Skip to main content
SpringerLink
Log in

Activation of heterotrimeric G-proteins independent of a G-protein coupled receptor and the implications for signal processing

  • Original Article
  • Published:
Reviews of Physiology, Biochemistry and Pharmacology

Abstract

Heterotrimeric G-proteins are key transducers for signal transfer from outside the cell, mediating signals emanating from cell-surface G-protein coupled receptors (GPCR). Many, if not all, subtypes of heterotrimeric G-proteins are also regulated by accessory proteins that influence guanine nucleotide binding, guanosine triphosphate (GTP) hydrolysis, or subunit interactions. One subgroup of such accessory proteins (activators of G-protein signaling; AGS proteins) refer to a functionally defined group of proteins that activate selected G-protein signaling systems in the absence of classical G-protein coupled receptors. AGS and related proteins provide unexpected insights into the regulation of the G-protein activation–deactivation cycle. Different AGS proteins function as guanine nucleotide exchange factors or guanine nucleotide dissociation inhibitors and may also influence subunit interactions by interaction with Gβγ. These proteins play important roles in the generation or positioning of signaling complexes and of the regulation of GPCR signaling, and as alternative binding partners for G-protein subunits. Perhaps of even broader impact is the discovery that AGS proteins provide a foundation for the concept that heterotrimeric G-protein subunits are processing signals within the cell involving intrinsic cues that do not involve the classical signal input from a cell surface GPCR.

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

Access this article

Log in via an institution
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

Abbreviations

AGS:

Activator of G-protein signaling

ER:

Endoplasmic reticulum

ERK:

Extracellular signal-regulated kinase

GAP:

GTPase-activating protein

GDI:

Guanine nucleotide dissociation inhibitor

GEF:

Guanine nucleotide exchange factor

GPCR:

G-protein coupled receptor

GPR:

G-protein regulatory

GPSM:

G-protein signaling modulator

GTPγS:

Guanosine 5′-3-O-(thio)triphosphate

MHC:

Major histocompatibility complex

NMDA:

N-methyl-D-aspartate

nNOS:

Neuronal nitric oxide synthase

PDZ:

PSD95/DLG/ZO-1 domain

PI3K:

Phosphatidylinositol-3 kinase

PLC:

Phospholipase C

PTB:

Phosphotyrosine binding

RBD:

Ras binding domain

RGS:

Regulator of G-protein signaling

TPR:

Tetratricopeptide repeat

References

  • Abba MC, Drake JA, Hawkins KA, Hu Y, Sun H, Notcovich C, Gaddis S, Sahin A, Baggerly K, Aldaz CM (2004) Transcriptomic changes in human breast cancer progression as determined by serial analysis of gene expression. Breast Cancer Res 6:R499–R513

    Article  PubMed  Google Scholar 

  • Adhikari A, Sprang SR (2003) Thermodynamic characterization of the binding of activator of G protein signaling 3 (AGS3) and peptides derived from AGS3 with G alpha i1. J Biol Chem 278:51825–51832

    Article  PubMed  Google Scholar 

  • Afshar K, Willard FS, Colombo K, Johnston CA, McCudden CR, Siderovski DP, Gonczy P (2004) RIC-8 is required for GPR-1/2-dependent Galpha function during asymmetric division of C. elegans embryos. Cell 119:219–230

    Article  PubMed  Google Scholar 

  • Agell N, Bachs O, Rocamora N, Villalonga P (2002) Modulation of the Ras/Raf/MEK/ERK pathway by Ca(2+), and calmodulin. Cell Signal 14:649–654

    Article  PubMed  Google Scholar 

  • Ahnert-Hilger G, Schafer T, Spicher K, Grund C, Schultz G, Wiedenmann B (1994) Detection of G-protein heterotrimers on large dense core and small synaptic vesicles of neuroendocrine and neuronal cells. Eur J Cell Biol 65:26–38

    PubMed  Google Scholar 

  • Ahringer J (2003) Control of cell polarity and mitotic spindle positioning in animal cells. Curr Opin Cell Biol 15:73–81

    Article  PubMed  Google Scholar 

  • Aronin N, DiFiglia M (1992) The subcellular localization of the G-protein Gi alpha in the basal ganglia reveals its potential role in both signal transduction and vesicle trafficking. J Neurosci 12:3435–3444

    PubMed  Google Scholar 

  • Barbacid M (1987) Ras genes. Annu Rev Biochem 56:779–827

    Article  PubMed  Google Scholar 

  • Bellaiche Y, Radovic A, Woods DF, Hough CD, Parmentier ML, O’Kane CJ, Bryant PJ, Schweisguth F (2001) The Partner of Inscuteable/Discs-large complex is required to establish planar polarity during asymmetric cell division in Drosophila. Cell 106:355–366

    Article  PubMed  Google Scholar 

  • Berman DM, Gilman AG (1998) Mammalian RGS proteins: barbarians at the gate. J Biol Chem 273:1269–1272

    Article  PubMed  Google Scholar 

  • Bernard ML, Peterson YK, Chung P, Jourdan J, Lanier SM (2001) Selective interaction of AGS3 with G-proteins and the influence of AGS3 on the activation state of G-proteins. J Biol Chem 276:1585–1593

    Article  PubMed  Google Scholar 

  • Blackmer T, Larsen EC, Takahashi M, Martin TF, Alford S, Hamm HE (2001) G protein betagamma subunit-mediated presynaptic inhibition: regulation of exocytotic fusion downstream of Ca2+ entry. Science 292:293–297

    Article  PubMed  Google Scholar 

  • Blatch GL, Lassle M (1999) The tetratricopeptide repeat: a structural motif mediating protein-protein interactions. Bioessays 21:932–939

    Article  PubMed  Google Scholar 

  • Blumer JB, Lanier SM (2003) Accessory proteins for G protein-signaling systems: activators of G protein signaling and other nonreceptor proteins influencing the activation state of G proteins. Receptors Channels 9: 195–204

    Article  PubMed  Google Scholar 

  • Blumer JB, Chandler LJ, Lanier SM (2002) Expression analysis and subcellular distribution of the two G-protein regulators AGS3 and LGN indicate distinct functionality. Localization of LGN to the midbody during cytokinesis. J Biol Chem 277:15897–15903

    Article  PubMed  Google Scholar 

  • Blumer JB, Bernard ML, Peterson YK, Nezu J, Chung P, Dunican DJ, Knoblich JA, Lanier SM (2003) Interaction of activator of G-protein signaling 3 (AGS3) with LKB1, a serine/threonine kinase involved in cell polarity and cell cycle progression: phosphorylation of the G-protein regulatory (GPR) motif as a regulatory mechanism for the interaction of GPR motifs with Gi alpha. J Biol Chem 278:23217–23220

    Article  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  • Bonacci TM, Ghosh M, Malik S, Smrcka AV (2005) Regulatory interactions between the amino terminus of G-protein betagamma subunits and the catalytic domain of phospholipase Cbeta2. J Biol Chem 280:10174–10181

    Article  PubMed  Google Scholar 

  • Bowers MS, McFarland K, Lake RW, Peterson YK, Lapish CC, Gregory ML, Lanier SM, Kalivas PW (2004) Activator of G protein signaling 3: a gatekeeper of cocaine sensitization and drug seeking. Neuron 42:269–281

    Article  PubMed  Google Scholar 

  • Brogan MD, Behrend EN, Kemppainen RJ (2001) Regulation of Dexras1 expression by endogenous steroids. Neuroendocrinology 74:244–250

    Article  PubMed  Google Scholar 

  • Bueb JL, Mousli M, Bronner C, Rouot B, Landry Y (1990) Activation of Gi-like proteins, a receptor-independent effect of kinins in mast cells. Mol Pharmacol 38:816–822

    PubMed  Google Scholar 

  • Burde R, Dippel E, Seifert R (1996) Receptor-independent G protein activation may account for the stimulatory effects of first-generation H1-receptor antagonists in HL-60 cells, basophils, and mast cells. Biochem Pharmacol 51:125–131

    Article  PubMed  Google Scholar 

  • Burstein ES, Spalding TA, Brann MR (1998) Structure/function relationships of a G-protein coupling pocket formed by the third intracellular loop of the m5 muscarinic receptor. Biochemistry 37:4052–4058

    Article  PubMed  Google Scholar 

  • Campbell KS, Cooper S, Dessing M, Yates S, Buder A (1998) Interaction of p59fyn kinase with the dynein light chain, Tctex-1, and colocalization during cytokinesis. J Immunol 161:1728–1737

    PubMed  Google Scholar 

  • Cao X, Cismowski MJ, Sato M, Blumer JB, Lanier SM (2004) Identification and characterization of AGS4: a protein containing three G-protein regulatory motifs that regulate the activation state of Gialpha. J Biol Chem 279:27567–27574

    Article  PubMed  Google Scholar 

  • Chandler LJ, Sutton G, Dorairaj NR, Norwood D (2001) N-methyl D-aspartate receptor-mediated bidirectional control of extracellular signal-regulated kinase activity in cortical neuronal cultures. J Biol Chem 276:2627–2636

    Article  PubMed  Google Scholar 

  • Chatterjee TK, Fisher RA (2000a) Cytoplasmic, nuclear, and golgi localization of RGS proteins. Evidence for N-terminal and RGS domain sequences as intracellular targeting motifs. J Biol Chem 275:24013–24021

    Article  PubMed  Google Scholar 

  • Chatterjee TK, Fisher RA (2000b) Novel alternative splicing and nuclear localization of human RGS12 gene products. J Biol Chem 275:29660–29671

    Article  PubMed  Google Scholar 

  • Cheng HY, Obrietan K, Cain SW, Lee BY, Agostino PV, Joza NA, Harrington ME, Ralph MR, Penninger JM (2004) Dexras1 potentiates photic and suppresses nonphotic responses of the circadian clock. Neuron 43:715–728

    Article  PubMed  Google Scholar 

  • Cho H, Kozasa T, Takekoshi K, De Gunzburg J, Kehrl JH (2000) RGS14, a GTPase-activating protein for Gialpha, attenuates Gialpha- and G13alpha-mediated signaling pathways. Mol Pharmacol 58:569–576

    PubMed  Google Scholar 

  • Cho H, Kim DU, Kehrl JH (2005) RGS14 is a centrosomal and nuclear cytoplasmic shuttling protein that traffics to promyelocytic leukemia nuclear bodies following heat shock. J Biol Chem 280:805–814

    PubMed  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • Cismowski MJ, Ma C, Ribas C, Xie X, Spruyt M, Lizano JS, Lanier SM, Duzic E (2000) Activation of heterotrimeric G-protein signaling by a ras-related protein: implications for signal integration. J Biol Chem 275:23421–23424

    Article  PubMed  Google Scholar 

  • Cismowski MJ, Takesono A, Ma C, Lanier SM, Duzic E (2002) Identification of modulators of mammalian G-protein signaling by functional screens in the yeast Saccharomyces cerevisiae. Methods Enzymol 344:153–168

    PubMed  Google Scholar 

  • Colombo K, Grill SW, Kimple RJ, Willard FS, Siderovski DP, Gonczy P (2003) Translation of polarity cues into asymmetric spindle positioning in Caenorhabditis elegans embryos. Science 300:1957–1961

    Article  PubMed  Google Scholar 

  • Couwenbergs C, Spilker AC, Gotta M (2004) Control of embryonic spindle positioning and Galpha activity by C. elegans RIC-8. Curr Biol 14:1871–1876

    Article  PubMed  Google Scholar 

  • Cox AD, Der CJ (2003) The dark side of ras: regulation of apoptosis. Oncogene 22:8999–9006

    Article  PubMed  Google Scholar 

  • Crouch MF, Simson L (1997) The G-protein G(I) regulates mitosis but not DNA synthesis in growth factor-activated fibroblasts: a role for the nuclear translocation of G(I). FASEB J 11:189–198

    PubMed  Google Scholar 

  • Crouch MF, Osborne GW, Willard FS (2000) The GTP-binding protein G(ialpha) translocates to kinetochores and regulates the M-G(1) cell cycle transition of Swiss 3T3 cells. Cell Signal 12:153–163

    Article  PubMed  Google Scholar 

  • D’Andrea LD, Regan L (2003) TPR proteins: the versatile helix. Trends Biochem Sci 28:655–662

    Article  PubMed  Google Scholar 

  • Denker SP, McCaffery JM, Palade GE, Insel PA, Farquhar MG (1996) Differential distribution of alpha subunits and beta gamma subunits of heterotrimeric G proteins on Golgi membranes of the exocrine pancreas. J Cell Biol 133:1027–1040

    Article  PubMed  Google Scholar 

  • Detert H, Seifert R, Schunack W (1996) Cationic amphiphiles with G-protein-stimulatory activity: studies on the role of the basic domain in the activation process. Pharmazie 51:67–72

    PubMed  Google Scholar 

  • DeVries L, Farquhar MG (1999) RGS proteins: more than just GAPs for heterotrimeric G proteins. Trends Cell Biol 9:138–144

    Article  PubMed  Google Scholar 

  • DeVries 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 Galpha I subunits. Proc Natl Acad Sci USA 97:14364–14369

    Article  PubMed  Google Scholar 

  • Dohlman HG, Thorner J (1997) RGS proteins and signaling by heterotrimeric G proteins. J Biol Chem 272:3871–3874

    Article  PubMed  Google Scholar 

  • Du Q, Macara IG (2004) Mammalian Pins is a conformational switch that links NuMA to heterotrimeric G proteins. Cell 119:503–516

    Article  PubMed  Google Scholar 

  • Du Q, Stukenberg PT, Macara IG (2001) A mammalian partner of inscuteable binds NuMA and regulates mitotic spindle organization. Nat Cell Biol 3:1069–1075

    Article  PubMed  Google Scholar 

  • Duzic E, Lanier SM (1992) Factors determining the specificity of signal transduction by guanine nucleotide-binding protein-coupled receptors. III. Coupling of alpha 2-adrenergic receptor subtypes in a cell type-specific manner. J Biol Chem 267:24045–24052

    PubMed  Google Scholar 

  • Falk JD, Vargiu P, Foye PE, Usui H, Perez J, Danielson PE, Lerner DL, Bernal J, Sutcliffe JG (1999) Rhes: a striatal-specific Ras homolog related to Dexras1. J Neurosci Res 57:782–788

    Article  PubMed  Google Scholar 

  • Fang M, Jaffrey SR, Sawa A, Ye K, Luo X, Snyder SH (2000) Dexras1: a G protein specifically coupled to neuronal nitric oxide synthase via CAPON. Neuron 28:183–193

    Article  PubMed  Google Scholar 

  • Feig LA, Cooper GM (1988) Relationship among guanine nucleotide exchange, GTP hydrolysis, and transforming potential of mutated ras proteins. Mol Cell Biol 8:2472–2478

    PubMed  Google Scholar 

  • Fiordalisi JJ, Holly SP, Johnson RL II, Parise LV, Cox AD (2002) A distinct class of dominant negative Ras mutants: cytosolic GTP-bound Ras effector domain mutants that inhibit Ras signaling and transformation and enhance cell adhesion. J Biol Chem 277:10813–10823

    Article  PubMed  Google Scholar 

  • Franzoni L, Nicastro G, Pertinhez TA, Oliveira E, Nakaie CR, Paiva AC, Schreier S, Spisni A (1999) Structure of two fragments of the third cytoplasmic loop of the rat angiotensin II AT1A receptor: implications with respect to receptor activation and G-protein selection and coupling. J Biol Chem 274:227–235

    Article  PubMed  Google Scholar 

  • Freissmuth M, Waldhoer M, Bofill-Cardona E, Nanoff C (1999) G protein antagonists. Trends Pharmacol Sci 20:237–245

    Article  PubMed  Google Scholar 

  • Gaetz J, Kapoor TM (2004) Dynein/dynactin regulate metaphase spindle length by targeting depolymerizing activities to spindle poles. J Cell Biol 166:465–471

    Article  PubMed  Google Scholar 

  • Ghosh M, Peterson YK, Lanier SM, Smrcka AV (2003) Receptor and nucleotide independent mechanisms for promoting G-protein subunit dissociation. J Biol Chem 278:34747–34750

    Article  PubMed  Google Scholar 

  • Gotta M, Dong Y, Peterson YK, Lanier SM, Ahringer J (2003) Asymmetrically distributed C. elegans homologs of AGS3/PINS control spindle position in the early embryo. Curr Biol 13:1029–1037

    Article  PubMed  Google Scholar 

  • Goubaeva F, Ghosh M, Malik S, Yang J, Hinkle PM, Griendling KK, Neubig RR, Smrcka AV (2003) Stimulation of cellular signaling and G protein subunit dissociation by G protein betagamma subunit-binding peptides. J Biol Chem 278:19634–19641

    Article  PubMed  Google Scholar 

  • Graham TE, Key TA, Kilpatrick K, Dorin RI (2001) Dexras1/AGS-1, a steroid hormone-induced guanosine triphosphate-binding protein, inhibits 3’,5’-cyclic adenosine monophosphate-stimulated secretion in AtT-20 corticotroph cells. Endocrinology 142:2631–2640

    Article  PubMed  Google Scholar 

  • Graham TE, Prossnitz ER, Dorin RI (2002) Dexras1/AGS-1 inhibits signal transduction from the Gi-coupled formyl peptide receptor to Erk-1/2 MAP kinases. J Biol Chem 277:10876–10882

    Article  PubMed  Google Scholar 

  • Graham TE, Qiao Z, Dorin RI (2004) Dexras1 inhibits adenylyl cyclase. Biochem Biophys Res Commun 316:307–312

    Article  PubMed  Google Scholar 

  • Harrison A, Olds-Clarke P, King SM (1998) Identification of the t complex-encoded cytoplasmic dynein light chain tctex1 in inner arm I1 supports the involvement of flagellar dyneins in meiotic drive. J Cell Biol 140:1137–1147

    Article  PubMed  Google Scholar 

  • Helms JB (1995) Role of heterotrimeric GTP binding proteins in vesicular protein transport: indications for both classical and alternative G protein cycles. FEBS Lett 369:84–88

    Article  PubMed  Google Scholar 

  • Herrmann C (2003) Ras-effector interactions: after one decade. Curr Opin Struct Biol 13:122–129

    Article  PubMed  Google Scholar 

  • Herrmann C, Horn G, Spaargaren M, Wittinghofer A (1996) Differential interaction of the ras family GTP-binding proteins H-Ras, Rap1A, and R-Ras with the putative effector molecules Raf kinase and Ral-guanine nucleotide exchange factor. J Biol Chem 271:6794–6800

    Article  PubMed  Google Scholar 

  • Herzog H, Hort YJ, Ball HJ, Hayes G, Shine J, Selbie LA (1992) Cloned human neuropeptide Y receptor couples to two different second messenger systems. Proc Natl Acad Sci USA 89:5794–5798

    PubMed  Google Scholar 

  • Hess HA, Roper JC, Grill SW, Koelle MR (2004) RGS-7 completes a receptor-independent heterotrimeric G protein cycle to asymmetrically regulate mitotic spindle positioning in C. elegans. Cell 119:209–218

    Article  PubMed  Google Scholar 

  • Higashijima T, Burnier J, Ross EM (1990) Regulation of Gi and Go by mastoparan, related amphiphilic peptides, and hydrophobic amines: mechanism and structural determinants of activity. J Biol Chem 265:14176–14186

    PubMed  Google Scholar 

  • Hollinger S, Hepler JR (2002) Cellular regulation of RGS proteins: modulators and integrators of G protein signaling. Pharmacol Rev 54:527-559

    Article  PubMed  Google Scholar 

  • Hollinger S, Taylor JB, Goldman EH, Hepler JR (2001) RGS14 is a bifunctional regulator of Galphai/o activity that exists in multiple populations in brain. J Neurochem 79:941–949

    Article  PubMed  Google Scholar 

  • Hollinger S, Ramineni S, Hepler JR (2003) Phosphorylation of RGS14 by protein kinase A potentiates its activity toward G alpha I. Biochemistry 42:811–819

    Article  PubMed  Google Scholar 

  • Hughes JR, Bullock SL, Ish-Horowicz D (2004) Inscuteable mRNA localization is dynein-dependent and regulates apicobasal polarity and spindle length in Drosophila neuroblasts. Curr Biol 14:1950–1956

    Article  PubMed  Google Scholar 

  • Ja WW, Roberts RW (2004) In vitro selection of state-specific peptide modulators of G protein signaling using mRNA display. Biochemistry 43:9265–9275

    Article  PubMed  Google Scholar 

  • Jaffrey SR, Fang M, Snyder SH (2002) Nitrosopeptide mapping: a novel methodology reveals s-nitrosylation of dexras1 on a single cysteine residue. Chem Biol 9:1329–1335

    Article  PubMed  Google Scholar 

  • Jordan JD, Carey KD, Stork PJ, Iyengar R (1999) Modulation of rap activity by direct interaction of Galpha(o) with Rap1 GTPase-activating protein. J Biol Chem 274:21507–21510

    Article  PubMed  Google Scholar 

  • Kaushik R, Yu F, Chia W, Yang X, Bahri S (2003) Subcellular localization of LGN during mitosis: evidence for its cortical localization in mitotic cell culture systems and its requirement for normal cell cycle progression. Mol Biol Cell 14:3144–3155

    Article  PubMed  Google Scholar 

  • Kavelaars A, Jeurissen F, von Frijtag Drabbe Kunzel J, Herman van Roijen J, Rijkers GT, Heijnen CJ (1993) Substance P induces a rise in intracellular calcium concentration in human T lymphocytes in vitro: evidence of a receptor-independent mechanism. J Neuroimmunol 42:61–70

    Article  PubMed  Google Scholar 

  • Kemppainen RJ, Behrend EN (1998) Dexamethasone rapidly induces a novel ras superfamily member-related gene in AtT-20 cells. J Biol Chem 273:3129–3131

    Article  PubMed  Google Scholar 

  • Kemppainen RJ, Cox E, Behrend EN, Brogan MD, Ammons JM (2003) Identification of a glucocorticoid response element in the 3′-flanking region of the human Dexras1 gene. Biochim Biophys Acta 1627:85–89

    PubMed  Google Scholar 

  • Kerov VS, Natochin M, Artemyev NO (2005) Interaction of transducin-alpha with LGN, a G-protein modulator expressed in photoreceptor cells. Mol Cell Neurosci 28:485–495

    Article  PubMed  Google Scholar 

  • Kimple RJ, DeVries L, Tronchere H, Behe CI, Morris RA, Gist Farquhar M, Siderovski DP (2001) RGS12 and RGS14 GoLoco motifs are Galpha(I) interaction sites with guanine nucleotide dissociation inhibitor activity. J Biol Chem 276:29275–29281

    Article  PubMed  Google Scholar 

  • Kimple RJ, Kimple ME, Betts L, Sondek J, Siderovski DP (2002) Structural determinants for GoLoco-induced inhibition of nucleotide release by Galpha subunits. Nature 416:878–881

    Article  PubMed  Google Scholar 

  • Kimple RJ, Willard FS, Hains MD, Jones MB, Nweke GK, Siderovski DP (2004) Guanine nucleotide dissociation inhibitor activity of the triple GoLoco motif protein G18: alanine-to-aspartate mutation restores function to an inactive second GoLoco motif. Biochem J 378:801–808

    Article  PubMed  Google Scholar 

  • Kinoshita-Kawada M, Oberdick J, Xi Zhu M (2004) A Purkinje cell specific GoLoco domain protein, L7/Pcp-2, modulates receptor-mediated inhibition of Cav2.1 Ca2+ channels in a dose-dependent manner. Brain Res Mol Brain Res 132:73–86

    Article  PubMed  Google Scholar 

  • Klein C, Paul JI, Sauve K, Schmidt MM, Arcangeli L, Ransom J, Trueheart J, Manfredi JP, Broach JR, Murphy AJ (1998) Identification of surrogate agonists for the human FPRL-1 receptor by autocrine selection in yeast. Nat Biotechnol 16:1334–1337

    Article  PubMed  Google Scholar 

  • Klinker JF, Seifert R (1997) Morphine and muscle relaxants are receptor-independent G-protein activators and cromolyn is an inhibitor of stimulated G-protein activity. Inflamm Res 46:46–50

    Article  PubMed  Google Scholar 

  • Klinker JF, Seifert R, Damm H, Rommelspacher H (1997) Activation by beta-carbolines of G-proteins in HL-60 membranes and the bovine retinal G-protein transducin in a receptor-independent manner. Biochem Pharmacol 53:1621–1626

    Article  PubMed  Google Scholar 

  • Knoblich JA (2001) Asymmetric cell division during animal development. Nat Rev Mol Cell Biol 2:11–20

    Article  PubMed  Google Scholar 

  • Kroslak T, Koch T, Kahl E, Hollt V (2001) Human phosphatidylethanolamine-binding protein facilitates heterotrimeric G protein-dependent signaling. J Biol Chem 276:39772–39778

    Article  PubMed  Google Scholar 

  • Lankford K, Cypher C, Letourneau P (1990) Nerve growth cone motility. Curr Opin Cell Biol 2:80–85

    PubMed  Google Scholar 

  • Law GJ, Northrop AJ, Mason WT (1993) Rab3-peptide stimulates exocytosis from mast cells via a pertussis toxin-sensitive mechanism. FEBS Lett 333:56–60

    Article  PubMed  Google Scholar 

  • Leschke C, Storm R, Breitweg-Lehmann E, Exner T, Nurnberg B, Schunack W (1997) Alkyl-substituted amino acid amides and analogous di- and triamines: new non-peptide G protein activators. J Med Chem 40:3130–3139

    Article  PubMed  Google Scholar 

  • Lova P, Paganini S, Hirsch E, Barberis L, Wymann M, Sinigaglia F, Balduini C, Torti M (2003) A selective role for phosphatidylinositol 3,4,5-trisphosphate in the Gi-dependent activation of platelet Rap1B. J Biol Chem 278:131–138

    Article  PubMed  Google Scholar 

  • Luo Y, Denker BM (1999) Interaction of heterotrimeric G protein Galphao with Purkinje cell protein-2: evidence for a novel nucleotide exchange factor. J Biol Chem 274:10685–10688

    Article  PubMed  Google Scholar 

  • Maier O, Ehmsen E, Westermann P (1995) Trimeric G protein alpha subunits of the Gs and Gi families localized at the Golgi membrane. Biochem Biophys Res Commun 208:135–143

    Article  PubMed  Google Scholar 

  • Malbon CC (1997) Heterotrimeric G-proteins and development. Biochem Pharmacol 53:1–4

    Article  PubMed  Google Scholar 

  • Marjamaki A, Sato M, Bouet-Alard R, Yang Q, Limon-Boulez I, Legrand C, Lanier SM (1997) Factors determining the specificity of signal transduction by guanine nucleotide-binding protein-coupled receptors. Integration of stimulatory and inhibitory input to the effector adenylyl cyclase. J Biol Chem 272:16466–16473

    Article  PubMed  Google Scholar 

  • Martin ME, Hidalgo J, Vega FM, Velasco A (1999) Trimeric G proteins modulate the dynamic interaction of PKAII with the Golgi complex. J Cell Sci 112:3869–3878

    PubMed  Google Scholar 

  • 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 (2004) RGS14 is a mitotic spindle protein essential from the first division of the mammalian zygote. Dev Cell 7:763–769

    Article  PubMed  Google Scholar 

  • Marty C, Browning DD, Ye RD (2003) Identification of tetratricopeptide repeat 1 as an adaptor protein that interacts with heterotrimeric G proteins and the small GTPase Ras. Mol Cell Biol 23:3847–3858

    Article  PubMed  Google Scholar 

  • McCormick F (1995) Ras-related proteins in signal transduction and growth control. Mol Reprod Dev 42:500–506

    Article  PubMed  Google Scholar 

  • Meng J, Casey PJ (2002) Activation of Gz attenuates Rap1-mediated differentiation of PC12 cells. J Biol Chem 277:43417–43424

    Article  PubMed  Google Scholar 

  • Meng J, Glick JL, Polakis P, Casey PJ (1999) Functional interaction between Galpha(z) and Rap1GAP suggests a novel form of cellular cross-talk. J Biol Chem 274:36663–36669

    Article  PubMed  Google Scholar 

  • Merdes A, Heald R, Samejima K, Earnshaw WC, Cleveland DW (2000) Formation of spindle poles by dynein/dynactin-dependent transport of NuMA. J Cell Biol 149:851–862

    Article  PubMed  Google Scholar 

  • Miller KG, Rand JB (2000) A role for RIC-8 (Synembryn) and GOA-1 (G(o)alpha) in regulating a subset of centrosome movements during early embryogenesis in Caenorhabditis elegans. Genetics 156:1649–1660

    PubMed  Google Scholar 

  • Mittal V, Linder ME (2004) The RGS14 GoLoco domain discriminates among Galphai isoforms. J Biol Chem 279:46772–46778

    Article  PubMed  Google Scholar 

  • Mochizuki N, Cho G, Wen B, Insel PA (1996) Identification and cDNA cloning of a novel human mosaic protein, LGN, based on interaction with G alpha i2. Gene 181:39–43

    Article  PubMed  Google Scholar 

  • Mochizuki N, Ohba Y, Kiyokawa E, Kurata T, Murakami T, Ozaki T, Kitabatake A, Nagashima K, Matsuda M (1999) Activation of the ERK/MAPK pathway by an isoform of rap1GAP associated with G alpha(I). Nature 400:891–894

    Article  PubMed  Google Scholar 

  • Mousli M, Bueb JL, Bronner C, Rouot B, Landry Y (1990) G protein activation: a receptor-independent mode of action for cationic amphiphilic neuropeptides and venom peptides. Trends Pharmacol Sci 11:358–362

    Article  PubMed  Google Scholar 

  • Mueller S, Cao X, Welker R, Wimmer E (2002) Interaction of the poliovirus receptor CD155 with the dynein light chain Tctex-1 and its implication for poliovirus pathogenesis. J Biol Chem 277:7897–7904

    Article  PubMed  Google Scholar 

  • Nagano F, Orita S, Sasaki T, Naito A, Sakaguchi G, Maeda M, Watanabe T, Kominami E, Uchiyama Y, Takai Y (1998) Interaction of Doc2 with tctex-1, a light chain of cytoplasmic dynein. Implication in dynein-dependent vesicle transport. J Biol Chem 273:30065–30068

    Article  PubMed  Google Scholar 

  • Nair KS, Mendez A, Blumer JB, Rosenzweig DH, Slepak VZ (2005) The presence of a Leu-Gly-Asn repeat enriched protein (LGN), a putative binding partner of transducin, in ROD photoreceptors. Invest Ophthalmol Vis Sci 46:383–389

    Article  PubMed  Google Scholar 

  • Nanoff C, Kudlacek O, Freissmuth M (2002) Development of Gs-selective inhibitory compounds. Methods Enzymol 344:469–480

    PubMed  Google Scholar 

  • Natochin M, Lester B, Peterson YK, Bernard ML, Lanier SM, Artemyev NO (2000) AGS3 inhibits GDP dissociation from Gα subunits of Gi family and rhodopsin-dependent activation of transducin. J Biol Chem 275:40981-40985

    Article  PubMed  Google Scholar 

  • Natochin M, Gasimov KG, Artemyev NO (2001) Inhibition of GDP/GTP exchange on G alpha subunits by proteins containing G-protein regulatory motifs. Biochemistry 40:5322–5328

    PubMed  Google Scholar 

  • Ngsee JK, Miller K, Wendland B, Scheller RH (1990) Multiple GTP-binding proteins from cholinergic synaptic vesicles. J Neurosci 10:317–322

    PubMed  Google Scholar 

  • Nurnberg B, Ahnert-Hilger G (1996) Potential roles of heterotrimeric G proteins of the endomembrane system. FEBS Lett 389:61–65

    Article  PubMed  Google Scholar 

  • Ogier-Denis E, Couvineau A, Maoret JJ, Houri JJ, Bauvy C, De Stefanis D, Isidoro C, Laburthe M, Codogno P (1995) A heterotrimeric Gi3-protein controls autophagic sequestration in the human colon cancer cell line HT-29. J Biol Chem 270:13–16

    Article  PubMed  Google Scholar 

  • Ogier-Denis E, Houri JJ, Bauvy C, Codogno P (1996) Guanine nucleotide exchange on heterotrimeric Gi3 protein controls autophagic sequestration in HT-29 cells. J Biol Chem 271:28593–28600

    Article  PubMed  Google Scholar 

  • Ogier-Denis E, Petiot A, Bauvy C, Codogno P (1997) Control of the expression and activity of the Galpha-interacting protein (GAIP) in human intestinal cells. J Biol Chem 272:24599–24603

    Article  PubMed  Google Scholar 

  • Pacold ME, Suire S, Perisic O, Lara-Gonzalez S, Davis CT, Walker EH, Hawkins PT, Stephens L, Eccleston JF, Williams RL (2000) Crystal structure and functional analysis of Ras binding to its effector phosphoinositide 3-kinase gamma. Cell 103:931–943

    Article  PubMed  Google Scholar 

  • Parmentier ML, Woods D, Greig S, Phan PG, Radovic A, Bryant P, O’Kane CJ (2000) Rapsynoid/partner of inscuteable controls asymmetric division of larval neuroblasts in Drosophila. J Neurosci 20:RC84

    PubMed  Google Scholar 

  • Pattingre S, DeVries L, Bauvy C, Chantret I, Cluzeaud F, Ogier-Denis E, Vandewalle A, Codogno P (2003) The G-protein regulator AGS3 controls an early event during macroautophagy in human intestinal HT-29 cells. J Biol Chem 278:20995–21002

    Article  PubMed  Google Scholar 

  • Pattingre S, Petiot A, Codogno P (2004) Analyses of Galpha-interacting protein and activator of G-protein-signaling-3 functions in macroautophagy. Methods Enzymol 390:17–31

    PubMed  Google Scholar 

  • Perez DM, DeYoung MB, Graham RM (1993) Coupling of expressed alpha 1B- and alpha 1D-adrenergic receptor to multiple signaling pathways is both G protein and cell type specific. Mol Pharmacol 44:784–795

    PubMed  Google Scholar 

  • Peterson YK, Bernard ML, Hong Z, Graber SG, Lanier SM (2000) Stabilization of the GDP-bound conformation of Giα by a peptide derived from the G-protein regulatory motif of AGS3. J Biol Chem 275:33193–33196

    Article  PubMed  Google Scholar 

  • Peterson YK, Hazard S III, Graber SG, Lanier SM (2002) Identification of structural features in the G-protein regulatory motif required for regulation of heterotrimeric G-proteins. J Biol Chem 277:6767–6770

    Article  PubMed  Google Scholar 

  • Pinxteren JA, O’Sullivan AJ, Tatham PE, Gomperts BD (1998) Regulation of exocytosis from rat peritoneal mast cells by G protein beta gamma-subunits. EMBO J 17:6210–6218

    Article  PubMed  Google Scholar 

  • Pizzinat N, Takesono A, Lanier SM (2001) Identification of a truncated form of the G-protein regulator AGS3 in heart that lacks the tetratricopeptide repeat domains. J Biol Chem 276:16601–16610

    Article  PubMed  Google Scholar 

  • Repke H, Bienert M (1987) Mast cell activation—a receptor-independent mode of substance P action? FEBS Lett 221:236–240

    Article  PubMed  Google Scholar 

  • Reynolds NK, Schade MA, Miller KG (2005) Convergent, RIC-8-dependent G{alpha} signaling pathways in the caenorhabditis elegans synaptic signaling network. Genetics 169:651–670

    Article  PubMed  Google Scholar 

  • Ribas C, Takesono A, Sato M, Hildebrandt JD, Lanier SM (2002) Pertussis toxin-insensitive activation of the heterotrimeric G-proteins Gi/Go by the NG108-15 G-protein activator. J Biol Chem 277:50223–50225

    Article  PubMed  Google Scholar 

  • Ross EM, Higashijima T (1994) Regulation of G-protein activation by mastoparans and other cationic peptides. Methods Enzymol 237:26–37

    PubMed  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

  • Rupnik M, Law GJ, Mason WT, Zorec R (1997) Mastoparan and Rab3AL peptide potentiation of calcium-independent secretory activity in rat melanotrophs is inhibited by GDPβS. FEBS Lett 411:356–358

    Article  PubMed  Google Scholar 

  • Saraste M, Sibbald PR, Wittinghofer A (1990) The P-loop—a common motif in ATP- and GTP-binding proteins. Trends Biochem Sci 15:430–434

    Article  PubMed  Google Scholar 

  • Sato M, Kataoka R, Dingus J, Wilcox M, Hildebrandt J, Lanier SM (1995) Factors determining specificity of signal transduction by G-protein-coupled receptors. IV. Regulation of signal transfer from receptor to G-protein. J Biol Chem 270:15269–15276

    Article  PubMed  Google Scholar 

  • Sato M, Ribas C, Hildebrandt JD, Lanier SM (1996) Characterization of a G-protein activator in the neuroblastoma-glioma cell hybrid NG108-15. J Biol Chem 271:30052–30060

    Article  PubMed  Google Scholar 

  • Sato M, Gettys TW, Lanier SM (2004) AGS3 and signal integration by Galpha(s)- and Galpha(i)-coupled receptors: AGS3 blocks the sensitization of adenylyl cyclase following prolonged stimulation of a Galpha(i)-coupled receptor by influencing processing of Galpha(i). J Biol Chem 279:13375–13382

    Article  PubMed  Google Scholar 

  • Schade MA, Reynolds NK, Dollins CM, Miller KG (2005) Mutations that rescue the paralysis of caenorhabditis elegans ric-8 (Synembryn) mutants activate the G{alpha}s pathway and define a third major branch of the synaptic signaling network. Genetics 169:631–649

    Article  PubMed  Google Scholar 

  • Schaefer M, Shevchenko A, Shevchenko A, Knoblich JA (2000) A protein complex containing Inscuteable and the Galpha-binding protein Pins orients asymmetric cell divisions in Drosophila. Curr Biol 10:353–362

    Article  PubMed  Google Scholar 

  • Schaefer M, Petronczki M, Dorner D, Forte M, Knoblich JA (2001) Heterotrimeric G proteins direct two modes of asymmetric cell division in the Drosophila nervous system. Cell 107:183–194

    Article  PubMed  Google Scholar 

  • Scott JK, Huang SF, Gangadhar BP, Samoriski GM, Clapp P, Gross RA, Taussig R, Smrcka AV (2001) Evidence that a protein-protein interaction ‘hot spot’ on heterotrimeric G protein betagamma subunits is used for recognition of a subclass of effectors. EMBO J 20:767–776

    Article  PubMed  Google Scholar 

  • Seifert R, Hageluken A, Hoer A, Hoer D, Grunbaum L, Offermanns S, Schwaner I, Zinge V, Schunack W, Schultz G (1994) The H1 receptor agonist 2-(3-chlorophenyl) histamine activates Gi proteins in HL-60 cells through a mechanism that is independent of known histamine receptor subtypes. Mol Pharmacol 45:578–586

    PubMed  Google Scholar 

  • Siderovski DP, Diverse-Pierluissi M, De Vries L (1999) The GoLoco motif: a Galphai/o binding motif and potential guanine-nucleotide exchange factor. Trends Biochem Sci 24:340–341

    Article  PubMed  Google Scholar 

  • Smine A, Xu X, Nishiyama K, Katada T, Gambetti P, Yadav SP, Wu X, Shi YC, Yasuhara S, Homburger V, Okamoto T (1998) Regulation of brain G-protein Go by Alzheimer’s disease gene presenilin-1. J Biol Chem 273:16281–16288

    Article  PubMed  Google Scholar 

  • Snow BE, Hall RA, Krumins AM, Brothers GM, Bouchard D, Brothers CA, Chung S, Mangion J, Gilman AG, Lefkowitz RJ, Siderovski DP (1998) GTPase activating specificity of RGS12 and binding specificity of an alternatively spliced PDZ (PSD-95/Dlg/ZO-1) domain. J Biol Chem 273:17749–17755

    Article  PubMed  Google Scholar 

  • Spicer J, Ashworth A (2004) LKB1 kinase: master and commander of metabolism and polarity. Curr Biol 14:R383–R385

    Article  PubMed  Google Scholar 

  • Srinivasan DG, Fisk RM, Xu H, van den Heuvel S (2003) A complex of LIN-5 and GPR proteins regulates G protein signaling and spindle function in C. elegans. Genes Dev 17:1225–1239

    Article  PubMed  Google Scholar 

  • St Croix B, Rago C, Velculescu V, Traverso G, Romans KE, Montgomery E, Lal A, Riggins GJ, Lengauer C, Vogelstein B, Kinzler KW (2000) Genes expressed in human tumor endothelium. Science 289:1197–1202

    Article  PubMed  Google Scholar 

  • Stow JL, de Almeida JB, Narula N, Holtzman EJ, Ercolani L, Ausiello DA (1991) A heterotrimeric G protein, G alpha i-3, on Golgi membranes regulates the secretion of a heparan sulfate proteoglycan in LLC-PK1 epithelial cells. J Cell Biol 114:1113–1124

    Article  PubMed  Google Scholar 

  • Strader CD, Sigal IS, Dixon RA (1989) Structural basis of beta-adrenergic receptor function. FASEB J 3:1825–1832

    PubMed  Google Scholar 

  • Strittmatter SM, Valenzuela D, Sudo Y, Linder ME, Fishman MC (1991) An intracellular guanine nucleotide release protein for Go. GAP-43 stimulates isolated alpha subunits by a novel mechanism. J Biol Chem 266:22465–22471

    PubMed  Google Scholar 

  • Sugai M, Saito M, Sukegawa I, Katsushima Y, Kinouchi Y, Nakahata N, Shimosegawa T, Yanagisawa T, Sukegawa J (2003) PTH/PTH-related protein receptor interacts directly with Tctex-1 through its COOH terminus. Biochem Biophys Res Commun 311:24–31

    Article  PubMed  Google Scholar 

  • Tai AW, Chuang JZ, Bode C, Wolfrum U, Sung CH (1999) Rhodopsin’s carboxy-terminal cytoplasmic tail acts as a membrane receptor for cytoplasmic dynein by binding to the dynein light chain Tctex-1. Cell 97:877–887

    Article  PubMed  Google Scholar 

  • Takahashi H, Umeda N, Tsutsumi Y, Fukumura R, Ohkaze H, Sujino M, van der Horst G, Yasui A, Inouye ST, Fujimori A, Ohhata T, Araki R, Abe M (2003) Mouse dexamethasone-induced RAS protein 1 gene is expressed in a circadian rhythmic manner in the suprachiasmatic nucleus. Brain Res Mol Brain Res 110:1–6

    Article  PubMed  Google Scholar 

  • Takasaki J, Saito T, Taniguchi M, Kawasaki T, Moritani Y, Hayashi K, Kobori M (2004) A novel Galphaq/11-selective inhibitor. J Biol Chem 279:47438–47445

    Article  PubMed  Google Scholar 

  • Takesono A, Cismowski MJ, Ribas C, Bernard M, Chung P, Hazard S III, Duzic E, Lanier SM (1999) Receptor-independent activators of heterotrimeric G-protein signaling pathways. J Biol Chem 274:33202–33205

    Article  PubMed  Google Scholar 

  • Takesono A, Nowak MW, Cismowski M, Duzic E, Lanier SM (2002) Activator of G-protein signaling 1 blocks GIRK channel activation by a G-protein-coupled receptor: apparent disruption of receptor signaling complexes. J Biol Chem 277:13827–13830

    Article  PubMed  Google Scholar 

  • Tall GG, Krumins AM, Gilman AG (2003) Mammalian Ric-8A (synembryn) is a heterotrimeric Galpha protein guanine nucleotide exchange factor. J Biol Chem 278:8356–8362

    Article  PubMed  Google Scholar 

  • Tomita U, Takahashi K, Ikenaka K, Kondo T, Fujimoto I, Aimoto S, Mikoshiba K, Ui M, Katada T (1991) Direct activation of GTP-binding proteins by venom peptides that contain cationic clusters within their alpha-helical structures. Biochem Biophys Res Commun 178:400–406

    Article  PubMed  Google Scholar 

  • Toutant M, Aunis D, Bockaert J, Homburger V, Rouot B (1987) Presence of three pertussis toxin substrates and Go alpha immunoreactivity in both plasma and granule membranes of chromaffin cells. FEBS Lett 215:339–344

    Article  PubMed  Google Scholar 

  • Traver S, Splingard A, Gaudriault G, De Gunzburg J (2004) The RGS (regulator of G-protein signalling) and GoLoco domains of RGS14 co-operate to regulate Gi-mediated signalling. Biochem J 379:627–632

    Article  PubMed  Google Scholar 

  • Tu Y, Wu C (1999) Cloning, expression and characterization of a novel human Ras-related protein that is regulated by glucocorticoid hormone. Biochim Biophys Acta 1489:452–456

    PubMed  Google Scholar 

  • Vaidyanathan G, Cismowski MJ, Wang G, Vincent TS, Brown KD, Lanier SM (2004) The Ras-related protein AGS1/RASD1 suppresses cell growth. Oncogene 23:5858–5863

    Article  PubMed  Google Scholar 

  • Vargiu P, Morte B, Manzano J, Perez J, de Abajo R, Gregor Sutcliffe J, Bernal J (2001) Thyroid hormone regulation of rhes, a novel Ras homolog gene expressed in the striatum. Brain Res Mol Brain Res 94:1–8

    Article  PubMed  Google Scholar 

  • Vargiu P, De Abajo R, Garcia-Ranea JA, Valencia A, Santisteban P, Crespo P, Bernal J (2004) The small GTP-binding protein, Rhes, regulates signal transduction from G protein-coupled receptors. Oncogene 23:559–568

    Article  PubMed  Google Scholar 

  • Vos MD, Ellis CA, Bell A, Birrer MJ, Clark GJ (2000) Ras uses the novel tumor suppressor RASSF1 as an effector to mediate apoptosis. J Biol Chem 275:35669–35672

    Article  PubMed  Google Scholar 

  • Voss T, Wallner E, Czernilofsky AP, Freissmuth M (1993) Amphipathic alpha-helical structure does not predict the ability of receptor-derived synthetic peptides to interact with guanine nucleotide-binding regulatory proteins. J Biol Chem 268:4637–4642

    PubMed  Google Scholar 

  • Watts VJ (2002) Molecular mechanisms for heterologous sensitization of adenylate cyclase. J Pharmacol Exp Ther 302:1–7

    Article  PubMed  Google Scholar 

  • Webb CK, McCudden CR, Willard FS, Kimple RJ, Siderovski DP, Oxford GS (2005) D2 dopamine receptor activation of potassium channels is selectively decoupled by Galpha-specific GoLoco motif peptides. J Neurochem 92:1408–1418

    Article  PubMed  Google Scholar 

  • Weissman JT, Ma JN, Essex A, Gao Y, Burstein ES (2004) G-protein-coupled receptor-mediated activation of rap GTPases: characterization of a novel Galphai regulated pathway. Oncogene 23:241–249

    Article  PubMed  Google Scholar 

  • Willard FS, Kimple RJ, Siderovski DP (2004) Return of the GDI: the GoLoco motif in cell division. Annu Rev Biochem 73:925–951

    Article  PubMed  Google Scholar 

  • Winkler DG, Johnson JC, Cooper JA, Vojtek AB (1997) Identification and characterization of mutations in Ha-Ras that selectively decrease binding to cRaf-1. J Biol Chem 272:24402–24409

    Article  PubMed  Google Scholar 

  • Yamaguchi T, Nagahama M, Itoh H, Hatsuzawa K, Tani K, Tagaya M (2000) Regulation of the golgi structure by the alpha subunits of heterotrimeric G proteins. FEBS Lett 470:25–28

    Article  PubMed  Google Scholar 

  • Yamaguchi Y, Katoh H, Mori K, Negishi M (2002) Galpha(12) and Galpha(13) interact with Ser/Thr protein phosphatase type 5 and stimulate its phosphatase activity. Curr Biol 12:1353–1358

    Article  PubMed  Google Scholar 

  • Yao L, McFarland K, Fan P, Jiang Z, Inoue Y, Diamond I (2005) Activator of G protein signaling 3 regulates opiate activation of protein kinase A signaling and relapse of heroin-seeking behavior. Proc Natl Acad Sci U S A 102:8746–8751

    Article  PubMed  Google Scholar 

  • Yen KM (1998) Mammalian blood loss-induced gene, kd312. US Patent #6,462,177

  • Yu F, Morin X, Cai Y, Yang X, Chia W (2000) Analysis of partner of inscuteable, a novel player of Drosophila asymmetric divisions, reveals two distinct steps in inscuteable apical localization. Cell 100:399–409

    Article  PubMed  Google Scholar 

  • Zarling AL, Ficarro SB, White FM, Shabanowitz J, Hunt DF, Engelhard VH (2000) Phosphorylated peptides are naturally processed and presented by major histocompatibility complex class I molecules in vivo. J Exp Med 192:1755–1762

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by MH90531 (S.M.L.) and NS24821 (S.M.L.). S.M.L. is greatly appreciative for this support and that provided by the David R. Bethune/Lederle Laboratories Professorship in Pharmacology and the Research Scholar Award from Yamanouchi Pharmaceutical Company. The authors acknowledge the ongoing discussions with Dr. Emir Duzic (Cephalon) and the continuous input provided for this endeavor over the years by the many fellows and students who have spent time in the laboratory and the many colleagues with whom we have had the pleasure of working and publishing. We thank Yuri Peterson for allowing us to adapt Figs. 6 and 7 from his thesis. We also express our thanks to Dr. Offermans and the editorial board of the Reviews of Physiology, Biochemistry and Pharmacology for the opportunity to make this contribution to the journal.

Author information

Authors and Affiliations

  1. Department of Physiology and Pharmacology, Northeastern Ohio Universities College of Medicine, 4209 State Route 44, Rootstown, OH, USA

    M. J. Cismowski

  2. Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, 1901 Perdido Street, New Orleans, LA, USA

    S. M. Lanier

Authors
  1. M. J. Cismowski
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. M. Lanier
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S. M. Lanier.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cismowski, M.J., Lanier, S.M. Activation of heterotrimeric G-proteins independent of a G-protein coupled receptor and the implications for signal processing. Rev Physiol Biochem Pharmacol (2005). https://doi.org/10.1007/s10254-005-0042-z

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s10254-005-0042-z

Keywords

Search

Navigation