Skip to content Skip to navigation
University of Warwick
  • Study
  • |
  • Research
  • |
  • Business
  • |
  • Alumni
  • |
  • News
  • |
  • About

University of Warwick
Publications service & WRAP

Highlight your research

  • WRAP
    • Home
    • Search WRAP
    • Browse by Warwick Author
    • Browse WRAP by Year
    • Browse WRAP by Subject
    • Browse WRAP by Department
    • Browse WRAP by Funder
    • Browse Theses by Department
  • Publications Service
    • Home
    • Search Publications Service
    • Browse by Warwick Author
    • Browse Publications service by Year
    • Browse Publications service by Subject
    • Browse Publications service by Department
    • Browse Publications service by Funder
  • Statistics
  • Help & Advice
University of Warwick

The Library

  • Login

Regulators of G protein signalling proteins in the human myometrium

Tools
- Tools
+ Tools

Ladds, Graham , Zervou, Sevasti I., Vatish, Manu, Thornton, Steve and Davey, John . (2009) Regulators of G protein signalling proteins in the human myometrium. European Journal of Pharmacology, Vol.610 (No.1-3). pp. 23-28. ISSN 0014-2999

[img]
Preview
PDF
WRAP_ladds_9576638-130309-ladds_et_al._2009.pdf - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader

Download (340Kb)
Official URL: http://dx.doi.org/10.1016/j.ejphar.2009.03.042

Abstract

The contractile state of the human myometrium is controlled by extracellular signals that promote relaxation or contraction. Many of these signals function through G proteincoupled receptors at the cell surface, stimulating heterotrimeric G proteins and leading to changes in the activity of effector proteins responsible for bringing about the response. G proteins can interact with multiple receptors and many different effectors and are key players in the response. Regulators of G protein signalling (RGS) proteins are GTPase activating proteins for heterotrimeric G proteins and help terminate the signal. Little is known about the function of RGS proteins in human myometrium and we have therefore analysed transcript levels for RGS proteins at various stages of pregnancy (non-pregnant, preterm, term non-labouring, term labouring). RGS2 and RGS5 were the most abundantly expressed isolates in each of the patient groups. The levels of RGS4 and RGS16 (and to a lesser extent RGS2 and RGS14) increased in term labouring samples relative to the other groups. Yeast two-hybrid analysis and co-immunoprecipitation in myometrial cells revealed that both RGS2 and RGS5 interact directly with the cytoplasmic tail of the oxytocin receptor, suggesting they might help regulate signalling through this receptor. Key words: G protein-coupled receptors; labour; myometrium; RGS proteins

Item Type: Journal Article
Subjects: Q Science > QR Microbiology
Divisions: Faculty of Medicine > Warwick Medical School > Biomedical Cell Biology
Faculty of Medicine > Warwick Medical School > Clinical Sciences Research Institute (CSRI)
Faculty of Medicine > Warwick Medical School > Reproductive Health
Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH): G proteins, Cell receptors, Myometrium
Journal or Publication Title: European Journal of Pharmacology
Publisher: Elsevier BV
ISSN: 0014-2999
Date: 21 May 2009
Volume: Vol.610
Number: No.1-3
Number of Pages: 6
Page Range: pp. 23-28
Identification Number: 10.1016/j.ejphar.2009.03.042
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access
Funder: WellBeing (Organization), University Hospitals Coventry and Warwickshire NHS Trust
Grant number: 2198
References: Abramow-Newerly, M., Roy, A.A., Nunn, C., Chidiac, P. 2006. RGS proteins have a signalling complex: interactions between RGS proteins and GPCRs, effectors, and auxiliary proteins. Cell. Signal. 18, 579–591. Bansal, G., Druey, K.M., Xie, Z. 2007. R4 RGS proteins: Regulation of G-protein signaling and beyond. Pharmacol. Therap. 116, 473-495. Benians, A., Nobles, M., Hosny, S. Tinker, A. 2005. Regulators of G-protein signaling form a quaternary complex with the agonist, receptor, and G-protein. A novel explanation for the acceleration of signaling activation kinetics. J. Biol. Chem. 280, 13383-13394. Bernstein, L.S., Ramineni, S., Hague, C., Cladman, W., Chidiac, P., Levey, A.I., Hepler, J.R. 2004. RGS2 binds directly and selectively to the M1 muscarinic acetylcholine receptor third intracellular loop to modulate Gq/11α signaling. J. Biol. Chem. 279, 21248-21256. Blanks, A.M., Thornton, S. 2003. The role of oxytocin in parturition. BJOG 20, 46-51. Ballon, D.R., Flanary, P.L., Gladue, D.P., Konopka, J.B., Dohlman, H.G., Thorner, J. 2006. DEP-domain-mediated regulation of GPCR signaling responses. Cell. 126, 1079- 93. Brodt-Eppley, J., Myatt, L. 1999. Prostaglandin receptors in lower segment myometrium during gestation and labor. Obstet. Gynecol. 93, 89-93. Chatterjee, T.K., Eapen, A.K., Fisher, R.A. 1997. A truncated form of RGS3 negatively regulates G protein-coupled receptor stimulation of adenylyl cyclase and phosphoinositide phospholipase C. J. Biol. Chem. 272, 15481-15487. Cho, H., Harrison, K., Schwartz, O., Kehrl, J.H. 2003. The aorta and heart differentially express RGS (regulators of G-protein signalling) proteins that selectively regulate sphingosine 1-phosphate, angiotensin II and endothelin-1 signalling. Biochem. J. 371, 973-980. De Vries, L., Zheng, B., Fischer, T., Elenko, E., Farquhar, M.G. 2000. The regulator of G protein signaling family. Annu. Rev. Pharmacol. Toxicol. 40, 235-271. Dohlman, H.G., Song, J.P., Ma, D.R., Courchesne, W.E., Thorner, J. 1996. SST2, a negative regulator of pheromone signalling in the yeast Saccharomyces cerevisiae: expression, localisation and genetic interaction and physical association with GPA1 (the G protein α subunit). Mol. Cell. Biol. 16, 5194-5209. Druey, K.M., Blumer, K.J., Kang, V.H., Kehrl, J.H. 1996. Inhibition of G proteinmediated MAP kinase activation by members of a novel mammalian gene family. Nature 379, 742-746. Europe-Finner, G.N., Phaneuf, S., Cartwright, E., Mardon, H.J., López Bernal, A. 1997. Expression of human myometrial Gαs messenger ribonucleic acid transcript during pregnancy and labour: involvement of alternative splicing pathways. J. Mol. Endocrinol. 18, 15-25. Georgoussi, Z., Leontiadis, L., Mazarakou, G., Merkouris, M., Hyde, K., Hamm, H., 2006. Selective interactions between G protein subunits and RGS4 with the C-terminal domains of the mu- and delta-opioid receptors regulate opioid receptor signaling, Cell. Signal. 18, 771–782 Hague, C., Bernstein, L.S., Ramineni, S., Chen, Z., Minneman, K.P., Hepler, J.R. 2005. Selective inhibition of α1A-adrenergic receptor signaling by RGS2 association with the receptor third intracellular loop. J. Biol. Chem. 280, 27289-27295. Hao, J., Michalek, C., Zhang, W., Zhu, M., Xu, X., Mende, U. 2006. Regulation of cardiomyocyte signaling by RGS proteins: Differential selectivity towards G proteins and susceptibility to regulation. J. Mol. Cell. Cardiology 41, 51-61. Hill, C., Brownlie, Z., Davey, J., Milligan G., Ladds, G. 2008. Isolation and characterisationof a novel human RGS mutant displaying gain-of-function activity. Cell. Signal. 20, 323-336. Hepler, J.R. 2003. RGS protein and G protein interactions: a little help from their friends. Mol. Pharmacol. 64, 547–549. Hollinger, S., Hepler, J.R. 2002. Cellular regulation of RGS proteins: modulators and integrators of G protein signaling. Pharmacol. Rev. 54, 527-559. Hu, W., Li, F., Mahavadi. S., Murthy, K.S., 2008. Interleukin 1 up-regulates RGS4 through the canonical IKK2/kappaBα/NF-kappaB pathway in rabbit colonic smooth muscle. Biochem. J. 412, 35-43. Koelle, M.R., Horvitz, H.R. 1996. EGL-10 regulates G protein signaling in the C. elegans nervous system and shares a conserved domain with many mammalian proteins. Cell 84, 115-125. Ladds, G., Goddard, A., Hill, C., Thornton, S., Davey, J. 2007 Differential effects of RGS proteins on Gq and G11 activity. Cell. Signal. 19, 103-113. Langer, I., Tikhonova, I.G., Boulegue, C., Esteve, J.P., Vatinel, S., Ferrand, A., Moroder, L., Robberecht, P., Fourmy, D. 2008. Evidence for a direct and functional interaction between the regulators of G protein. doi:10.1124/mol.108.051607. signaling-2 and phosphorylated C-terminus of cholecystokinin-2 receptor Li, B. Fields, S. 1993. Identification of mutations in p53 that affect its binding to SV40 T antigen by using the yeast two-hybrid system. FASEB J. 7, 957-963. Lopez-Bernal, A.L., TambyRaja, R.L. 2000. Preterm Labour. Baillieres Best Pract. Res. Clin. Obstet. Gynaecol. 14, 133-153. Mittmann, C., Chung, C.H., Höppner, G., Michalek, C., Nose, M., Schüler, C., Schuh, A., Eschenhagen, T., Weil, J., Pieske, B., Hirt, S., Wieland, T. 2002. Expression of ten RGS proteins in human myocardium: functional characterization of an upregulation of RGS4 in heart failure. Cardiovasc. Res. 55, 778-786. Moore, S.D., Brodt-Eppley, J., Cornelison, L.M., Burk, S.E., Slater, D.M. Myatt, L. 1999. Expression of prostaglandin H synthase isoforms in human myometrium at parturition. Am. J. Obstet. Gynecol. 180, 103-109. Neitzel, K.L., Hepler, J.R. 2006. Cellular mechanisms that determine selective RGS protein regulation of G protein-coupled receptor signaling. Semin. Cell Dev. Biol. 17, 383-389. O’Brien, M., Morrison, J.J., Smith, T.J., 2008. Upregulation of PSCDBP, TLR2, TWIST1, FLJ35382, EDNRB and RGS12 gene expression in human myometrium at labor. Reprod. Sci. 15, 382-393. Park, E.S., Echetebu, C.O., Soloff, S., Soloff, M.S. 2002. Oxytocin stimulation of RGS2 mRNA expression in cultured human myometrial cells. Am. J. Physiol. Endocrinol. Metab. 282, E580-E584. Phaneuf, S., Europe-Finner, G.N., Carrasco, M.P., Hamilton, C.H., López Bernal, A. 1995. Oxytocin signalling in human myometrium. Adv. Exp. Med. Biol. 395, 453-467. Plested, C.P., Lopez-Bernal, A.L. 2001. Desensitisation of the oxytocin receptor and other G protein coupled receptors in the human myometrium. Exp. Physiol. 86, 303- 312. Ross, E.M., Wilkie, T.M. 2000. GTPase-activating proteins for heterotrimeric G proteins: regulators of G protein signaling (RGS) and RGS-like proteins. Annu. Rev. Biochem. 69, 795-827. Saitoh, O., Kubo, Y., Miyatani, Y., Assano, T., Nakata, H. 1997. RGS8 accelerates Gprotein- mediated modulation of K+ currents. Nature 390, 525-529. Sanborn, B., Qian, A., Ku, C., Wen, Y., Anwer, K., Monga, M., Singh, S. 1995. Mechanisms regulating oxytocin receptor coupling to phospholipase C in rat and human myometrium. Adv. Exp. Med. Biol. 395, 469-479. Snabaitis, A.K., Muntendorf, A., Wieland, T., Avkiran, M. 2005. Regulation of the extracellular signal-regulated kinase pathway in adult myocardium: differential roles of G(q/11), Gi and G(12/13) proteins in signalling by alpha1-adrenergic, endothelin-1 and thrombin-sensitive protease-activated receptors. Cell. Signal. 17, 655-664. Snow, B.E., Hall, R.A., Krumins, A.M., Brothers, G.M., Bouchard, D., Brothers, C.A., Chung, S., Mangion, J., Gilman, A.G., Lefkowitz, R.J., Siderovski, D.P. 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. Suarez, V.R., Park, E-S., Hankins, G.D.V., Soloff, M.S. 2003. Expression of regulator of G protein signaling-2 (RGS2) in rat myometrium during pregnancy and parturition. Am. J. Obstet. Gynecol. 188, 973-977. Tamirisa, P., Blumer, K.J., Muslin, A.J. 1999. RGS4 inhibits G-protein signaling in cardiomyocytes. Circulation 99, 441-447. Tang, K.M., Wang, G.R., Lu, P., Karas, R.H., Aronovitz, M., Heximer, S.P., Kaltenbronn K.M., Blumer, K.J., Siderovski, D.P., Zhu, Y., Mendelsohn, M.E. 2003. Regulator of G protein signaling-2 mediates vascular smooth muscle relaxation and blood pressure. Nature Medicine 12, 1506-1512. Tinker, A. 2006. The selective interactions and functions of regulators of G-protein signalling. Semin. Cell Dev. Biol. 17,377-382. Tribe, R.M., Moriaty, P., Poston, L. 2000. Calcium homeostatic pathways change with gestation in human myometrium. Biol. Reprod. 63, 748-755. Wang, Q., Liu, M., Mullah, B., Siderovski, D.P., Neubig, R.R. 2002. Receptor-selective effects of endogenous RGS3 and RGS5 to regulate mitogen-activated protein kinase activation in rat vascular smooth muscle cells. J. Biol. Chem. 277, 24949-24958. Willars, G.B. 2006. Mammalian RGS proteins: multifunctional regulators of cellular signaling. Semin. Cell Dev. Biol. 17, 363-376. Xie, G.X. Palmer, P.P. 2007. How regulators of G protein signaling achieve selective regulation. J. Mol. Biol. 366, 349-365. Xu, X., Zeng, W., Popov, S., Berman, D.M., Davignon, I., Yu, K., Yowe, D., Offermanns, S., Muallem, S., Wilkie, T.M. 1999. RGS proteins determine signaling specificity of Gq-coupled receptors. J. Biol. Chem. 274, 3549-3556. Zeng, W., Xu, X., Popov, S., Mukhopadhyay, S., Chidiac, P., Swistok, J., Danho, W., Yagaloff, K.A., Fisher, S.L., Ross, E.M., Muallem, S., Wilkie, T.M. 1998. The Nterminal domain of RGS4 confers receptor-selective inhibition of G protein signaling. J. Biol. Chem. 273, 34687-34690.
URI: http://wrap.warwick.ac.uk/id/eprint/486

Data sourced from Thomson Reuters' Web of Knowledge

Request changes to a record

Actions (login required)

View Item View Item

Document Downloads

More statistics for this item...
twitter

Email us: publications@warwick.ac.uk
Contact Details
About Us