G2Cdb::Gene report

Gene id
G00001484
Gene symbol
GNB4 (HGNC)
Species
Homo sapiens
Description
guanine nucleotide binding protein (G protein), beta polypeptide 4
Orthologue
G00000235 (Mus musculus)

Databases (7)

Gene
ENSG00000114450 (Ensembl human gene)
59345 (Entrez Gene)
27 (G2Cdb plasticity & disease)
GNB4 (GeneCards)
Literature
610863 (OMIM)
Marker Symbol
HGNC:20731 (HGNC)
Protein Sequence
Q9HAV0 (UniProt)

Literature (19)

Pubmed - other

  • Association of GNB4 intron-1 haplotypes with survival in patients with UICC stage III and IV colorectal carcinoma.

    Riemann K, Struwe H, Alakus H, Obermaier B, Schmitz KJ, Schmid KW and Siffert W

    University Hospital Essen, Hufelandstr. 55, 45147 Essen, Germany. kathrin.riemann@uk-essen.de

    Background: Polymorphisms in genes encoding subunits of heterotrimeric G proteins have been repeatedly associated with the course of cancer. As previously shown, intron 1 of GNB4 harbours distinct haplotype blocks and block 1 is associated with survival and disease progression in urothelial bladder cancer. This study investigated whether haplotype block 2 is associated with survival in colorectal cancer patients.

    The haplotype tagging polymorphism of GNB4 haplotype block 2 was genotyped in 136 colorectal cancer patients and associated with demographic and clinical data and survival.

    Results: Haplotype block 2 is associated with survival in colorectal cancer patients. Patients with advanced tumour stages carrying the 2*1 haplotype revealed decreased survival (HR 2.04, 95% CI 0.91-3.69). In multivariate analysis, the diplotypes were independent prognostic factors.

    Conclusion: Intron-1 haplotypes of GNB4 might be predictive markers for survival of patients with advanced colorectal cancer, thus influencing the clinical management of these patients.

    Anticancer research 2009;29;4;1271-4

  • Characterization of intron-1 haplotypes of the G protein beta 4 subunit gene--association with survival and progression in patients with urothelial bladder carcinoma.

    Riemann K, Struwe H, Eisenhardt A, Obermaier B, Schmid KW and Siffert W

    Institute of Pharmacogenetics, University Hospital, University of Duisburg-Essen, Essen, Germany. kathrin.riemann@uk-essen.de

    Purpose: Polymorphisms in genes encoding subunits of heterotrimeric G proteins have been repeatedly associated with various cancers. As G beta gamma signaling is presumed to be involved in proliferation and invasion processes, we analyzed genetic variations in regulatory regions of GNB4, which encodes the G beta 4 subunit, for their potential influence on cancer progression.

    We characterized the promoter of GNB4 and screened the promoter as well as exon 1 and intron 1 for single nucleotide polymorphisms by sequencing 100 healthy controls. Following a haplotype analysis, we determined the functional impact upon gene expression of the defined haplotypes by reporter assays, electrophoretic mobility shift assay and western blot. In addition, these haplotypes were tested for their relation to the disease course of urothelial bladder cancer.

    Results: Whereas the promoter of GNB4 revealed no polymorphisms, 33 single nucleotide polymorphisms located in exon 1 and intron 1 were identified and together with a common exon-4 polymorphism implemented in haplotype analysis, which resulted in the determination of distinct haplotype blocks. Reporter activity was haplotype-dependently different (P=0.001). 1*1/1*1 showed increased G beta 4 protein (P=0.003), and bladder cancer patients carrying this diplotype displayed more progressive disease (P=0.046) and a significantly increased mortality (P=0.046). In multivariate analysis,the diplotypes were independent prognostic factors for survival and progression.

    Conclusion: Intron-1 haplotypes of GNB4 may, thus, serve as predictive markers for progression and survival of patients suffering from bladder cancer.

    Pharmacogenetics and genomics 2008;18;11;999-1008

  • Purification and identification of G protein-coupled receptor protein complexes under native conditions.

    Daulat AM, Maurice P, Froment C, Guillaume JL, Broussard C, Monsarrat B, Delagrange P and Jockers R

    Department of Cell Biology, Institut Cochin, INSERM U567, CNRS UMR 8104, Université Paris Descartes, France.

    G protein-coupled receptors (GPCRs) constitute the largest family of membrane receptors and are of major therapeutic importance. The identification of GPCR-associated proteins is an important step toward a better understanding of these receptors. However, current methods are not satisfying as only isolated receptor domains (intracellular loops or carboxyl-terminal tails) can be used as "bait." We report here a method based on tandem affinity purification coupled to mass spectrometry that overcomes these limitations as the entire receptor is used to identify protein complexes formed in living mammalian cells. The human MT(1) and MT(2) melatonin receptors were chosen as model GPCRs. Both receptors were tagged with the tandem affinity purification tag at their carboxyl-terminal tails and expressed in human embryonic kidney 293 cells. Receptor solubilization and purification conditions were optimized. The method was validated by the co-purification of G(i) proteins, which are well known GPCR interaction partners but which are difficult to identify with current protein-protein interaction assays. Several new and functionally relevant MT(1)- and MT(2)-associated proteins were identified; some of them were common to both receptors, and others were specific for each subtype. Taken together, our protocol allowed for the first time the purification of GPCR-associated proteins under native conditions in quantities suitable for mass spectrometry analysis.

    Molecular & cellular proteomics : MCP 2007;6;5;835-44

  • Identification of Gnr1p, a negative regulator of G alpha signalling in Schizosaccharomyces pombe, and its complementation by human G beta subunits.

    Goddard A, Ladds G, Forfar R and Davey J

    Department of Biological Sciences, University of Warwick, Coventry, UK. A.D.Goddard@warwick.ac.uk

    G protein-coupled receptors (GPCRs) are involved in the response of eukaryotic cells to a wide variety of stimuli, traditionally mediating their effects through heterotrimeric G proteins comprised of G alpha, G beta and G gamma subunits. The fission yeast Schizosaccharomyces pombe is an established tool for GPCR research, possessing two G alpha-dependent signalling cascades. A complete G alpha beta gamma complex has been characterised for the glucose-sensing pathway, but only the G alpha subunit, Gpa1p, has been identified in the pheromone-response pathway. Here, we report the use of the yeast two-hybrid system to identify a novel protein, Gnr1p, which interacts with Gpa1p. Gnr1p is predicted to contain seven WD repeats and to adopt a structure similar to typical G beta subunits. Disruption and overexpression studies reveal that Gnr1p negatively regulates the pheromone-response pathway but is not required for signalling. Human G beta subunits complement the loss of Gnr1p, functioning as negative regulators of G alpha signalling in fission yeast.

    Fungal genetics and biology : FG & B 2006;43;12;840-51

  • The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

    Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Morrin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J and MGC Project Team

    The National Institutes of Health's Mammalian Gene Collection (MGC) project was designed to generate and sequence a publicly accessible cDNA resource containing a complete open reading frame (ORF) for every human and mouse gene. The project initially used a random strategy to select clones from a large number of cDNA libraries from diverse tissues. Candidate clones were chosen based on 5'-EST sequences, and then fully sequenced to high accuracy and analyzed by algorithms developed for this project. Currently, more than 11,000 human and 10,000 mouse genes are represented in MGC by at least one clone with a full ORF. The random selection approach is now reaching a saturation point, and a transition to protocols targeted at the missing transcripts is now required to complete the mouse and human collections. Comparison of the sequence of the MGC clones to reference genome sequences reveals that most cDNA clones are of very high sequence quality, although it is likely that some cDNAs may carry missense variants as a consequence of experimental artifact, such as PCR, cloning, or reverse transcriptase errors. Recently, a rat cDNA component was added to the project, and ongoing frog (Xenopus) and zebrafish (Danio) cDNA projects were expanded to take advantage of the high-throughput MGC pipeline.

    Funded by: PHS HHS: N01-C0-12400

    Genome research 2004;14;10B;2121-7

  • Complete sequencing and characterization of 21,243 full-length human cDNAs.

    Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T and Sugano S

    Helix Research Institute, 1532-3 Yana, Kisarazu, Chiba 292-0812, Japan.

    As a base for human transcriptome and functional genomics, we created the "full-length long Japan" (FLJ) collection of sequenced human cDNAs. We determined the entire sequence of 21,243 selected clones and found that 14,490 cDNAs (10,897 clusters) were unique to the FLJ collection. About half of them (5,416) seemed to be protein-coding. Of those, 1,999 clusters had not been predicted by computational methods. The distribution of GC content of nonpredicted cDNAs had a peak at approximately 58% compared with a peak at approximately 42%for predicted cDNAs. Thus, there seems to be a slight bias against GC-rich transcripts in current gene prediction procedures. The rest of the cDNAs unique to the FLJ collection (5,481) contained no obvious open reading frames (ORFs) and thus are candidate noncoding RNAs. About one-fourth of them (1,378) showed a clear pattern of splicing. The distribution of GC content of noncoding cDNAs was narrow and had a peak at approximately 42%, relatively low compared with that of protein-coding cDNAs.

    Nature genetics 2004;36;1;40-5

  • The human G protein beta4 subunit: gene structure, expression, Ggamma and effector interaction.

    Rosskopf D, Nikula C, Manthey I, Joisten M, Frey U, Kohnen S and Siffert W

    Institut für Pharmakologie, Universitätsklinikum Essen, Hufelandstr. 55, Germany. dieter.rosskopf@uni-essen.de

    The aim of this study was the characterization of the human Gbeta4 subunit of heterotrimeric G proteins. Human Gbeta4 is widely expressed. Its gene is located on chromosome 3 with a genomic structure indistinguishable from that of the genes of Gbeta1 to Gbeta3, but entirely different from Gbeta5. In vitro translation co-precipitation analyses revealed that Gbeta4 can form stable dimers with Ggamma1, Ggamma2, Ggamma3, Ggamma4, Ggamma5, Ggamma7, Ggamma10, Ggamma11, Ggamma12, and Ggamma13, dimers which were also able to stimulate phospholipase beta2.

    FEBS letters 2003;544;1-3;27-32

  • Glucagon and regulation of glucose metabolism.

    Jiang G and Zhang BB

    Department of Metabolic Disorders and Molecular Endocrinology, Merck Research Laboratory, Rahway, New Jersey 07065, USA.

    As a counterregulatory hormone for insulin, glucagon plays a critical role in maintaining glucose homeostasis in vivo in both animals and humans. To increase blood glucose, glucagon promotes hepatic glucose output by increasing glycogenolysis and gluconeogenesis and by decreasing glycogenesis and glycolysis in a concerted fashion via multiple mechanisms. Compared with healthy subjects, diabetic patients and animals have abnormal secretion of not only insulin but also glucagon. Hyperglucagonemia and altered insulin-to-glucagon ratios play important roles in initiating and maintaining pathological hyperglycemic states. Not surprisingly, glucagon and glucagon receptor have been pursued extensively in recent years as potential targets for the therapeutic treatment of diabetes.

    American journal of physiology. Endocrinology and metabolism 2003;284;4;E671-8

  • Activation of heterotrimeric G proteins by a high energy phosphate transfer via nucleoside diphosphate kinase (NDPK) B and Gbeta subunits. Complex formation of NDPK B with Gbeta gamma dimers and phosphorylation of His-266 IN Gbeta.

    Cuello F, Schulze RA, Heemeyer F, Meyer HE, Lutz S, Jakobs KH, Niroomand F and Wieland T

    Institut für Pharmakologie und Toxikologie, Fakultät für Klinische Medizin Mannheim, Universität Heidelberg, Maybachstrasse 14-16, D-68169 Mannheim, Germany.

    G protein betagamma dimers can be phosphorylated in membranes from various tissues by GTP at a histidine residue in the beta subunit. The phosphate is high energetic and can be transferred onto GDP leading to formation of GTP. Purified Gbetagamma dimers do not display autophosphorylation, indicating the involvement of a separate protein kinase. We therefore enriched the Gbeta-phosphorylating activity present in preparations of the retinal G protein transducin and in partially purified G(i/o) proteins from bovine brain. Immunoblots, autophosphorylation, and enzymatic activity measurements demonstrated enriched nucleoside diphosphate kinase (NDPK) B in both preparations, together with residual Gbetagamma dimers. In the retinal NDPK B-enriched fractions, a Gbeta-specific antiserum co-precipitated phosphorylated NDPK B, and an antiserum against the human NDPK co-precipitated phosphorylated Gbetagamma. In addition, the NDPK-containing fractions from bovine brain reconstituted the phosphorylation of purified Gbetagamma. For identification of the phosphorylated histidine residue, bovine brain Gbetagamma and G(t)betagamma were thiophosphorylated with guanosine 5'-O-(3-[(35)S]thio)triphosphate, followed by digestion with endoproteinase Glu-C and trypsin, separation of the resulting peptides by gel electrophoresis and high pressure liquid chromatography, respectively, and sequencing of the radioactive peptides. The sequence information produced by both methods identified specific labeled fragments of bovine Gbeta(1) that overlapped in the heptapeptide, Leu-Met-Thr-Tyr-Ser-His-Asp (amino acids 261-267). We conclude that NDPK B forms complexes with Gbetagamma dimers and contributes to G protein activation by increasing the high energetic phosphate transfer onto GDP via intermediately phosphorylated His-266 in Gbeta(1) subunits.

    The Journal of biological chemistry 2003;278;9;7220-6

  • G protein subunit G gamma 13 is coexpressed with G alpha o, G beta 3, and G beta 4 in retinal ON bipolar cells.

    Huang L, Max M, Margolskee RF, Su H, Masland RH and Euler T

    Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York, New York 10029, USA.

    We investigated the expression of Ggamma13, a recently discovered G protein subunit, and a selection of Gbeta subunits in retinal bipolar cells, by using a transgenic mouse strain in which green fluorescent protein is strongly expressed in a single type of cone bipolar cell. The cells have ON morphology, and patch-clamp recordings in slices confirmed that they are of the physiological ON type. Immunohistochemistry showed that Ggamma13 is expressed in rod bipolar cells and ON cone bipolar cells, where it is colocalized in the dendrites with Galphaomicron. ON and OFF cone bipolar cells and rod bipolar cells were identified among dissociated cells by their green fluorescence and/or distinct morphology. Hybridization of single-cell polymerase chain reaction products with cDNA probes for G protein subunits Gbeta1 to 5 showed that Gbeta3, Gbeta4, and Ggamma13 are coexpressed in ON bipolar cells but not present in OFF bipolar cells. Gbeta1, 2, and 5 are expressed in partially overlapping subpopulations of cone bipolar cells. Ggamma13 and Gbeta3 and/or Gbeta4, thus, seem selectively to participate in signal transduction by ON bipolar cells.

    Funded by: NIDCD NIH HHS: DC00310, DC03155; NIMH NIH HHS: MHS7241

    The Journal of comparative neurology 2003;455;1;1-10

  • The role of G protein beta subunits in the release of ATP from human erythrocytes.

    Sprague RS, Bowles EA, Olearczyk JJ, Stephenson AH and Lonigro AJ

    Saint Louis University School of Medicine, MO 63104, USA. spraguer@slu.edu

    Previously, we demonstrated that adenosine triphosphate (ATP) is released from human erythrocytes in response to mechanical deformation and that this release requires activation of a signal-transduction pathway involving adenylyl cyclase and the heterotrimeric G protein, Gs. Here we investigate the role of heterotrimeric G proteins of the Gi subtype in the release of ATP from human erythrocytes. In addition, we determined the profile of heterotrimeric G protein beta subunits present in these erythrocyte membranes. The activity of Gi was stimulated by incubation of erythrocytes (20% hematocrit) with mastoparin (10 microM). ATP release was measured using the luciferin/luciferase assay. Heterotrimeric G protein beta subunits present in erythrocyte membranes were resolved using gel electrophoresis and subunit specific antibodies. Incubation of human erythrocytes with mastoparan (an activator of Gi/o) resulted in a 4.1 +/- 0.6-fold increase in ATP present in the medium (P<0.01). Human erythrocyte membranes stain positively for beta subunit types 1, 2, 3 and 4, all of which been reported to activate of some isoforms of adenylyl cyclase. Activation of the heterotrimeric G protein, Gi, results in ATP release from erythrocytes. This effect is may be related to the activity of beta subunits associated with this G protein in the human erythrocyte.

    Funded by: NHLBI NIH HHS: HL-39226, HL-51298, HL-52675

    Journal of physiology and pharmacology : an official journal of the Polish Physiological Society 2002;53;4 Pt 1;667-74

  • Cloning, tissue distribution, and functional expression of the human G protein beta 4-subunit.

    Ruiz-Velasco V, Ikeda SR and Puhl HL

    Laboratory of Molecular Physiology, cDNA Resource Center, Guthrie Research Institute, Sayre, Pennsylvania 18840, USA.

    Heterotrimeric G proteins (Galphabetagamma) play an essential role in coupling membrane receptors to effector proteins such as ion channels and enzymes. Among the five mammalian Gbeta-subunits cloned, the human G protein beta4 has not been described. The purpose of the present study was to functionally characterize the newly identified human Gbeta4 subunit. The Gbeta4 open reading frame (ORF) was amplified utilizing PCR from brain cDNA. Amplification primers were generated following 5' rapid amplification of cDNA ends (5'-RACE) from an expressed sequence tag (EST) containing the predicted 3' end of the protein. Multiple tissue cDNA panel analysis showed that Gbeta4 mRNA was strongly expressed in lung and placenta, whereas it is weakly expressed in brain and heart. Heterologous overexpression of Gbeta4gamma2 or Gbeta4gamma4 in rat sympathetic neurons resulted in tonic modulation of N-type voltage-gated Ca(2+) and G protein-gated inwardly rectifying K(+) currents. Furthermore, coexpression of Gbeta4gamma2 and Galpha(oA) resulted in heterotrimer formation. These results show that the newly cloned Gbeta subunit shares several properties with other human Gbeta family members.

    Funded by: NIGMS NIH HHS: GM-56180; NIMH NIH HHS: MH-12288

    Physiological genomics 2002;8;1;41-50

  • Gbeta gamma isoforms selectively rescue plasma membrane localization and palmitoylation of mutant Galphas and Galphaq.

    Evanko DS, Thiyagarajan MM, Siderovski DP and Wedegaertner PB

    Department of Microbiology and Immunology and Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.

    Mutation of Galpha(q) or Galpha(s) N-terminal contact sites for Gbetagamma resulted in alpha subunits that failed to localize at the plasma membrane or undergo palmitoylation when expressed in HEK293 cells. We now show that overexpression of specific betagamma subunits can recover plasma membrane localization and palmitoylation of the betagamma-binding-deficient mutants of alpha(s) or alpha(q). Thus, the betagamma-binding-defective alpha is completely dependent on co-expression of exogenous betagamma for proper membrane localization. In this report, we examined the ability of beta(1-5) in combination with gamma(2) or gamma(3) to promote proper localization and palmitoylation of mutant alpha(s) or alpha(q). Immunofluorescence localization, cellular fractionation, and palmitate labeling revealed distinct subtype-specific differences in betagamma interactions with alpha subunits. These studies demonstrate that 1) alpha and betagamma reciprocally promote the plasma membrane targeting of the other subunit; 2) beta(5), when co-expressed with gamma(2) or gamma(3), fails to localize to the plasma membrane or promote plasma membrane localization of mutant alpha(s) or alpha(q); 3) beta(3) is deficient in promoting plasma membrane localization of mutant alpha(s) and alpha(q), whereas beta(4) is deficient in promoting plasma membrane localization of mutant alpha(q); 4) both palmitoylation and interactions with betagamma are required for plasma membrane localization of alpha.

    Funded by: NIGMS NIH HHS: GM56444

    The Journal of biological chemistry 2001;276;26;23945-53

  • The G protein subunit gene families.

    Downes GB and Gautam N

    Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

    Genomics 1999;62;3;544-52

  • Ggamma13 colocalizes with gustducin in taste receptor cells and mediates IP3 responses to bitter denatonium.

    Huang L, Shanker YG, Dubauskaite J, Zheng JZ, Yan W, Rosenzweig S, Spielman AI, Max M and Margolskee RF

    Howard Hughes Medical Institute, Mount Sinai School of Medicine of New York University, Box 1677, One Gustave L. Levy Place, New York, New York 10029, USA.

    Gustducin is a transducin-like G protein selectively expressed in taste receptor cells. The alpha subunit of gustducin (alpha-gustducin) is critical for transduction of responses to bitter or sweet compounds. We identified a G-protein gamma subunit (Ggamma13) that colocalized with alpha-gustducin in taste receptor cells. Of 19 alpha-gustducin/Ggamma13-positive taste receptor cells profiled, all expressed the G protein beta3 subunit (Gbeta3); approximately 80% also expressed Gbeta1. Gustducin heterotrimers (alpha-gustducin/Gbeta1/Ggamma13) were activated by taste cell membranes plus bitter denatonium. Antibodies against Ggamma13 blocked the denatonium-induced increase of inositol trisphosphate (IP3) in taste tissue. We conclude that gustducin heterotrimers transduce responses to bitter and sweet compounds via alpha-gustducin's regulation of phosphodiesterase (PDE) and Gbetagamma's activation of phospholipase C (PLC).

    Funded by: NIDCD NIH HHS: DC03155; NIDCR NIH HHS: DE10754; NIMH NIH HHS: MH57241; ...

    Nature neuroscience 1999;2;12;1055-62

  • Selective association of G protein beta(4) with gamma(5) and gamma(12) subunits in bovine tissues.

    Asano T, Morishita R, Ueda H and Kato K

    Department of Biochemistry, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi 480-0392, Japan. toasano@inst-hsc.pref.aichi.jp

    The beta and gamma subunits of G proteins are tightly bound under physiological conditions, and so far, seven beta and 11 gamma subunit isoforms have been found. The relative abilities of the beta and gamma subunits to associate with each other have been studied using transfected cell assays, in vitro translation and the yeast two-hybrid system, but have not been fully characterized in various tissues. In the present study, we demonstrated the selectivity of association of the beta with gamma isoforms in bovine tissues. Immunoprecipitation of betagamma complexes from tissue extracts with antibodies against various gamma subunits and subsequent analyses revealed that beta(4) associated with the gamma subunits with the following rank order of selectivity: gamma(5) > gamma(12) > gamma(2) > gamma(3), while beta(2) bound to gamma(2), gamma(3), and gamma(12) more selectively than to gamma(5). By contrast, beta(1) associated with all gamma subunits without significant selectivity. Analyses of purified betagamma complexes containing various gamma isoforms revealed beta subunit compositions similar to those found in the immunoprecipitates. Particular combinations of beta and gamma subunit isoforms may contribute to maintaining efficient and specific signal transduction mediated by G proteins.

    The Journal of biological chemistry 1999;274;30;21425-9

  • Selectively enhanced cellular signaling by Gi proteins in essential hypertension. G alpha i2, G alpha i3, G beta 1, and G beta 2 are not mutated.

    Pietruck F, Moritz A, Montemurro M, Sell A, Busch S, Rosskopf D, Virchow S, Esche H, Brockmeyer N, Jakobs KH and Siffert W

    Institut für Pharmakologie, Universitätsklinikum Essen (Germany).

    Recent studies have shown an enhanced signaling capacity of receptors coupled to pertussis toxin (PTX)-sensitive guanine nucleotide-binding proteins (G proteins) in immortalized B lymphoblasts from patients with essential hypertension. In the present study, we analyzed (1) whether such alterations would also be expressed in nontransformed cells of these individuals and (2) whether other G protein-mediated signaling pathways were also altered. Therefore, we established primary cultures of skin fibroblasts from previously characterized normotensive and hypertensive individuals (NT and HT cells, respectively). [Ca2+]i rises induced by lyso-phosphatidic acid (LPA), thrombin, and sphingosine-1-phosphate as well as the formation of inositol 1,4,5-trisphosphate and [3H]thymidine incorporation evoked by LPA were PTX sensitive and enhanced twofold in HT fibroblasts. In contrast, cellular responses induced by bradykinin, endothelin-1, and angiotensin II (all PTX insensitive) were similar in NT and HT cells. Formation of cAMP induced by stimulation of Gs with isoproterenol was identical in NT and HT cells. Western blot analysis yielded no evidence for an overexpression of G alpha i2, G alpha i3, G beta 2, and G beta 4. Furthermore, sequencing of cDNAs encoding for the ubiquitously expressed PTX-sensitive G protein subunits G alpha i2, G alpha i3, G beta 1, and G beta 2 from NT and HT cell lines yielded no evidence for mutations in these genes. Although the molecular mechanisms remain to be defined, these data support the concept of a selective enhancement of signal transduction via PTX-sensitive G proteins in essential hypertension.

    Circulation research 1996;79;5;974-83

  • Differential ability to form the G protein betagamma complex among members of the beta and gamma subunit families.

    Yan K, Kalyanaraman V and Gautam N

    Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

    We have determined the relative abilities of several members of the G protein beta and gamma subunit families to associate with each other using the yeast two-hybrid system. We show first that the mammalian beta1 and gamma3 fusion proteins form a complex in yeast and that formation of the complex activates the reporter gene for beta-galactosidase. Second, the magnitude of reporter activity stimulated by various combinations of beta and gamma subunit types varies widely. Third, the reporter activity evoked by a particular combination of beta and gamma subunit types is not correlated with the expression levels of these subunit types in the yeast cells. Finally, the reporter activity shows a direct relationship with the amount of hybrid betagamma complex formed in the cell as determined by immunoprecipitation. These results suggest that different beta and gamma subunit types interact with each other with widely varying abilities, and this in combination with the level of expression of a subunit type in a mammalian cell determines which G protein will be active in that cell. The strong preference of all gamma subunit types for the beta1 subunit type explains the preponderence of this subunit type in most G proteins.

    The Journal of biological chemistry 1996;271;12;7141-6

Gene lists (7)

Gene List Source Species Name Description Gene count
L00000015 G2C Homo sapiens Human NRC Human orthologues of mouse NRC adapted from Collins et al (2006) 186
L00000016 G2C Homo sapiens Human PSP Human orthologues of mouse PSP adapted from Collins et al (2006) 1121
L00000033 G2C Homo sapiens Pocklington H2 Human orthologues of cluster 2 (mouse) from Pocklington et al (2006) 13
L00000059 G2C Homo sapiens BAYES-COLLINS-HUMAN-PSD-CONSENSUS Human cortex PSD consensus 748
L00000061 G2C Homo sapiens BAYES-COLLINS-MOUSE-PSD-CONSENSUS Mouse cortex PSD consensus (ortho) 984
L00000069 G2C Homo sapiens BAYES-COLLINS-HUMAN-PSD-FULL Human cortex biopsy PSD full list 1461
L00000071 G2C Homo sapiens BAYES-COLLINS-MOUSE-PSD-FULL Mouse cortex PSD full list (ortho) 1556
© G2C 2014. The Genes to Cognition Programme received funding from The Wellcome Trust and the EU FP7 Framework Programmes:
EUROSPIN (FP7-HEALTH-241498), SynSys (FP7-HEALTH-242167) and GENCODYS (FP7-HEALTH-241995).

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