gtp binding protein regulators


Summary: Proteins that regulate the signaling activity of GTP-BINDING PROTEINS. They are divided into three categories depending upon whether they stimulate GTPase activity (GTPASE-ACTIVATING PROTEINS), inhibit release of GDP; (GUANINE NUCLEOTIDE DISSOCIATION INHIBITORS); or exchange GTP for GDP; (GUANINE NUCLEOTIDE EXCHANGE FACTORS).

Top Publications

  1. Beetz N, Harrison M, Brede M, Zong X, Urbanski M, Sietmann A, et al. Phosducin influences sympathetic activity and prevents stress-induced hypertension in humans and mice. J Clin Invest. 2009;119:3597-3612 pubmed publisher
    ..These findings demonstrate that PDC is an important modulator of sympathetic activity and blood pressure and may thus represent a promising target for treatment of stress-dependent hypertension. ..
  2. Klenk C, Humrich J, Quitterer U, Lohse M. SUMO-1 controls the protein stability and the biological function of phosducin. J Biol Chem. 2006;281:8357-64 pubmed
    ..Together, these findings show that phosducin is a previously unrecognized target of SUMO modification and that SUMOylation controls phosducin stability in cells as well as its functional properties. ..
  3. Sokolov M, Strissel K, Leskov I, Michaud N, Govardovskii V, Arshavsky V. Phosducin facilitates light-driven transducin translocation in rod photoreceptors. Evidence from the phosducin knockout mouse. J Biol Chem. 2004;279:19149-56 pubmed
    ..This increased solubility of transducin would make it more susceptible to translocation from the outer segments. ..
  4. Craft C, Xu J, Slepak V, Zhan Poe X, Zhu X, Brown B, et al. PhLPs and PhLOPs in the phosducin family of G beta gamma binding proteins. Biochemistry. 1998;37:15758-72 pubmed
    ..The phosducin-like orphan proteins (PhLOPs) fail to bind Gbeta gamma, suggesting that the PhLOP isoforms may participate in still unidentified signaling pathways. ..
  5. Partridge J, Puhl H, Ikeda S. Phosducin and phosducin-like protein attenuate G-protein-coupled receptor-mediated inhibition of voltage-gated calcium channels in rat sympathetic neurons. Mol Pharmacol. 2006;70:90-100 pubmed
    ..Unlike other Gbetagamma sequestering proteins that abolish the short-term inhibition of Ca2+ channels, PDC and PDCL require prolonged agonist exposure before effects on modulation are realized. ..
  6. Song H, Belcastro M, Young E, Sokolov M. Compartment-specific phosphorylation of phosducin in rods underlies adaptation to various levels of illumination. J Biol Chem. 2007;282:23613-21 pubmed
    ..These results support the role of phosducin in regulating signaling in the rod outer segment compartment and suggest distinct functions for phosphorylation sites 54 and 71. ..
  7. Robatzek M, Niacaris T, Steger K, Avery L, Thomas J. eat-11 encodes GPB-2, a Gbeta(5) ortholog that interacts with G(o)alpha and G(q)alpha to regulate C. elegans behavior. Curr Biol. 2001;11:288-93 pubmed
    ..These interactions provide a mechanism for the modulation of behavior by antagonistic G protein networks. ..
  8. Hajdu Cronin Y, Chen W, Patikoglou G, Koelle M, Sternberg P. Antagonism between G(o)alpha and G(q)alpha in Caenorhabditis elegans: the RGS protein EAT-16 is necessary for G(o)alpha signaling and regulates G(q)alpha activity. Genes Dev. 1999;13:1780-93 pubmed
    ..elegans, and that G(o)alpha negatively regulates the G(q) pathway, possibly via EAT-16 or SAG-1. We propose that a major cellular role of G(o) is to antagonize signaling by G(q). ..
  9. Nakano K, Chen J, Tarr G, Yoshida T, Flynn J, Bitensky M. Rethinking the role of phosducin: light-regulated binding of phosducin to 14-3-3 in rod inner segments. Proc Natl Acad Sci U S A. 2001;98:4693-8 pubmed
    ..By dissociating the Pd/14-3-3 complex, light enables both proteins to function in this role. ..

More Information


  1. Zhu X, Craft C. The carboxyl terminal domain of phosducin functions as a transcriptional activator. Biochem Biophys Res Commun. 2000;270:504-9 pubmed
  2. Chase D, Patikoglou G, Koelle M. Two RGS proteins that inhibit Galpha(o) and Galpha(q) signaling in C. elegans neurons require a Gbeta(5)-like subunit for function. Curr Biol. 2001;11:222-31 pubmed
    ..The formation of RGS-Gbeta(5) complexes is required for the expression or stability of both the RGS and Gbeta(5) proteins. Appropriate RGS-Gbeta(5) complexes regulate both Galpha(o) and Galpha(q) proteins in vivo. ..
  3. Van Der Linden A, Simmer F, Cuppen E, Plasterk R. The G-protein beta-subunit GPB-2 in Caenorhabditis elegans regulates the G(o)alpha-G(q)alpha signaling network through interactions with the regulator of G-protein signaling proteins EGL-10 and EAT-16. Genetics. 2001;158:221-35 pubmed
    ..Taken together, our results suggest that GPB-2 works in concert with the RGS proteins EGL-10 and EAT-16 to regulate GOA-1 (G(o)alpha) and EGL-30 (G(q)alpha) signaling. ..
  4. Obin M, Lee B, Meinke G, Bohm A, Lee R, Gaudet R, et al. Ubiquitylation of the transducin betagamma subunit complex. Regulation by phosducin. J Biol Chem. 2002;277:44566-75 pubmed
    ..We conclude that Tbetagamma is a substrate of the ubiquitin-proteasome pathway and suggest that phosducin serves to protect Tbetagamma following the light-dependent dissociation of Talphabetagamma. ..
  5. Thulin C, Howes K, Driscoll C, Savage J, Rand T, Baehr W, et al. The immunolocalization and divergent roles of phosducin and phosducin-like protein in the retina. Mol Vis. 1999;5:40 pubmed
    ..Phosducin-like protein may have a role in regulating the processing of visual signals by the neural cells of the inner retina. ..
  6. Patikoglou G, Koelle M. An N-terminal region of Caenorhabditis elegans RGS proteins EGL-10 and EAT-16 directs inhibition of G(alpha)o versus G(alpha)q signaling. J Biol Chem. 2002;277:47004-13 pubmed
    ..We conclude that the N-terminal region directs inhibition of G(alpha) signaling by forming a complex with the GGL/RGS region and affecting its stability, membrane localization, and G(alpha) target specificity. ..
  7. Dekomien G, Epplen J. The canine Phosducin gene: characterization of the exon-intron structure and exclusion as a candidate gene for generalized progressive retinal atrophy in 11 dog breeds. Mol Vis. 2002;8:138-42 pubmed
    ..CONCLUSIONS PDC was excluded as a candidate gene for autosomal recessively (ar) transmitted gPRA in 11 of the 20 dog breeds investigated. ..
  8. Jackman T, Bauer A, Greenbaum E, Glaw F, Vences M. Molecular phylogenetic relationships among species of the Malagasy-Comoran gecko genus Paroedura (Squamata: Gekkonidae). Mol Phylogenet Evol. 2008;46:74-81 pubmed
    ..Our data demonstrate the phylogenetic utility of phosducin, a novel marker in squamate phylogenetics, at the intrageneric level. ..
  9. Kobayashi Y, Hisatomi O, Yamamoto S, Tokunaga F. Distribution of rod- and cone-specific phosducins in retinas of non-mammalian vertebrates. Comp Biochem Physiol B Biochem Mol Biol. 2002;133:77-83 pubmed
  10. Mattoo S, Lee Y, Dixon J. Interactions of bacterial effector proteins with host proteins. Curr Opin Immunol. 2007;19:392-401 pubmed
    ..This review highlights some of the common host proteins and signaling cascades targeted by such pathogens. ..
  11. van Soest S, te Nijenhuis S, van den Born L, Bleeker Wagemakers E, Sharp E, Sandkuijl L, et al. Fine mapping of the autosomal recessive retinitis pigmentosa locus (RP12) on chromosome 1q; exclusion of the phosducin gene (PDC). Cytogenet Cell Genet. 1996;73:81-5 pubmed
    ..Our data result in the following order of the markers and genes in the region 1q31 --> q32.1: cen-D1S158-(D1S238-D1S422)/PDC- D1S533-RP12/(F13B-D1S413)-CACNL1A3-DIS4 77-D1S306-D1S53-tel. ..
  12. Pyne S, Pyne N. Sphingosine 1-phosphate signalling via the endothelial differentiation gene family of G-protein-coupled receptors. Pharmacol Ther. 2000;88:115-31 pubmed
    ..Finally, we describe future directions for S1P research and novel approaches whereby S1P signalling can be manipulated for therapeutic intervention in disease. ..
  13. Chen F, Ng P, Faull K, Lee R. Cone photoreceptor betagamma-transducin: posttranslational modification and interaction with phosducin. Invest Ophthalmol Vis Sci. 2003;44:4622-9 pubmed
    ..Changes in Tbetagamma characteristics by Tgamma methylation reveal conformational changes on a surface domain that is essential for Tbetagamma functions and support a regulatory role for reversible methylation. ..
  14. Dockray G. Making sense of gut contents. Scand J Gastroenterol. 2003;38:451-5 pubmed
  15. Lukov G, Myung C, McIntire W, Shao J, Zimmerman S, Garrison J, et al. Role of the isoprenyl pocket of the G protein beta gamma subunit complex in the binding of phosducin and phosducin-like protein. Biochemistry. 2004;43:5651-60 pubmed
    ..These results support the structural model in which the prenyl group escapes contact with the aqueous milieu by inserting into the prenyl pocket and stabilizing the Pdc-binding conformation of Gbetagamma. ..
  16. Brown B, Carlson B, Zhu X, Lolley R, Craft C. Light-driven translocation of the protein phosphatase 2A complex regulates light/dark dephosphorylation of phosducin and rhodopsin. Biochemistry. 2002;41:13526-38 pubmed
    ..This light-driven PP2A translocation provides a potential mechanism for efficient dephosphorylation of two critical photoreceptor transduction proteins, cytosolic phosducin and membrane-bound rhodopsin, by the same enzyme. ..
  17. Joberty G, Perlungher R, Macara I. The Borgs, a new family of Cdc42 and TC10 GTPase-interacting proteins. Mol Cell Biol. 1999;19:6585-97 pubmed
    ..We propose that the Borg proteins function as negative regulators of Rho GTPase signaling. ..
  18. Peterson Y, Bernard M, Ma H, Hazard S, Graber S, Lanier S. Stabilization of the GDP-bound conformation of Gialpha by a peptide derived from the G-protein regulatory motif of AGS3. J Biol Chem. 2000;275:33193-6 pubmed
    ..The AGS3-GPR motif presents an opportunity for selective control of Gialpha- and Gbetagamma-regulated effector systems, and the GPR motif allows for alternative modes of signal input to G-protein signaling systems. ..
  19. Schulz R, Wehmeyer A, Schulz K. Visualizing preference of G protein-coupled receptor kinase 3 for the process of kappa-opioid receptor sequestration. Mol Pharmacol. 2002;61:1444-52 pubmed
    ..Comparing the effect of over-expressed GRK2 and GRK3 on sequestration of kappa-receptors, we conclude that GRK3 more strongly induces kappa-receptor internalization than GRK2. ..
  20. Sobierajska K, Fabczak H, Fabczak S. Phosducin interacts with the G-protein betagamma-dimer of ciliate protozoan Blepharisma japonicum upon illumination. J Exp Biol. 2007;210:4213-23 pubmed
    ..The results of this study provide additional detailed characterization of the functional properties of the ciliate Pdc. The likely functional role of Pdc in Blepharisma is discussed. ..
  21. Kozasa T. Regulation of G protein-mediated signal transduction by RGS proteins. Life Sci. 2001;68:2309-17 pubmed
    ..These results indicate that RGS proteins have far more diverse functions than acting simply as GAPs and the characterization of function of each RGS protein is crucial to understand the G protein signaling network in cells. ..
  22. Manzur M, Hamzah J, Ganss R. Modulation of g protein signaling normalizes tumor vessels. Cancer Res. 2009;69:396-9 pubmed publisher
    ..Here, we consider the implications of these findings, and how they contribute to enhancing our understanding of remodeling angiogenic vessels as means for improving anticancer therapies. ..
  23. Schulz R, Wehmeyer A, Murphy J, Schulz K. Phosducin, beta-arrestin and opioid receptor migration. Eur J Pharmacol. 1999;375:349-57 pubmed
    ..Drug-induced receptor phosphorylation appears of subordinate significance for receptor internalization. ..
  24. Kim K, Ogrydziak D. Yarrowia lipolytica SRP receptor alpha-subunit. Yeast. 2000;16:1243-52 pubmed
    ..The SRP101 sequence has been deposited in GenBank under Accession No. AF132597. ..
  25. Ide M, Lewis D. Altered cortical CDC42 signaling pathways in schizophrenia: implications for dendritic spine deficits. Biol Psychiatry. 2010;68:25-32 pubmed publisher
    ..Thus, altered CDC42 signaling via CDC42EP3 may perturb synaptic plasticity and contribute to the spine deficits observed in layer 3 pyramidal neurons in schizophrenia. ..
  26. Woolf P, Linderman J. An algebra of dimerization and its implications for G-protein coupled receptor signaling. J Theor Biol. 2004;229:157-68 pubmed
    ..Applications of this work to the development of a novel class of dimerization-modulating drugs are also discussed. ..
  27. Hirsch D, Pirone D, Burbelo P. A new family of Cdc42 effector proteins, CEPs, function in fibroblast and epithelial cell shape changes. J Biol Chem. 2001;276:875-83 pubmed
    ..These results suggest that CEPs act downstream of Cdc42 to induce actin filament assembly leading to cell shape changes. ..
  28. Neitzel K, Hepler J. Cellular mechanisms that determine selective RGS protein regulation of G protein-coupled receptor signaling. Semin Cell Dev Biol. 2006;17:383-9 pubmed
    ..Here, we discuss these findings and their implications for established models of GPCR signaling. ..
  29. Zhu X, Craft C. Interaction of phosducin and phosducin isoforms with a 26S proteasomal subunit, SUG1. Mol Vis. 1998;4:13 pubmed
    ..PhLOP1, a truncated amino-terminal splice variant of Phd, is the best candidate for the interaction with SUG1 among the four Phd isoforms studied, which suggests a potential function for PhLOP1. ..
  30. Hawes B, Touhara K, Kurose H, Lefkowitz R, Inglese J. Determination of the G beta gamma-binding domain of phosducin. A regulatable modulator of G beta gamma signaling. J Biol Chem. 1994;269:29825-30 pubmed
    ..This inhibitory effect is completely reversed by pretreatment of cells with dibutyryl cAMP, an activator of PKA. Thus, the binding of G beta gamma to phosducin can be regulated by PKA-phosphorylation in an intact cell model system. ..
  31. Schulz R, Wehmeyer A, Schulz K, Murphy J. Effect of phosducin on opioid receptor function. J Pharmacol Exp Ther. 1999;289:599-606 pubmed
    ..Finally, scavenging of Gbetagamma by Phd attenuates internalization of opioid receptors, which may contribute to the efficacy of opioids. ..
  32. Milligan G. High-content assays for ligand regulation of G-protein-coupled receptors. Drug Discov Today. 2003;8:579-85 pubmed
    ..Recent improvements in throughput using high-content screening platforms means that such assays are now an integral element of functional analysis in the drug discovery process. ..
  33. Turpaev K, Glatigny A, Bignon J, Delacroix H, Drapier J. Variation in gene expression profiles of human monocytic U937 cells exposed to various fluxes of nitric oxide. Free Radic Biol Med. 2010;48:298-305 pubmed publisher
    ..Finally, we showed that both (*)NO donors caused a marked decrease in phosphorylation of p70S6K, an mTOR substrate and regulator of mRNA translation, and protein kinase Akt, an upstream positive regulator of mTOR. ..
  34. Racchi M, Govoni S. The pharmacology of amyloid precursor protein processing. Exp Gerontol. 2003;38:145-57 pubmed
    ..More recently, these efforts have contributed to the characterization of the enzymes which regulate the formation of beta-amyloid. ..
  35. Bowers M, Hopf F, Chou J, Guillory A, Chang S, Janak P, et al. Nucleus accumbens AGS3 expression drives ethanol seeking through G betagamma. Proc Natl Acad Sci U S A. 2008;105:12533-8 pubmed publisher
    ..AGS3 up-regulation during abstinence may be a key determinant of the transition from social consumption to compulsion-like seeking during relapse. ..
  36. Kinoshita M, Field C, Coughlin M, Straight A, Mitchison T. Self- and actin-templated assembly of Mammalian septins. Dev Cell. 2002;3:791-802 pubmed
    ..We conclude that septins alone self-assemble into rings, that adaptor proteins recruit septins to actin bundles, and that septins help organize these bundles. ..
  37. Fabczak H, Sobierajska K, Fabczak S. Identification of possible phosducins in the ciliate Blepharisma japonicum. Protist. 2004;155:181-92 pubmed
  38. Hagiwara K, Wada A, Katadae M, Ito M, Ohya Y, Casey P, et al. Analysis of the molecular interaction of the farnesyl moiety of transducin through the use of a photoreactive farnesyl analogue. Biochemistry. 2004;43:300-9 pubmed
  39. Ruiz Gomez A, Humrich J, Murga C, Quitterer U, Lohse M, Mayor F. Phosphorylation of phosducin and phosducin-like protein by G protein-coupled receptor kinase 2. J Biol Chem. 2000;275:29724-30 pubmed
    ..The identification of phosducin and PhLP as new substrates for GRK2 further expands the cellular roles of this kinase and suggests new mechanisms for modulating GPCR signal transduction. ..
  40. Pedreno J, Hurt Camejo E, Wiklund O, Badimon L, Masana L. Low-density lipoprotein (LDL) binds to a G-protein coupled receptor in human platelets. Evidence that the proaggregatory effect induced by LDL is modulated by down-regulation of binding sites and desensitization of its mediated signaling. Atherosclerosis. 2001;155:99-112 pubmed
    ..This new regulatory mechanism may have implications for the thrombogenicity in hyperlipidemia and for effects of lipid lowering therapy. ..
  41. Kobayashi Y, Hisatomi O, Satoh T, Tokunaga F. Identification of rod- and cone-specific phosducins in teleost retinas. FEBS Lett. 2001;502:117-21 pubmed
    ..These results suggest that rod- and cone-specific PDs exist in teleost retinas, probably creating differences in light adaptation between rods and cones. ..
  42. Chang P, Yu J, Yu J. aflT, a MFS transporter-encoding gene located in the aflatoxin gene cluster, does not have a significant role in aflatoxin secretion. Fungal Genet Biol. 2004;41:911-20 pubmed
    ..The FadA-dependent G-protein signaling pathway previously shown to govern aflatoxin biosynthesis and sporulation plays a role in the regulation of aflT expression. ..
  43. Williams H, Schachner M, Wang B, Kenwrick S. Radiation hybrid mapping of the genes for tenascin-R (TNR), phosducin (PDC), laminin C1 (LAMC1), and TAX in 1q25-q32. Genomics. 1997;46:165-6 pubmed
  44. Gaudet R, Savage J, McLaughlin J, Willardson B, Sigler P. A molecular mechanism for the phosphorylation-dependent regulation of heterotrimeric G proteins by phosducin. Mol Cell. 1999;3:649-60 pubmed
    ..This transition disrupts phosducin's interface with Gt beta gamma, leading to the release of unencumbered Gt beta gamma, which reassociates with the membrane and Gt alpha to form a signaling-competent Gt alpha beta gamma heterotrimer. ..
  45. Perrino C, Rockman H. Reversal of cardiac remodeling by modulation of adrenergic receptors: a new frontier in heart failure. Curr Opin Cardiol. 2007;22:443-9 pubmed
    ..This review highlights some of the novel approaches to reverse pathological remodeling and improve cardiac dysfunction, placing emphasis on strategies targeting the adrenergic receptors. ..
  46. Conley P, Delaney S. Scientific and therapeutic insights into the role of the platelet P2Y12 receptor in thrombosis. Curr Opin Hematol. 2003;10:333-8 pubmed provide additional clinical benefit to patients with various cardiovascular diseases, especially those who may be aspirin-resistant. ..
  47. Myslivecek J. [Regulation of G-protein-coupled receptors]. Cesk Fysiol. 2003;52:4-9 pubmed
    ..In the basic scheme this regulations are comprehend as phosphorylation-based events. We discuss other possible pathways of receptor regulation in this review. ..
  48. Segev N. Ypt/rab gtpases: regulators of protein trafficking. Sci STKE. 2001;2001:re11 pubmed
    ..Finally, cross talk demonstrated among the various Ypt/Rabs, and between Ypt/Rabs and other signaling factors, suggests possible coordination among secretory steps, as well as between protein transport and other cellular processes. ..
  49. Rubinstein M, Peleg S, Berlin S, Brass D, Dascal N. Galphai3 primes the G protein-activated K+ channels for activation by coexpressed Gbetagamma in intact Xenopus oocytes. J Physiol. 2007;581:17-32 pubmed
    ..The Galphai3-induced enhancement of direct activation of GIRK by Gbetagamma, demonstrated here for the first time in intact cells, strongly supports the hypothesis that Galphai regulates GIRK gating under physiological conditions. ..
  50. Spik A, Oczkowski S, Olszak A, Formanowicz P, Błażewicz J, Jaruzelska J. Human fertility protein PUMILIO2 interacts in vitro with testis mRNA encoding Cdc42 effector 3 (CEP3). Reprod Biol. 2006;6:103-13 pubmed
    ..These results support the hypothesis that CEP3 mRNA may be a target of PUMILIO2 protein in the human male gonad and be under translational control mediated by specific nucleotide motifs within the 3'UTR. ..
  51. Hill C, Goddard A, Davey J, Ladds G. Investigating RGS proteins in yeast. Semin Cell Dev Biol. 2006;17:352-62 pubmed
  52. Chen J, Yoshida T, Nakano K, Bitensky M. Subcellular localization of phosducin in rod photoreceptors. Vis Neurosci. 2005;22:19-25 pubmed
    ..The functions of Pd in the ellipsoid and myoid regions remain unclear. The highest concentration of Pd was found at the rod synapse, consistent with a suggested role for Pd in the regulation of synaptic function. ..
  53. Oner S, Maher E, Breton B, Bouvier M, Blumer J. Receptor-regulated interaction of activator of G-protein signaling-4 and Galphai. J Biol Chem. 2010;285:20588-94 pubmed publisher
    ..These data suggest that AGS4-Galpha(i) complexes directly couple to a G-protein-coupled receptor and may serve as substrates for agonist-induced G-protein activation...