Display options
Cite
Kamato D, Thach L, Bernard R, et al. Structure, Function, Pharmacology, and Therapeutic Potential of the G Protein, Gα/q,11. Front Cardiovasc Med. 2015;2:14doi: 10.3389/fcvm.2015.00014.
Kamato, D., Thach, L., Bernard, R., Chan, V., Zheng, W., Kaur, H., Brimble, M., Osman, N., & Little, P. J. (2015). Structure, Function, Pharmacology, and Therapeutic Potential of the G Protein, Gα/q,11. Frontiers in cardiovascular medicine, 214. https://doi.org/10.3389/fcvm.2015.00014
Kamato, Danielle, et al. "Structure, Function, Pharmacology, and Therapeutic Potential of the G Protein, Gα/q,11." Frontiers in cardiovascular medicine vol. 2 (2015): 14. doi: https://doi.org/10.3389/fcvm.2015.00014
Kamato D, Thach L, Bernard R, Chan V, Zheng W, Kaur H, Brimble M, Osman N, Little PJ. Structure, Function, Pharmacology, and Therapeutic Potential of the G Protein, Gα/q,11. Front Cardiovasc Med. 2015 Mar 24;2:14. doi: 10.3389/fcvm.2015.00014. eCollection 2015. PMID: 26664886; PMCID: PMC4671355.
Copy Download .nbib Format: NLM
Share it on

Front Cardiovasc Med. 2015 Mar 24;2:14. doi: 10.3389/fcvm.2015.00014. eCollection 2015.

Structure, Function, Pharmacology, and Therapeutic Potential of the G Protein, Gα/q,11.

Frontiers in cardiovascular medicine

Danielle Kamato, Lyna Thach, Rebekah Bernard, Vincent Chan, Wenhua Zheng, Harveen Kaur, Margaret Brimble, Narin Osman, Peter J Little

Affiliations

  1. Discipline of Pharmacy, Diabetes Complications Group, School of Medical Sciences, Health Innovations Research Institute, RMIT University , Bundoora, VIC , Australia.
  2. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre , Guangzhou , China ; Faculty of Health Sciences, University of Macau , Macau , China.
  3. Department of Chemistry, University of Auckland , Auckland , New Zealand.

PMID: 26664886 PMCID: PMC4671355 DOI: 10.3389/fcvm.2015.00014

Abstract

G protein coupled receptors (GPCRs) are one of the major classes of cell surface receptors and are associated with a group of G proteins consisting of three subunits termed alpha, beta, and gamma. G proteins are classified into four families according to their α subunit; Gαi, Gαs, Gα12/13, and Gαq. There are several downstream pathways of Gαq of which the best known is upon activation via guanosine triphosphate (GTP), Gαq activates phospholipase Cβ, hydrolyzing phosphatidylinositol 4,5-biphosphate into diacylglycerol and inositol triphosphate and activating protein kinase C and increasing calcium efflux from the endoplasmic reticulum. Although G proteins, in particular, the Gαq/11 are central elements in GPCR signaling, their actual roles have not yet been thoroughly investigated. The lack of research of the role on Gαq/11 in cell biology is partially due to the obscure nature of the available pharmacological agents. YM-254890 is the most useful Gαq-selective inhibitor with antiplatelet, antithrombotic, and thrombolytic effects. YM-254890 inhibits Gαq signaling pathways by preventing the exchange of guanosine diphosphate for GTP. UBO-QIC is a structurally similar compound to YM-254890, which can inhibit platelet aggregation and cause vasorelaxation in rats. Many agents are available for the study of signaling downstream of Gαq/11. The role of G proteins could potentially represent a novel therapeutic target. This review will explore the range of pharmacological and molecular tools available for the study of the role of Gαq/11 in GPCR signaling.

Keywords: G proteins; GPCR; cell signaling; therapeutic targets; transactivation

References

  1. Nature. 1996 Feb 8;379(6565):557-60 - PubMed
  2. Mol Pharmacol. 2003 Jun;63(6):1256-72 - PubMed
  3. Biochem Biophys Res Commun. 1992 Mar 16;183(2):694-700 - PubMed
  4. J Biol Chem. 1995 Jan 13;270(2):503-6 - PubMed
  5. Proc Natl Acad Sci U S A. 2005 Jul 5;102(27):9493-8 - PubMed
  6. J Cardiovasc Pharmacol. 2010 Oct;56(4):360-8 - PubMed
  7. J Biol Chem. 2010 Aug 27;285(35):26798-805 - PubMed
  8. Nat Rev Mol Cell Biol. 2008 Jan;9(1):60-71 - PubMed
  9. Cell Mol Life Sci. 2005 Mar;62(5):551-77 - PubMed
  10. Endocrine. 2005 Feb;26(1):25-32 - PubMed
  11. ScientificWorldJournal. 2011 Mar 22;11:709-14 - PubMed
  12. Mol Pharmacol. 2000 May;57(5):976-83 - PubMed
  13. Biochim Biophys Acta. 1997 Jan 10;1355(1):81-8 - PubMed
  14. J Biol Chem. 2002 Jul 12;277(28):25707-14 - PubMed
  15. Proc Natl Acad Sci U S A. 1990 Dec;87(23):9113-7 - PubMed
  16. Endocrinology. 2013 Oct;154(10):3539-51 - PubMed
  17. J Virol. 2008 Sep;82(18):9191-205 - PubMed
  18. FASEB J. 1997 Apr;11(5):346-54 - PubMed
  19. Cell Mol Life Sci. 2015 Feb;72(4):799-808 - PubMed
  20. Cell Signal. 2009 Apr;21(4):551-8 - PubMed
  21. J Biol Chem. 2008 Oct 31;283(44):29888-96 - PubMed
  22. J Biol Chem. 2002 Oct 25;277(43):40789-98 - PubMed
  23. FASEB J. 2012 Aug;26(8):3473-82 - PubMed
  24. J Biol Chem. 2001 Sep 21;276(38):35883-90 - PubMed
  25. Biochem Biophys Res Commun. 2010 Jan 15;391(3):1330-5 - PubMed
  26. J Pineal Res. 2010 Oct;49(3):301-11 - PubMed
  27. Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12706-10 - PubMed
  28. Development. 2008 Feb;135(4):755-65 - PubMed
  29. J Biol Chem. 2013 Mar 8;288(10):7410-9 - PubMed
  30. Biochim Biophys Acta. 1980 Jul;599(2):623-38 - PubMed
  31. Biochim Biophys Acta. 2007 Apr;1768(4):994-1005 - PubMed
  32. J Biol Chem. 2002 Apr 5;277(14):11979-86 - PubMed
  33. Cell Signal. 2008 Oct;20(10):1900-10 - PubMed
  34. Vasc Health Risk Manag. 2005;1(3):199-208 - PubMed
  35. Mol Cell Biol. 2000 Sep;20(18):6837-48 - PubMed
  36. Chem Biol. 2013 Feb 21;20(2):146-59 - PubMed
  37. J Biol Chem. 2001 Jun 29;276(26):23945-53 - PubMed
  38. Acta Physiol (Oxf). 2007 May;190(1):9-19 - PubMed
  39. Endocrinology. 1993 Feb;132(2):524-9 - PubMed
  40. FEBS Lett. 1998 Dec 11;441(1):67-70 - PubMed
  41. Science. 2002 May 31;296(5573):1636-9 - PubMed
  42. J Vasc Surg. 2004 Mar;39(3):639-44 - PubMed
  43. J Biol Chem. 1998 Jan 16;273(3):1269-72 - PubMed
  44. Nature. 1988 May 12;333(6169):129-34 - PubMed
  45. J Biol Chem. 2003 May 2;278(18):15850-8 - PubMed
  46. Biosens Bioelectron. 2009 Mar 15;24(7):2298-304 - PubMed
  47. Physiol Rev. 1999 Oct;79(4):1373-430 - PubMed
  48. Mol Biol Cell. 2008 Jun;19(6):2520-33 - PubMed
  49. J Biol Chem. 2004 Nov 12;279(46):47438-45 - PubMed
  50. Br J Pharmacol. 2010 Jul;160(6):1295-301 - PubMed
  51. Thromb Haemost. 2003 Sep;90(3):406-13 - PubMed
  52. Life Sci. 2013 May 30;92(20-21):951-6 - PubMed
  53. J Biol Chem. 2006 Apr 14;281(15):10250-62 - PubMed
  54. Mol Pharmacol. 2005 Sep;68(3):670-9 - PubMed
  55. Pharmacol Toxicol. 1989 Sep;65(3):192-7 - PubMed
  56. J Biol Chem. 1999 Nov 19;274(47):33691-5 - PubMed
  57. Nat Med. 2008 Jan;14(1):64-8 - PubMed
  58. Am J Physiol Lung Cell Mol Physiol. 2009 Aug;297(2):L263-70 - PubMed
  59. EMBO J. 1997 Dec 1;16(23):7032-44 - PubMed
  60. Mol Cell Endocrinol. 2011 Jan 15;331(2):222-31 - PubMed
  61. Naunyn Schmiedebergs Arch Pharmacol. 2009 May;379(5):435-43 - PubMed
  62. PLoS One. 2012;7(6):e39066 - PubMed
  63. PLoS One. 2014 Jun 11;9(6):e99024 - PubMed
  64. Biochem J. 2006 Mar 15;394(Pt 3):557-62 - PubMed
  65. Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10049-53 - PubMed
  66. J Biol Chem. 2011 Apr 8;286(14):12407-16 - PubMed
  67. Exp Mol Med. 2014 Jun 20;46:e102 - PubMed
  68. J Biol Chem. 2003 May 16;278(20):17827-37 - PubMed
  69. J Antibiot (Tokyo). 2003 Apr;56(4):358-63 - PubMed
  70. Br J Pharmacol. 2014 Aug;171(16):3881-94 - PubMed
  71. Proc Natl Acad Sci U S A. 2010 Aug 3;107(31):13666-71 - PubMed
  72. Circ Res. 1999 May 28;84(10):1186-93 - PubMed
  73. Drug Metab Dispos. 2007 Jul;35(7):1017-22 - PubMed
  74. J Pharm Pharmacol. 2013 Apr;65(4):465-73 - PubMed
  75. Biochem Pharmacol. 2009 Mar 1;77(5):835-44 - PubMed
  76. Cell Signal. 2006 Feb;18(2):135-50 - PubMed
  77. Am J Physiol. 1994 May;266(5 Pt 1):C1421-31 - PubMed
  78. J Nat Med. 2013 Jan;67(1):196-201 - PubMed
  79. Biochem J. 1997 Jun 1;324 ( Pt 2):645-51 - PubMed
  80. PLoS One. 2010 Sep 23;5(9):e12964 - PubMed
  81. J Biol Chem. 2000 Jan 14;275(2):1327-36 - PubMed
  82. J Neuroimmunol. 2008 Sep 15;201-202:121-7 - PubMed
  83. J Biol Chem. 2005 Dec 2;280(48):40337-46 - PubMed
  84. Eur J Pharmacol. 1998 Apr 10;346(2-3):345-51 - PubMed
  85. Mol Pharmacol. 2000 Apr;57(4):700-8 - PubMed
  86. J Biol Chem. 2004 Feb 20;279(8):6701-10 - PubMed
  87. J Biol Chem. 2004 Dec 17;279(51):53643-52 - PubMed
  88. J Biol Chem. 2007 Mar 16;282(11):7833-43 - PubMed
  89. Nature. 1997 Sep 11;389(6647):183-6 - PubMed

Publication Types