gtp binding protein beta subunits


Summary: Heterotrimeric GTP-binding protein subunits that tightly associate with GTP-BINDING PROTEIN GAMMA SUBUNITS. A dimer of beta and gamma subunits is formed when the GTP-BINDING PROTEIN ALPHA SUBUNIT dissociates from the GTP-binding protein heterotrimeric complex. The beta-gamma dimer can play an important role in signal transduction by interacting with a variety of second messengers.

Top Publications

  1. Witherow D, Slepak V. A novel kind of G protein heterodimer: the G beta5-RGS complex. Receptors Channels. 2003;9:205-12 pubmed
    ..This review summarizes the information about the assembly and function of G beta5-RGS dimers, as well as their posttranslational modifications and localization. ..
  2. Blackmer T, Larsen E, Bartleson C, Kowalchyk J, Yoon E, Preininger A, et al. G protein betagamma directly regulates SNARE protein fusion machinery for secretory granule exocytosis. Nat Neurosci. 2005;8:421-5 pubmed
    ..Here we show inhibitory coupling between GPCRs and vesicle exocytosis mediated directly by Gbetagamma interactions with the Ca(2+)-dependent fusion machinery. ..
  3. Krugmann S, Cooper M, Williams D, Hawkins P, Stephens L. Mechanism of the regulation of type IB phosphoinositide 3OH-kinase byG-protein betagamma subunits. Biochem J. 2002;362:725-31 pubmed
    ..We conclude that Gbetagammas activate type IB PI3K by a mechanism other than translocation to the plasma membrane. ..
  4. Taurin S, Hogarth K, Sandbo N, Yau D, Dulin N. Gbetagamma-mediated prostacyclin production and cAMP-dependent protein kinase activation by endothelin-1 promotes vascular smooth muscle cell hypertrophy through inhibition of glycogen synthase kinase-3. J Biol Chem. 2007;282:19518-25 pubmed
  5. Drenan R, Doupnik C, Jayaraman M, Buchwalter A, Kaltenbronn K, Huettner J, et al. R7BP augments the function of RGS7*Gbeta5 complexes by a plasma membrane-targeting mechanism. J Biol Chem. 2006;281:28222-31 pubmed
    ..Therefore, R7BP augments the function of the complex by a palmitoylation-regulated plasma membrane-targeting mechanism. ..
  6. Niu J, Profirovic J, Pan H, Vaiskunaite R, Voyno Yasenetskaya T. G Protein betagamma subunits stimulate p114RhoGEF, a guanine nucleotide exchange factor for RhoA and Rac1: regulation of cell shape and reactive oxygen species production. Circ Res. 2003;93:848-56 pubmed
    ..The findings help to explain the integrated effects of LPA and other G-protein receptor-coupled agonists on actin stress fiber formation, cell shape change, and ROS production. ..
  7. Ganem S, Lu S, Lee B, Chou D, Hadar R, Turgeon B, et al. G-protein beta subunit of Cochliobolus heterostrophus involved in virulence, asexual and sexual reproductive ability, and morphogenesis. Eukaryot Cell. 2004;3:1653-63 pubmed
    ..These data may be genetic evidence for a novel cell death-related function of the Gbeta subunit in filamentous fungi. ..
  8. Weitmann S, Schultz G, Kleuss C. Adenylyl cyclase type II domains involved in Gbetagamma stimulation. Biochemistry. 2001;40:10853-8 pubmed
  9. Chen S, Dell E, Lin F, Sai J, Hamm H. RACK1 regulates specific functions of Gbetagamma. J Biol Chem. 2004;279:17861-8 pubmed
    ..Similarly, RACK1 does not affect signal transduction through the Galpha subunits of G(i), G(s), or G(q). Collectively, these findings suggest a role of RACK1 in regulating specific functions of Gbetagamma. ..

More Information


  1. Cheever M, Snyder J, Gershburg S, Siderovski D, Harden T, Sondek J. Crystal structure of the multifunctional Gbeta5-RGS9 complex. Nat Struct Mol Biol. 2008;15:155-62 pubmed publisher
    ..This structure reveals a canonical RGS domain that is functionally integrated within a molecular complex that is poised for integration of multiple steps during G-protein activation and deactivation. ..
  2. Cabrera Vera T, Hernandez S, Earls L, Medkova M, Sundgren Andersson A, Surmeier D, et al. RGS9-2 modulates D2 dopamine receptor-mediated Ca2+ channel inhibition in rat striatal cholinergic interneurons. Proc Natl Acad Sci U S A. 2004;101:16339-44 pubmed
    ..These results implicate RGS9-2 as a specific regulator of dopamine receptor-mediated signaling in the striatum and identify a role for GAP activity modulation by the DEP-GGL domain. ..
  3. Blackmer T, Larsen E, Takahashi M, Martin T, Alford S, Hamm H. G protein betagamma subunit-mediated presynaptic inhibition: regulation of exocytotic fusion downstream of Ca2+ entry. Science. 2001;292:293-7 pubmed
    ..Thus, Gbetagamma blocked neurotransmitter release downstream of Ca2+ entry and may directly target the exocytotic fusion machinery at the presynaptic terminal. ..
  4. Menard R, Mattingly R. Gbetagamma subunits stimulate p21-activated kinase 1 (PAK1) through activation of PI3-kinase and Akt but act independently of Rac1/Cdc42. FEBS Lett. 2004;556:187-92 pubmed
    ..These results reveal that stimulation of PAK1 by Gbetagamma can occur via a PI3-kinase and Akt pathway that does not require Rac1 or Cdc42. ..
  5. Keresztes G, Martemyanov K, Krispel C, Mutai H, Yoo P, Maison S, et al. Absence of the RGS9.Gbeta5 GTPase-activating complex in photoreceptors of the R9AP knockout mouse. J Biol Chem. 2004;279:1581-4 pubmed
    ..Gbeta5 complex, and therefore all three proteins, RGS9, Gbeta5 , and R9AP, are obligate members of the regulatory complex that speeds the rate at which transducin hydrolyzes GTP. ..
  6. Jain S, Akiyama K, Kan T, Ohguchi T, Takata R. The G protein beta subunit FGB1 regulates development and pathogenicity in Fusarium oxysporum. Curr Genet. 2003;43:79-86 pubmed
    ..oxysporum. These results suggest that FGA1 and FGB1 have partially overlapping functions in the regulation of development and pathogenicity in F. oxysporum. ..
  7. Krispel C, Chen C, Simon M, Burns M. Prolonged photoresponses and defective adaptation in rods of Gbeta5-/- mice. J Neurosci. 2003;23:6965-71 pubmed
    ..In addition, our light adaptation studies support the notion than an additional weak GTPase-accelerating factor in rods is regulated by intracellular calcium and/or cGMP. ..
  8. Thornton C, Tang K, Phamluong K, Luong K, Vagts A, Nikanjam D, et al. Spatial and temporal regulation of RACK1 function and N-methyl-D-aspartate receptor activity through WD40 motif-mediated dimerization. J Biol Chem. 2004;279:31357-64 pubmed
    ..Based on these results, we propose that WD40-mediated homo- and heterodimerization of RACK1 mediate the formation of a transient signaling complex that includes the NMDAR, a G protein and Fyn. ..
  9. Mirshahi T, Mittal V, Zhang H, Linder M, Logothetis D. Distinct sites on G protein beta gamma subunits regulate different effector functions. J Biol Chem. 2002;277:36345-50 pubmed
    ..These data show that distinct domains within Gbetagamma subserve specific functional roles. ..
  10. Kawasaki L, Saviñón Tejeda A, Ongay Larios L, Ramirez J, Coria R. The Gbeta(KlSte4p) subunit of the heterotrimeric G protein has a positive and essential role in the induction of mating in the yeast Kluyveromyces lactis. Yeast. 2005;22:947-56 pubmed
    ..cerevisiae but fails to restore the mating deficiency of Scste4Delta mutant. The data presented indicate that the mating pathway of K. lactis is positively and cooperatively regulated by both the Galpha and the Gbeta subunits. ..
  11. Dignard D, Andre D, Whiteway M. Heterotrimeric G-protein subunit function in Candida albicans: both the alpha and beta subunits of the pheromone response G protein are required for mating. Eukaryot Cell. 2008;7:1591-9 pubmed publisher
  12. Bouhamdan M, Michelhaugh S, Calin Jageman I, Ahern Djamali S, Bannon M. Brain-specific RGS9-2 is localized to the nucleus via its unique proline-rich domain. Biochim Biophys Acta. 2004;1691:141-50 pubmed
    ..The nuclear localization of RGS9-2 suggests a heretofore-unanticipated role for this brain-specific protein in transducing signals to the nuclei of forebrain neurons. ..
  13. Delgado Jarana J, Martínez Rocha A, Roldán Rodríguez R, Roncero M, Di Pietro A. Fusarium oxysporum G-protein beta subunit Fgb1 regulates hyphal growth, development, and virulence through multiple signalling pathways. Fungal Genet Biol. 2005;42:61-72 pubmed
    ..Our results support a model in which Fgb1 controls hyphal growth, development and virulence in F. oxysporum both through cAMP-dependent and -independent pathways. ..
  14. Nishimura M, Park G, Xu J. The G-beta subunit MGB1 is involved in regulating multiple steps of infection-related morphogenesis in Magnaporthe grisea. Mol Microbiol. 2003;50:231-43 pubmed
    ..The Pmk1 pathway may be the downstream target of MGB1 for regulating penetration and infectious hyphae growth in M. grisea. ..
  15. Witherow D, Tovey S, Wang Q, Willars G, Slepak V. G beta 5.RGS7 inhibits G alpha q-mediated signaling via a direct protein-protein interaction. J Biol Chem. 2003;278:21307-13 pubmed
    ..Gbeta5 complex and cyan fluorescence protein-tagged Galphaq, indicating a direct interaction between these molecules. ..
  16. Chen S, Spiegelberg B, Lin F, Dell E, Hamm H. Interaction of Gbetagamma with RACK1 and other WD40 repeat proteins. J Mol Cell Cardiol. 2004;37:399-406 pubmed
    ..Here we will describe the molecular mechanism underlying this interaction and the implications of the interaction on the signal transduction of G-protein and RACK1. ..
  17. Robishaw J, Berlot C. Translating G protein subunit diversity into functional specificity. Curr Opin Cell Biol. 2004;16:206-9 pubmed
    ..Although much remains to be learned, the assembly of specific alphabetagamma subunit combinations seems to involve both structural and spatial factors. ..
  18. Goddard A, Ladds G, Forfar R, Davey J. Identification of Gnr1p, a negative regulator of G alpha signalling in Schizosaccharomyces pombe, and its complementation by human G beta subunits. Fungal Genet Biol. 2006;43:840-51 pubmed
    ..Human G beta subunits complement the loss of Gnr1p, functioning as negative regulators of G alpha signalling in fission yeast. ..
  19. Dohlman H, Thorner J. Regulation of G protein-initiated signal transduction in yeast: paradigms and principles. Annu Rev Biochem. 2001;70:703-54 pubmed
  20. Mirshahi T, Robillard L, Zhang H, Hebert T, Logothetis D. Gbeta residues that do not interact with Galpha underlie agonist-independent activity of K+ channels. J Biol Chem. 2002;277:7348-55 pubmed
    ..Our findings indicate that the presence of Gbeta residues that do not interact with Galpha are involved in Gbetagamma interactions in the absence of agonist stimulation. ..
  21. Murray D, McLaughlin S, Honig B. The role of electrostatic interactions in the regulation of the membrane association of G protein beta gamma heterodimers. J Biol Chem. 2001;276:45153-9 pubmed
    ..Sequence analysis and homology model building suggest that our conclusions may be generalized to other Gbetagamma and phosducin isoforms as well. ..
  22. Albsoul Younes A, Sternweis P, Zhao P, Nakata H, Nakajima S, Nakajima Y, et al. Interaction sites of the G protein beta subunit with brain G protein-coupled inward rectifier K+ channel. J Biol Chem. 2001;276:12712-7 pubmed
  23. Watson A, Katz A, Simon M. A fifth member of the mammalian G-protein beta-subunit family. Expression in brain and activation of the beta 2 isotype of phospholipase C. J Biol Chem. 1994;269:22150-6 pubmed
    ..The rather low level of identity between G beta 5 and the other mammalian G beta-subunits may shed light on structural/sequence elements necessary for G beta protein function. ..
  24. Song J, Hirschman J, Gunn K, Dohlman H. Regulation of membrane and subunit interactions by N-myristoylation of a G protein alpha subunit in yeast. J Biol Chem. 1996;271:20273-83 pubmed
    ..These data suggest that myristoylation is required for specific targeting of Gpa1p to the plasma membrane, where it is needed to interact with the receptor and to regulate the release of Gbetagamma. ..
  25. Hirschman J, De Zutter G, Simonds W, Jenness D. The G beta gamma complex of the yeast pheromone response pathway. Subcellular fractionation and protein-protein interactions. J Biol Chem. 1997;272:240-8 pubmed
    ..These results indicate that at least 40% of Ste4p and Ste18p are part of a G betagamma complex at the plasma membrane and that stable association of this complex with the plasma membrane requires the presence of G alpha. ..
  26. Inouye C, Dhillon N, Thorner J. Ste5 RING-H2 domain: role in Ste4-promoted oligomerization for yeast pheromone signaling. Science. 1997;278:103-6 pubmed
    ..Thus, the RING-H2 domain mediates Ste4-Ste5 interaction, which is a prerequisite for Ste5-Ste5 self-association and signaling. ..
  27. Leeuw T, Wu C, Schrag J, Whiteway M, Thomas D, Leberer E. Interaction of a G-protein beta-subunit with a conserved sequence in Ste20/PAK family protein kinases. Nature. 1998;391:191-5 pubmed
  28. Butty A, Pryciak P, Huang L, Herskowitz I, Peter M. The role of Far1p in linking the heterotrimeric G protein to polarity establishment proteins during yeast mating. Science. 1998;282:1511-6 pubmed
    ..Thus, Far1p functions as an adaptor that recruits polarity establishment proteins to the site of extracellular signaling marked by Gbetagamma to polarize assembly of the cytoskeleton in a morphogenetic gradient. ..
  29. Jamora C, Yamanouye N, van Lint J, Laudenslager J, Vandenheede J, Faulkner D, et al. Gbetagamma-mediated regulation of Golgi organization is through the direct activation of protein kinase D. Cell. 1999;98:59-68 pubmed
    ..Our findings suggest a possible mechanism by which the direct interaction of Gbetagamma with PKD regulates the dynamics of Golgi membranes and protein secretion. ..
  30. Hirschman J, Jenness D. Dual lipid modification of the yeast ggamma subunit Ste18p determines membrane localization of Gbetagamma. Mol Cell Biol. 1999;19:7705-11 pubmed
    ..We conclude that tight membrane attachment of the wild-type Gbetagamma depends on palmitoylation at Cys 106 and prenylation at Cys 107 of Ste18p. ..
  31. Dorer R, Pryciak P, Hartwell L. Saccharomyces cerevisiae cells execute a default pathway to select a mate in the absence of pheromone gradients. J Cell Biol. 1995;131:845-61 pubmed
    ..These observations reveal a molecular relationship between the mating and budding polarity pathways. ..
  32. Welton R, Hoffman C. Glucose monitoring in fission yeast via the Gpa2 galpha, the git5 Gbeta and the git3 putative glucose receptor. Genetics. 2000;156:513-21 pubmed
    ..Since the git3 deletion is fully suppressed by the gpa2(R176H) allele with respect to fbp1 transcription, git3 appears to encode a G protein-coupled glucose receptor responsible for adenylate cyclase activation in S. pombe. ..
  33. Rose J, Taylor J, Shi J, Cockett M, Jones P, Hepler J. RGS7 is palmitoylated and exists as biochemically distinct forms. J Neurochem. 2000;75:2103-12 pubmed
    ..These findings define previously unrecognized biochemical properties of RGS7, including the first demonstration that RGS7 is palmitoylated. ..
  34. Zhang J, Barr V, Mo Y, Rojkova A, Liu S, Simonds W. Nuclear localization of G protein beta 5 and regulator of G protein signaling 7 in neurons and brain. J Biol Chem. 2001;276:10284-9 pubmed
    ..RGS protein complexes suggests a potential role in neurons communicating between classical heterotrimeric G protein subunits and/or their effectors at the plasma membrane and the cell nucleus. ..
  35. Keren Raifman T, Bera A, Zveig D, Peleg S, Witherow D, Slepak V, et al. Expression levels of RGS7 and RGS4 proteins determine the mode of regulation of the G protein-activated K(+) channel and control regulation of RGS7 by G beta 5. FEBS Lett. 2001;492:20-8 pubmed
    ..These dual effects resolve previous controversies regarding RGS4 and RGS7 function and indicate that they modulate signaling by mechanisms supplementary to their GTPase-activating protein activity. ..
  36. Ongay Larios L, Saviñón Tejeda A, Williamson M, Durán Avelar M, Coria R. The Leu-132 of the Ste4(Gbeta) subunit is essential for proper coupling of the G protein with the Ste2 alpha factor receptor during the mating pheromone response in yeast. FEBS Lett. 2000;467:22-6 pubmed
  37. Landry S, Pettit M, Apolinario E, Hoffman C. The fission yeast git5 gene encodes a Gbeta subunit required for glucose-triggered adenylate cyclase activation. Genetics. 2000;154:1463-71 pubmed
  38. Xu B, Kurjan J. Evidence that mating by the Saccharomyces cerevisiae gpa1Val50 mutant occurs through the default mating pathway and a suggestion of a role for ubiquitin-mediated proteolysis. Mol Biol Cell. 1997;8:1649-64 pubmed
    ..On the basis of these results, we suggest that a positive component of the default mating pathway is subject to ubiquitin-mediated degradation. ..
  39. Gotta M, Ahringer J. Distinct roles for Galpha and Gbetagamma in regulating spindle position and orientation in Caenorhabditis elegans embryos. Nat Cell Biol. 2001;3:297-300 pubmed
    ..Gbetagamma is important in regulating migration of the centrosome around the nucleus and hence in orientating the mitotic spindle. Galpha is required for asymmetric spindle positioning in the one-celled embryo. ..
  40. Landry S, Hoffman C. The git5 Gbeta and git11 Ggamma form an atypical Gbetagamma dimer acting in the fission yeast glucose/cAMP pathway. Genetics. 2001;157:1159-68 pubmed
  41. Whiteway M, Clark K, Leberer E, Dignard D, Thomas D. Genetic identification of residues involved in association of alpha and beta G-protein subunits. Mol Cell Biol. 1994;14:3223-9 pubmed
    ..Because the ability of the modified G alpha subunit to suppress the Ste4 mutations is allele specific, it is likely that the residues defined by this analysis play a direct role in G-protein subunit association. ..
  42. Whiteway M, Wu C, Leeuw T, Clark K, Fourest Lieuvin A, Thomas D, et al. Association of the yeast pheromone response G protein beta gamma subunits with the MAP kinase scaffold Ste5p. Science. 1995;269:1572-5 pubmed
    ..Thus, association of the G protein and the MAP kinase cassette via the scaffolding protein Ste5p may transmit the G protein signal. ..
  43. Zhao Z, Leung T, Manser E, Lim L. Pheromone signalling in Saccharomyces cerevisiae requires the small GTP-binding protein Cdc42p and its activator CDC24. Mol Cell Biol. 1995;15:5246-57 pubmed
    ..The two-hybrid system revealed that Ste4p interacts with Cdc24p. We propose that Cdc42p plays a pivotal role both in polarization of the cytoskeleton and in pheromone signalling. ..
  44. Evanko D, Thiyagarajan M, Siderovski D, Wedegaertner P. Gbeta gamma isoforms selectively rescue plasma membrane localization and palmitoylation of mutant Galphas and Galphaq. J Biol Chem. 2001;276:23945-53 pubmed
  45. Reusch H, Schaefer M, Plum C, Schultz G, Paul M. Gbeta gamma mediate differentiation of vascular smooth muscle cells. J Biol Chem. 2001;276:19540-7 pubmed
    ..We conclude that receptor-mediated differentiation of VSM cells requires Gbetagamma and an intact Ras/Raf/MEK/ERK signaling. ..
  46. Krugmann S, Hawkins P, Pryer N, Braselmann S. Characterizing the interactions between the two subunits of the p101/p110gamma phosphoinositide 3-kinase and their role in the activation of this enzyme by G beta gamma subunits. J Biol Chem. 1999;274:17152-8 pubmed
    ..While modifications of the N terminus of p110gamma could modulate its intrinsic catalytic activity, binding to the N-terminal region of p101 was found to be indispensable for activation of heterodimers with Gbetagamma. ..
  47. Casarosa P, Gruijthuijsen Y, Michel D, Beisser P, Holl J, Fitzsimons C, et al. Constitutive signaling of the human cytomegalovirus-encoded receptor UL33 differs from that of its rat cytomegalovirus homolog R33 by promiscuous activation of G proteins of the Gq, Gi, and Gs classes. J Biol Chem. 2003;278:50010-23 pubmed
    ..Thus, HCMV may effectively use UL33 to orchestrate multiple signaling networks within infected cells. ..
  48. Shi C, Szczesniak A, Mao L, Jollimore C, Coca Prados M, Hung O, et al. A3 adenosine and CB1 receptors activate a PKC-sensitive Cl- current in human nonpigmented ciliary epithelial cells via a G beta gamma-coupled MAPK signaling pathway. Br J Pharmacol. 2003;139:475-86 pubmed
    ..8) We conclude that both A3 and CB1 receptors activate a PKC-sensitive Cl(-) current in human NPCE cells via a G(i/o)/Gbetagamma signaling pathway, in a manner independent of PI3K but involving MAPK. ..
  49. Romo X, Hinrichs M, Guzman L, Olate J. G(alpha)s levels regulate Xenopus laevis oocyte maturation. Mol Reprod Dev. 2002;63:104-9 pubmed
  50. Molina Muñoz T, Romero Ávila M, García Sáinz J. Insulin-like growth factor-I induces alpha(1B)-adrenergic receptor phosphorylation through G beta gamma and epidermal growth factor receptor transactivation. Mol Endocrinol. 2006;20:2773-83 pubmed
  51. Kumar P, Wu Q, Chambliss K, Yuhanna I, Mumby S, Mineo C, et al. Direct interactions with G ? i and G ?? mediate nongenomic signaling by estrogen receptor ? . Mol Endocrinol. 2007;21:1370-80 pubmed
    ..Thus, through direct interactions, ER alpha mediates a novel mechanism of G protein activation that provides greater diversity of function of both the steroid hormone receptor and G proteins. ..
  52. Kopf D, Cheng L, Blandau P, Hsueh W, Raffel L, Buchanan T, et al. Association of insulin sensitivity and glucose tolerance with the c.825C>T variant of the G protein beta-3 subunit gene. J Diabetes Complications. 2008;22:205-9 pubmed publisher
    ..Blood pressure did not differ significantly between the phenotypes. In a Mexican-American hypertensive population, we found evidence for higher insulin sensitivity in carriers of the T allele of the c.825C>T variant of GNB3. ..
  53. Guzman L, Moraga Cid G, Avila A, Figueroa M, Yevenes G, Fuentealba J, et al. Blockade of ethanol-induced potentiation of glycine receptors by a peptide that interferes with Gbetagamma binding. J Pharmacol Exp Ther. 2009;331:933-9 pubmed publisher