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Gene Review

Gtpbp1  -  GTP binding protein 1

Mus musculus

Synonyms: AL022987, AW045683, C85212, G-protein 1, GP-1, ...
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Disease relevance of Gtpbp1


Psychiatry related information on Gtpbp1


High impact information on Gtpbp1

  • We also show that this locus can be subdivided into three regions, one of which contains Rgs2, which encodes a regulator of G protein signaling [11].
  • The G protein-coupled, receptor-activated phosphoinositide 3-kinase gamma (PI3Kgamma) mediates inflammatory responses and negatively controls cardiac contractility by reducing cAMP concentration [12].
  • One of the primary genes affected in HSCR encodes the G protein-coupled endothelin receptor-B (EDNRB) [13].
  • A new study shows that three such strains carry activating mutations in the genes encoding the G-protein subunits Galphaq or Galpha11, resulting in more pigment cell precursors and an excess of dermally retained pigment cells at birth [14].
  • These results explain in structural and chemical terms the basis of inward rectification, and they also have implications for G protein regulation of GIRK channels [15].

Chemical compound and disease context of Gtpbp1


Biological context of Gtpbp1


Anatomical context of Gtpbp1

  • G protein was detected within the endoplasmic reticulum, within smooth vesicles and stacks in the Golgi region and on the cell surface [16].
  • Besides Gi, membranes of neuronal tissues contain large amounts of Go, a G-protein with unknown function [2].
  • To address these issues, we have generated mutant mice lacking functional 5-HT2C receptors (previously termed 5-HT1C), prominent G-protein-coupled receptors that are widely expressed throughout the brain and spinal cord and which have been proposed to mediate numerous central nervous system (CNS) actions of serotonin [24].
  • Here we show that adrenaline suppresses B-cell electrical activity (and thus insulin secretion) by a G protein-dependent mechanism, which culminates in the activation of a sulphonylurea-insensitive low-conductance K+ channel distinct from the KATP channel [25].
  • A family of G-protein-coupled chemoattractant receptors is known to mediate the transport and activation of neutrophils and macrophages This family includes receptors for chemokines, such as interleukin-8, bacterial formylated peptides, platelet-activating factor, leukotriene B4, and the complement anaphylatoxins [26].

Associations of Gtpbp1 with chemical compounds


Physical interactions of Gtpbp1

  • Three cognate G protein-coupled receptors encoded by lpa(1)/lp(A1)/Edg-2/Gpcr26, lpa(2)/lp(A2)/Edg-4, and lpa(3)/lp(A3)/Edg-7 mediate the cellular effects of LPA [31].
  • Inhibitory and stimulatory regulation of Rac and cell motility by the G12/13-Rho and Gi pathways integrated downstream of a single G protein-coupled sphingosine-1-phosphate receptor isoform [32].
  • Regulation of serum response factor (SRF)-mediated gene transcription by G protein subunits and G protein-coupled receptors was investigated in transfected NIH3T3 cells and in a cell line that was derived from mice lacking Galphaq and Galpha11 [33].
  • Signaling from G protein-coupled receptors to c-Jun kinase involves beta gamma subunits of heterotrimeric G proteins acting on a Ras and Rac1-dependent pathway [34].
  • Targeted deletion of the G-protein-coupled endothelin receptors ET(A) and ET(B) was shown to result in characteristic developmental defects of derivatives of cephalic and cardiac neural crest and of neural crest-derived melanocytes and enteric neurons, respectively [35].

Enzymatic interactions of Gtpbp1


Regulatory relationships of Gtpbp1

  • To understand how the function of GIRK2 channels differs in these two mutant mice, we compared the G protein-activated inwardly rectifying K+ currents in cerebellar granule cells isolated from Girk2 null mutant and weaver mutant mice with those from wild-type mice [39].
  • These findings implicate abnormal betaAR-G protein coupling in the pathogenesis of the failing heart and point the way toward development of agents to inhibit betaARK1 as a novel mode of therapy [40].
  • When platelets from mice lacking the G protein-activated PI3Kgamma isoform were stimulated with ADP, aggregation was impaired [41].
  • Increased interleukin-6 production in mouse osteoblastic MC3T3-E1 cells expressing activating mutant of the stimulatory G protein [42].
  • G protein-activated K+ channel (GIRK) subunits possess a conserved extracellular integrin-binding motif (RGD) and bind directly to beta1 integrins [43].

Other interactions of Gtpbp1

  • Morphoregulatory activities of NCAM and N-cadherin can be accounted for by G protein-dependent activation of L- and N-type neuronal Ca2+ channels [44].
  • Heterozygous disruption of Gnas, the gene encoding the stimulatory G-protein alpha subunit (G(s)alpha), leads to distinct phenotypes depending on whether the maternal (m-/+) or paternal (+/p-) allele is disrupted [45].
  • Homer 2 tunes G protein-coupled receptors stimulus intensity by regulating RGS proteins and PLCbeta GAP activities [46].
  • By contrast, the G protein-gated inwardly rectifying current and possibly the agonist-independent basal current appeared to be less selective for K+ ions in weaver but not Girk2 null mutant granule cells [39].
  • GnRH stimulation of gonadotropin expression and secretion occurs through the G-protein-linked phospholipase C/inositol triphosphate intracellular signaling pathway, which ultimately leads to protein kinase C (PKC) activation and increased intracellular calcium levels [47].

Analytical, diagnostic and therapeutic context of Gtpbp1

  • The intracellular migration of G protein in vesicular stomatitis virus-infected cells was visualized by light and electron microscope radioautography after a 2-min pulse with [3H]mannose followed by nonradioactive chase for various intervals [48].
  • Pulse-chase experiments showed that oligosaccharide processing is impeded, and immunofluorescence localization revealed an accumulation of G protein in a juxtanuclear region that contains the Golgi complex [49].
  • The analgesia produced by inhibitory G protein-coupled receptor agonists involves coordinated postsynaptic inhibition via G protein-coupled inwardly rectifying potassium channels (GIRKs) and presynaptic inhibition of neurotransmitter release through regulation of voltage-gated Ca(2+) channels [50].
  • To examine the extent of diversity of the G protein family, we used the polymerase chain reaction to detect additional gene products in mouse brain and spermatid RNA that share these conserved regions [51].
  • Immunoprecipitation from ventricular myocytes using anti-Ca(v)1.2 or anti-caveolin-3 followed by Western blot analysis showed that caveolin-3, Ca(v)1.2, beta(2)-AR (not beta(1)-AR), G protein alpha(s), adenylyl cyclase, protein kinase A, and protein phosphatase 2a are closely associated [52].


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  12. PI3Kgamma modulates the cardiac response to chronic pressure overload by distinct kinase-dependent and -independent effects. Patrucco, E., Notte, A., Barberis, L., Selvetella, G., Maffei, A., Brancaccio, M., Marengo, S., Russo, G., Azzolino, O., Rybalkin, S.D., Silengo, L., Altruda, F., Wetzker, R., Wymann, M.P., Lembo, G., Hirsch, E. Cell (2004) [Pubmed]
  13. Spatiotemporal regulation of endothelin receptor-B by SOX10 in neural crest-derived enteric neuron precursors. Zhu, L., Lee, H.O., Jordan, C.S., Cantrell, V.A., Southard-Smith, E.M., Shin, M.K. Nat. Genet. (2004) [Pubmed]
  14. The G-netics of dark skin. Jackson, I.J. Nat. Genet. (2004) [Pubmed]
  15. Structural basis of inward rectification: cytoplasmic pore of the G protein-gated inward rectifier GIRK1 at 1.8 A resolution. Nishida, M., MacKinnon, R. Cell (2002) [Pubmed]
  16. The morphologic pathway of exocytosis of the vesicular stomatitis virus G protein in cultured fibroblasts. Wehland, J., Willingham, M.C., Gallo, M.G., Pastan, I. Cell (1982) [Pubmed]
  17. Antisense oligodeoxynucleotides to GS protein alpha-subunit sequence accelerate differentiation of fibroblasts to adipocytes. Wang, H.Y., Watkins, D.C., Malbon, C.C. Nature (1992) [Pubmed]
  18. Augmentation of antigen receptor-mediated responses by histamine H1 receptor signaling. Banu, Y., Watanabe, T. J. Exp. Med. (1999) [Pubmed]
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  22. Mu-opioid receptor desensitization by beta-arrestin-2 determines morphine tolerance but not dependence. Bohn, L.M., Gainetdinov, R.R., Lin, F.T., Lefkowitz, R.J., Caron, M.G. Nature (2000) [Pubmed]
  23. Role of G-protein-coupled adenosine receptors in downregulation of inflammation and protection from tissue damage. Ohta, A., Sitkovsky, M. Nature (2001) [Pubmed]
  24. Eating disorder and epilepsy in mice lacking 5-HT2c serotonin receptors. Tecott, L.H., Sun, L.M., Akana, S.F., Strack, A.M., Lowenstein, D.H., Dallman, M.F., Julius, D. Nature (1995) [Pubmed]
  25. Activation by adrenaline of a low-conductance G protein-dependent K+ channel in mouse pancreatic B cells. Rorsman, P., Bokvist, K., Ammälä, C., Arkhammar, P., Berggren, P.O., Larsson, O., Wåhlander, K. Nature (1991) [Pubmed]
  26. The C5a chemoattractant receptor mediates mucosal defence to infection. Höpken, U.E., Lu, B., Gerard, N.P., Gerard, C. Nature (1996) [Pubmed]
  27. Insulin action impaired by deficiency of the G-protein subunit G ialpha2. Moxham, C.M., Malbon, C.C. Nature (1996) [Pubmed]
  28. Motor deficit and impairment of synaptic plasticity in mice lacking mGluR1. Conquet, F., Bashir, Z.I., Davies, C.H., Daniel, H., Ferraguti, F., Bordi, F., Franz-Bacon, K., Reggiani, A., Matarese, V., Condé, F. Nature (1994) [Pubmed]
  29. Initiation of neuropathic pain requires lysophosphatidic acid receptor signaling. Inoue, M., Rashid, M.H., Fujita, R., Contos, J.J., Chun, J., Ueda, H. Nat. Med. (2004) [Pubmed]
  30. Normal p21N-ras couples bombesin and other growth factor receptors to inositol phosphate production. Wakelam, M.J., Davies, S.A., Houslay, M.D., McKay, I., Marshall, C.J., Hall, A. Nature (1986) [Pubmed]
  31. Characterization of lpa(2) (Edg4) and lpa(1)/lpa(2) (Edg2/Edg4) lysophosphatidic acid receptor knockout mice: signaling deficits without obvious phenotypic abnormality attributable to lpa(2). Contos, J.J., Ishii, I., Fukushima, N., Kingsbury, M.A., Ye, X., Kawamura, S., Brown, J.H., Chun, J. Mol. Cell. Biol. (2002) [Pubmed]
  32. Inhibitory and stimulatory regulation of Rac and cell motility by the G12/13-Rho and Gi pathways integrated downstream of a single G protein-coupled sphingosine-1-phosphate receptor isoform. Sugimoto, N., Takuwa, N., Okamoto, H., Sakurada, S., Takuwa, Y. Mol. Cell. Biol. (2003) [Pubmed]
  33. Specific involvement of G proteins in regulation of serum response factor-mediated gene transcription by different receptors. Mao, J., Yuan, H., Xie, W., Simon, M.I., Wu, D. J. Biol. Chem. (1998) [Pubmed]
  34. Signaling from G protein-coupled receptors to c-Jun kinase involves beta gamma subunits of heterotrimeric G proteins acting on a Ras and Rac1-dependent pathway. Coso, O.A., Teramoto, H., Simonds, W.F., Gutkind, J.S. J. Biol. Chem. (1996) [Pubmed]
  35. Characteristic defects in neural crest cell-specific Galphaq/Galpha11- and Galpha12/Galpha13-deficient mice. Dettlaff-Swiercz, D.A., Wettschureck, N., Moers, A., Huber, K., Offermanns, S. Dev. Biol. (2005) [Pubmed]
  36. Cloning, expression, and chromosomal localization of beta-adrenergic receptor kinase 2. A new member of the receptor kinase family. Benovic, J.L., Onorato, J.J., Arriza, J.L., Stone, W.C., Lohse, M., Jenkins, N.A., Gilbert, D.J., Copeland, N.G., Caron, M.G., Lefkowitz, R.J. J. Biol. Chem. (1991) [Pubmed]
  37. Hybrid transgenic mice reveal in vivo specificity of G protein-coupled receptor kinases in the heart. Eckhart, A.D., Duncan, S.J., Penn, R.B., Benovic, J.L., Lefkowitz, R.J., Koch, W.J. Circ. Res. (2000) [Pubmed]
  38. Mechanism of inhibition of adenylate cyclase by phospholipase C-catalyzed hydrolysis of phosphatidylcholine. Involvement of a pertussis toxin-sensitive G protein and protein kinase C. Diaz-Laviada, I., Larrodera, P., Nieto, J.L., Cornet, M.E., Diaz-Meco, M.T., Sanchez, M.J., Guddal, P.H., Johansen, T., Haro, A., Moscat, J. J. Biol. Chem. (1991) [Pubmed]
  39. Defective gamma-aminobutyric acid type B receptor-activated inwardly rectifying K+ currents in cerebellar granule cells isolated from weaver and Girk2 null mutant mice. Slesinger, P.A., Stoffel, M., Jan, Y.N., Jan, L.Y. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  40. Expression of a beta-adrenergic receptor kinase 1 inhibitor prevents the development of myocardial failure in gene-targeted mice. Rockman, H.A., Chien, K.R., Choi, D.J., Iaccarino, G., Hunter, J.J., Ross, J., Lefkowitz, R.J., Koch, W.J. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  41. Resistance to thromboembolism in PI3Kgamma-deficient mice. Hirsch, E., Bosco, O., Tropel, P., Laffargue, M., Calvez, R., Altruda, F., Wymann, M., Montrucchio, G. FASEB J. (2001) [Pubmed]
  42. Increased interleukin-6 production in mouse osteoblastic MC3T3-E1 cells expressing activating mutant of the stimulatory G protein. Motomura, T., Kasayama, S., Takagi, M., Kurebayashi, S., Matsui, H., Hirose, T., Miyashita, Y., Yamauchi-Takihara, K., Yamamoto, T., Okada, S., Kishimoto, T. J. Bone Miner. Res. (1998) [Pubmed]
  43. Expression of GIRK (Kir3.1/Kir3.4) channels in mouse fibroblast cells with and without beta1 integrins. Ivanina, T., Neusch, C., Li, Y.X., Tong, Y., Labarca, C., Mosher, D.F., Lester, H.A. FEBS Lett. (2000) [Pubmed]
  44. Morphoregulatory activities of NCAM and N-cadherin can be accounted for by G protein-dependent activation of L- and N-type neuronal Ca2+ channels. Doherty, P., Ashton, S.V., Moore, S.E., Walsh, F.S. Cell (1991) [Pubmed]
  45. Paternal versus maternal transmission of a stimulatory G-protein alpha subunit knockout produces opposite effects on energy metabolism. Yu, S., Gavrilova, O., Chen, H., Lee, R., Liu, J., Pacak, K., Parlow, A.F., Quon, M.J., Reitman, M.L., Weinstein, L.S. J. Clin. Invest. (2000) [Pubmed]
  46. Homer 2 tunes G protein-coupled receptors stimulus intensity by regulating RGS proteins and PLCbeta GAP activities. Shin, D.M., Dehoff, M., Luo, X., Kang, S.H., Tu, J., Nayak, S.K., Ross, E.M., Worley, P.F., Muallem, S. J. Cell Biol. (2003) [Pubmed]
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  48. Intracellular transport of the transmembrane glycoprotein G of vesicular stomatitis virus through the Golgi apparatus as visualized by electron microscope radioautography. Bergeron, J.J., Kotwal, G.J., Levine, G., Bilan, P., Rachubinski, R., Hamilton, M., Shore, G.C., Ghosh, H.P. J. Cell Biol. (1982) [Pubmed]
  49. Identification and characterization of a mouse cell mutant defective in the intracellular transport of glycoproteins. Tufaro, F., Snider, M.D., McKnight, S.L. J. Cell Biol. (1987) [Pubmed]
  50. Contribution of GIRK2-mediated postsynaptic signaling to opiate and alpha 2-adrenergic analgesia and analgesic sex differences. Mitrovic, I., Margeta-Mitrovic, M., Bader, S., Stoffel, M., Jan, L.Y., Basbaum, A.I. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
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  52. Localization of cardiac L-type Ca(2+) channels to a caveolar macromolecular signaling complex is required for beta(2)-adrenergic regulation. Balijepalli, R.C., Foell, J.D., Hall, D.D., Hell, J.W., Kamp, T.J. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
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