GTP-Gq alpha. Proc Natl Acad Sci U S A 1997; 94:428-432.
84. Huang C, Hepler JR, Gilman AG, Mumby SM. Attenuation of Gi- and Gq-mediated signaling by expression of RGS4 or GAIP in mammalian cells. Proc Natl Acad Sci U S A 1997; 94:6159-6163.
85. Coleman DE, Berghuis AM, Lee E, Linder ME, Gilman AG, Sprang SR. Structures of active conformations of Gi alpha 1 and the mechanism of GTP hydrolysis. Science 1994; 265:1405-1412.
86. Tesmer JJ, Berman DM, Gilman AG, Sprang SR. Structure of RGS4 bound to AlF4-activated G(i alpha1): stabilization of the transition state for GTP hydrolysis. Cell 1997; 89:251-261.
87. Hollinger S, Hepler JR. Cellular regulation of RGS proteins: modulators and integrators of G protein signaling. Pharmacol Rev 2002; 54:527-559.
88. Tovey SC, Willars GB. Single-cell imaging of intracellular Ca2+ and phospholipase C activity reveals that RGS 2,3 and 4 differentially regulate signaling via the G{alpha}q/11-linked muscarinic M3 receptor. Mol Pharmacol 2004; 66:1453-1464.
89. Dohlman HG. G proteins and pheromone signaling. Annu Rev Physiol 2002; 64:129-152.
90. Hao N, Yildirim N, Wang Y, Elston TC, Dohlman HG. Regulators of G protein signaling and transient activation of signaling: Experimental and computational analysis reveals negative and positive feedback controls on G protein activity. J Biol Chem 2003; 278:46506-46515.
91. Shi GX, Harrison K, Wilson GL, Moratz C, Kehrl JH. RGS13 regulates germinal center B lymphocytes responsiveness to CXC chemokine ligand (CXCL)12 and CXCL13. J Immunol 2002; 169:2507-2515.
92. Reif K, Cyster JG. RGS molecule expression in murine B lymphocytes and ability to down-regulate chemotaxis to lymphoid chemokines. J Immunol 2000; 164:4720-479
93. Tosetti P, Pathak N, Jacob MH, Dunlap K. RGS3 mediates a calcium-dependent termination of G protein signaling in sensory neurons. Proc Natl Acad Sci U S A 2003; 100:7337-7342.
94. Traver S, Bidot C, Spassky N, Baltauss T, De Tand MF, Thomas JL, Zalc B, Janoueix-Lerosey I, Gunzburg JD. RGS14 is a novel Rap effector that preferentially regulates the GTPase activity of galphao. Biochem J 2000; 350 Pt 1:19-29.
95. Martin-McCaffrey L, Willard FS, Oliveira-Dos-Santos AJ, Natale DR, Snow BE, Kimple RJ, Pajak A, Watson AJ, Dagnino L, Penninger JM, Siderovski DP, D'Souza SJ. RGS14 is a mitotic spindle protein essential from the first division of the mammalian zygote. Dev Cell 2004; 7:763-769.
96. Cho H, Kim DU, Kehrl JH. RGS14 is a centrosomal and nuclear-cytoplasmic shuttling protein that traffics to PML nuclear bodies following heat shock. J Biol Chem 2005; 280:805-814.
97. Chen CK, Burns ME, He W, Wensel TG, Baylor DA, Simon MI. Slowed recovery of rod photoresponse in mice lacking the GTPase accelerating protein RGS9-1. Nature 2000; 403:557-560.
98. Nishiguchi KM, Sandberg MA, Kooijman AC, Martemyanov KA, Pott JW, Hagstrom SA, Arshavsky VY, Berson EL, Dryja TP. Defects in RGS9 or its anchor protein R9AP in patients with slow photoreceptor deactivation. Nature 2004; 427:75-78.
99. -/- mice. Mol Cell Biol 2004; 24:5767-5775.
100. Oliveira-Dos-Santos AJ, Matsumoto G, Snow BE, Bai D, Houston FP, Whishaw IQ, Mariathasan S, Sasaki T, Wakeham A, Ohashi PS, Roder JC, Barnes CA, Siderovski DP, Penninger JM. Regulation of T cell activation, anxiety, and male aggression by RGS2. Proc Natl Acad Sci U S A 2000; 97:12272-12277.
101. Heximer SP, Knutsen RH, Sun X, Kaltenbronn KM, Rhee MH, Peng N, Oliveira-dos-Santos A, Penninger JM, Muslin AJ, Steinberg TH, Wyss JM, Mecham RP, Blumer KJ. Hypertension and prolonged vasoconstrictor signaling in RGS2-deficient mice. J Clin Invest 2003; 111:445-452.
102. Lippert E, Yowe DL, Gonzalo JA, Justice JP, Webster JM, Fedyk ER, Hodge M, Miller C, Gutierrez-Ramos JC, Borrego F, Keane-Myers A, Druey KM. Role of regulator of G protein signaling 16 in inflammation-induced T lymphocyte migration and activation. J Immunol 2003; 171:1542-1555.
103. Su AI, Cooke MP, Ching KA, Hakak Y, Walker JR, Wiltshire T, Orth AP, Vega RG, Sapinoso LM, Moqrich A, Patapoutian A, Hampton GM, Schultz PG, Hogenesch JB. Large-scale analysis of the human and mouse transcriptomes. Proc Natl Acad Sci U S A 2002; 99:4465-4470.
104. Yu S, Yu D, Lee E, Eckhaus M, Lee R, Corria Z, Accili D, Westphal H, Weinstein LS. Variable and tissue-specific hormone resistance in heterotrimeric Gs protein alpha-subunit (Gsalpha) knockout mice is due to tissue-specific imprinting of the Gsalpha gene. Proc Natl Acad Sci U S A 1998; 95:8715-8720.
105. Belluscio L, Gold GH, Nemes A, Axel R. Mice deficient in G(olf) are anosmic. Neuron 1998; 20:69-81.
106. Rudolph U, Finegold MJ, Rich SS, Harriman GR, Srinivasan Y, Brabet P, Boulay G, Bradley A, Birnbaumer L. Ulcerative colitis and adenocarcinoma of the colon in G alpha i2-deficient mice. Nat Genet 1995; 10:143-150.
107. Hornquist CE, Lu X, Rogers-Fani PM, Rudolph U, Shappell S, Birnbaumer L, Harriman GR. G(alpha)i2-deficient mice with colitis exhibit a local increase in memory CD4+ T cells and proinflammatory Th1-type cytokines. J Immunol 1997; 158:1068-1077.
108. He J, Gurunathan S, Iwasaki A, Ash-Shaheed B, Kelsall BL. Primary role for Gi protein signaling in the regulation of interleukin 12 production and the induction of T helper cell type 1 responses. J Exp Med 2000; 191:1605-1610.
109. Dalwadi H, Wei B, Schrage M, Spicher K, Su TT, Birnbaumer L, Rawlings DJ, Braun J. B cell developmental requirement for the G alpha i2 gene. J Immunol 2003; 170:1707-1715.
110. Huang TT, Zong Y, Dalwadi H, Chung C, Miceli MC, Spicher K, Birnbaumer L, Braun J, Aranda R. 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.
111. Jiang M, Gold MS, Boulay G, Spicher K, Peyton M, Brabet P, Srinivasan Y, Rudolph U, Ellison G, Birnbaumer L. Multiple neurological abnormalities in mice deficient in the G protein Go. Proc Natl Acad Sci U S A 1998; 95:3269-3274.
112. Yang J, Wu J, Kowalska MA, Dalvi A, Prevost N, O'Brien PJ, Manning D, Poncz M, Lucki I, Blendy JA, Brass LF. Loss of signaling through the G protein, Gz, results in abnormal platelet activation and altered responses to psychoactive drugs. Proc Natl Acad Sci U S A 2000; 97:9984-9989.
113. Hendry IA, Kelleher KL, Bartlett SE, Leck KJ, Reynolds AJ, Heydon K, Mellick A, Megirian D, Matthaei KI. Hypertolerance to morphine in G(z alpha)-deficient mice. Brain Res 2000; 870:10-19.
114. Calvert PD, Krasnoperova NV, Lyubarsky AL, Isayama T, Nicolo M, Kosaras B, Wong G, Gannon KS, Margolskee RF, Sidman RL, Pugh EN Jr, Makino CL, Lem J. Phototransduction in transgenic mice after targeted deletion of the rod transducin alpha -subunit. Proc Natl Acad Sci U S A 2000; 97:13913-13918.
115. Wong GT, Gannon KS, Margolskee RF. Transduction of bitter and sweet taste by gustducin. Nature 1996; 381:796-800.
116. He W, Margolskee RF, Damak S. Signal transduction of umami taste by gustducin and transducin. Chem Senses 2002; 27:662 (Abstract).
117. Ruiz C, Delay E, Margolskee RF, Kinnamon SC. Behavioral evidence for a role of gustducin in umami taste. Chem Senses 2002; 27:670 (Abstract).
118. Offermanns S, Hashimoto K, Watanabe M, Sun W, Kurihara H, Thompson RF, Inoue Y, Kano M, Simon MI. Impaired motor coordination and persistent multiple climbing fiber innervation of cerebellar Purkinje cells in mice lacking Galphaq. Proc Natl Acad Sci U S A 1997; 94:14089-14094.
119. Offermanns S, Toombs CF, Hu YH, Simon MI. Defective platelet activation in G alpha(q)-deficient mice. Nature 1997; 389:183-186.
120. Offermanns S, Zhao LP, Gohla A, Sarosi I, Simon MI, Wilkie TM. Embryonic cardiomyocyte hypoplasia and craniofacial defects in G alpha q/G alpha 11-mutant mice. EMBO J 1998; 17:4304-4312.
121. Davignon I, Catalina MD, Smith D, Montgomery K, Swamtek J, Croy J, Siegelman M, Wilkie TM. Normal hematopoiesis and inflammatory responses despite discrete signaling defects in Galpha15 knockout mice. Mol Cell Biol 2000; 20:797-804.
122. Gu JL, Muller S, Mancino V, Offermanns S, Simon MI. Interaction of G alpha(12) with G alpha(13) and G alpha(q) signaling pathways. Proc Natl Acad Sci U S A 2002; 99:9352-9357.
123. Offermanns S, Mancino V, Revel JP and Simon MI. Vascular system defects and impaired cell chemokinesis as a result of Galpha13 deficiency. Science 1997; 275:533-536.
124. Moers A, Nieswandt B, Massberg S, Wettschureck N, Gruner S, Konrad I, Schulte V, Aktas B, Gratacap MP, Simon MI, Gawaz M, Offermanns S. G13 is an essential mediator of platelet activation in hemostasis and thrombosis. Nat Med 2003; 9: 1418-1422.