Advertisement

GPCRs

  • Angelika BöttgerEmail author
  • Ute Vothknecht
  • Cordelia Bolle
  • Alexander Wolf
Chapter
Part of the Learning Materials in Biosciences book series (LMB)

Abstract

G-protein-coupled receptors (GPCRs) as indicated by their name are coupled to trimeric G-proteins. Upon ligand binding to the receptor, the trimeric G-proteins dissociate into a Gα-subunit and a Gβ/γ-heterodimer. Both the α-subunit and the Gβ/γ-dimer then activate further signalling, for instance, by regulating the production of second messengers or the activity of ion channels. In the following we will discuss the history of the discovery of GPCR signalling, second messengers like cAMP and phospholipids and crucial target enzymes of these second messengers such as protein kinase A and protein kinase C.

References

  1. Blumberg PM (1988) Protein kinase C as the receptor for the phorbol ester tumor promoters: sixth Rhoads memorial award lecture. Cancer Res 48:1–8PubMedGoogle Scholar
  2. Caron MG, Srinivasan Y, Pitha J, Kociolek K, Lefkowitz RJ (1979) Affinity chromatography of the beta-adrenergic receptor. J Biol Chem 254:2923–2927PubMedGoogle Scholar
  3. Civelli O (2012) Orphan GPCRs and neuromodulation. Neuron 76:12–21CrossRefGoogle Scholar
  4. Conti M, Mika D, Richter W (2014) Cyclic AMP compartments and signaling specificity: role of cyclic nucleotide phosphodiesterases. J Gen Physiol 143:29–38CrossRefGoogle Scholar
  5. De Waard M, Hering J, Weiss N, Feltz A (2005) How do G proteins directly control neuronal Ca2+ channel function? Trends Pharmacol Sci 26:427–436CrossRefGoogle Scholar
  6. Dixon RA, Kobilka BK, Strader DJ, Benovic JL, Dohlman HG, Frielle T, Bolanowski MA, Bennett CD, Rands E, Diehl RE, Mumford RA, Slater EE, Sigal IS, Caron MG, Lefkowitz RJ, Strader CD (1986) Cloning of the gene and cDNA for mammalian beta-adrenergic receptor and homology with rhodopsin. Nature 321:75–79CrossRefGoogle Scholar
  7. Fredriksson R, Schioth HB (2005) The repertoire of G-protein-coupled receptors in fully sequenced genomes. Mol Pharmacol 67:1414–1425CrossRefGoogle Scholar
  8. Gurevich VV, Gurevich EV (2015) Arrestins: critical players in trafficking of many GPCRs. Prog Mol Biol Transl Sci 132:1–14CrossRefGoogle Scholar
  9. Hatley ME, Gilman AG, Sunahara RK (2002) Expression, purification, and assay of cytosolic (catalytic) domains of membrane-bound mammalian adenylyl cyclases. Methods Enzymol 345:127–140CrossRefGoogle Scholar
  10. Henderson R, Unwin PN (1975) Three-dimensional model of purple membrane obtained by electron microscopy. Nature 257:28–32CrossRefGoogle Scholar
  11. Ihara K, Umemura T, Katagiri I, Kitajima-Ihara T, Sugiyama Y, Kimura Y, Mukohata Y (1999) Evolution of the archaeal rhodopsins: evolution rate changes by gene duplication and functional differentiation. J Mol Biol 285:163–174CrossRefGoogle Scholar
  12. Kandel ER, Dudai Y, Mayford MR (2014) The molecular and systems biology of memory. Cell 157:163–186CrossRefGoogle Scholar
  13. Khan SM, Sleno R, Gora S, Zylbergold P, Laverdure JP, Labbe JC, Miller GJ, Hebert TE (2013) The expanding roles of Gbetagamma subunits in G protein-coupled receptor signaling and drug action. Pharmacol Rev 65:545–577CrossRefGoogle Scholar
  14. Kida S (2012) A functional role for CREB as a positive regulator of memory formation and LTP. Exp Neurobiol 21:136–140CrossRefGoogle Scholar
  15. Northup JK, Sternweis PC, Smigel MD, Schleifer LS, Ross EM, Gilman AG (1980) Purification of the regulatory component of adenylate cyclase. Proc Natl Acad Sci U S A 77:6516–6520CrossRefGoogle Scholar
  16. Oesterhelt D, Stoeckenius W (1971) Rhodopsin-like protein from the purple membrane of Halobacterium halobium. Nat New Biol 233:149–152CrossRefGoogle Scholar
  17. Quinn PG (2002) Mechanisms of basal and kinase-inducible transcription activation by CREB. Prog Nucleic Acid Res Mol Biol 72:269–305CrossRefGoogle Scholar
  18. Rall TW, Sutherland EW (1962) Adenyl cyclase. II. The enzymatically catalyzed formation of adenosine 3′,5′-phosphate and inorganic pyrophosphate from adenosine triphosphate. J Biol Chem 237:1228–1232PubMedGoogle Scholar
  19. Rodbell M, Jones AB, Chiappe de Cingolani GE, Birnbaumer L (1968) The actions of insulin and catabolic hormones on the plasma membrane of the fat cells. Recent Prog Horm Res 24:215–254PubMedGoogle Scholar
  20. Sugden PH, Clerk A (1997) Regulation of the ERK subgroup of MAP kinase cascades through G protein-coupled receptors. Cell Signal 9:337–351CrossRefGoogle Scholar
  21. Tao YX, Conn PM (2014) Chaperoning G protein-coupled receptors: from cell biology to therapeutics. Endocr Rev 35:602–647CrossRefGoogle Scholar
  22. Torres-Quesada O, Mayrhofer JE, Stefan E (2017) The many faces of compartmentalized PKA signalosomes. Cell Signal 37:1–11CrossRefGoogle Scholar
  23. Zhang YL, Wang RC, Cheng K, Ring BZ, Su L (2017) Roles of Rap1 signaling in tumor cell migration and invasion. Cancer Biol Med 14:90–99CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Angelika Böttger
    • 1
    Email author
  • Ute Vothknecht
    • 2
  • Cordelia Bolle
    • 3
  • Alexander Wolf
    • 4
  1. 1.Department Biology IILMU MunichPlanegg-MartinsriedGermany
  2. 2.IZMB-Plant Cell BiologyUniversity of BonnBonnGermany
  3. 3.Department Biology ILMU MunichPlanegg-MartinsriedGermany
  4. 4.Inst. Molecular Toxicology/PharmacologyHelmholtz Zentrum MünichNeuherbergGermany

Personalised recommendations