Advertisement

cAMP guided his way: a life for G protein-mediated signal transduction and molecular pharmacology—tribute to Karl H. Jakobs

  • Klaus Aktories
  • Peter Gierschik
  • Dagmar Meyer zu Heringdorf
  • Martina Schmidt
  • Günter Schultz
  • Thomas WielandEmail author
Review Article
  • 2 Downloads

Abstract

Karl H. Jakobs, former editor-in-chief of Naunyn-Schmiedeberg’s Archives of Pharmacology and renowned molecular pharmacologist, passed away in April 2018. In this article, his scientific achievements regarding G protein-mediated signal transduction and regulation of canonical pathways are summarized. Particularly, the discovery of inhibitory G proteins for adenylyl cyclase, methods for the analysis of receptor-G protein interactions, GTP supply by nucleoside diphosphate kinases, mechanisms in phospholipase C and phospholipase D activity regulation, as well as the development of the concept of sphingosine-1-phosphate as extra- and intracellular messenger will presented. His seminal scientific and methodological contributions are put in a general and timely perspective to display and honor his outstanding input to the current knowledge in molecular pharmacology.

Keywords

Heterotrimeric G protein Low molecular mass GTP binding protein Adenylyl cyclase Phospholipase C Phospholipase D Calcium-dependent signaling Sphingosine-1-phoshate 

Abbreviations

A2AAR

adenosine receptor type 2A

ARF

ADP-ribosylation-factor

cAMP

cyclic AMP

[Ca2+]I

intracellular Ca2+ concentration

DHS

D,L-threo-dihydrosphingosine

DMS

N,N-dimethylsphingosine

Epac

exchange protein directly activated by cAMP

GAP

GTPase-activating protein

GEF

guanine nucleotide exchange factor

GPCR

G protein-coupled receptor

GppNHp

guanosine-5′-[(β,γ)-imido]triphosphate

GTPγS

guanosine-5′-[γ-thio]triphosphate

HL-60

human leukemia cell line

M2

M2 muscarinic acetylcholine receptor

M3

M3 muscarinic acetylcholine receptor

NDP

nucleoside diphosphate

NDPK

nucleoside diphosphate kinase

NEM

N-ethylmaleimide

NTP

nucleoside triphosphate

PA

phosphatidic acid

PGE1

prostaglandin E1

PIP2

phosphatidylinositol-4,5-bisphosphate

PIP5 kinase

phosphatidylinositol-4-phosphate-5-kinase

PMA

phorbol 12-myristate 13-acetate

PKA

protein kinase A

PKC

protein kinase C

PLC

phospholipase C

PLD

phospholipase D

PTX

pertussis toxin

RGS

regulator of G protein signaling

ROCK

Rho-dependent protein kinase

S1P

sphingosine-1-phosphate

SPC

sphingosylphosphorylcholine

SphK

sphingosine kinase

Notes

Author contribution

KA, PG, DM, MS, GS, and TW reviewed the literature and wrote the manuscript. All authors read and approved the manuscript.

Compliance with ethical standards

The authors declare that there are no conflicts of interest.

References

  1. Abu-Taha IH, Heijman J, Hippe HJ, Wolf NM, El-Armouche A, Nikolaev VO, Schafer M, Wurtz CM, Neef S, Voigt N, Baczko I, Varro A, Muller M, Meder B, Katus HA, Spiger K, Vettel C, Lehmann LH, Backs J, Skolnik EY, Lutz S, Dobrev D, Wieland T (2017) Nucleoside diphosphate kinase-C suppresses cAMP formation in human heart failure. Circulation 135:881–897CrossRefPubMedGoogle Scholar
  2. Aktories K (2011) Bacterial protein toxins that modify host regulatory GTPases. Nat Rev Microbiol 9:487–498CrossRefPubMedGoogle Scholar
  3. Aktories K, Jakobs KH (1981) Epinephrine inhibits adenylate cyclase and stimulates a GTPase in human platelet membranes via alpha-adrenoceptors. FEBS Lett 130:235–238CrossRefPubMedGoogle Scholar
  4. Aktories K, Jakobs KH (1984) Ni-Mediated inhibition of human platelet adenylate cyclase by thrombin. Eur J Biochem 145:333–338CrossRefPubMedGoogle Scholar
  5. Aktories K, Jakobs KH, Schultz G (1980a) Nicotinic acid inhibits adipocyte adenylate cyclase in a hormone-like manner. FEBS Lett 115:11–14CrossRefPubMedGoogle Scholar
  6. Aktories K, Schultz G, Jakobs KH (1979) Inhibition of hamster fat cell adenylate cyclase by prostaglandin e1 and epinephrine: requirement for GTP and sodium ions. FEBS Lett 107:100–104CrossRefPubMedGoogle Scholar
  7. Aktories K, Schultz G, Jakobs KH (1980b) Regulation of adenylate cyclase activity in hamster adipocytes. Inhibition by prostaglandins, α-adrenergic agonists and nicotinic acid. Naunyn Schmiedeberg's Arch Pharmacol 312:167–173CrossRefGoogle Scholar
  8. Aktories K, Schultz G, Jakobs KH (1982a) Cholera toxin inhibits prostaglandin E1 but not adrenaline-induced stimulation of GTP hydrolysis in human platelet membranes. FEBS Lett 146:65–68CrossRefPubMedGoogle Scholar
  9. Aktories K, Schultz G, Jakobs KH (1982b) Stimulation of a low Km GTPase by inhibitors of adipocyte adenylate cyclase. Mol Pharmacol 21:336–342PubMedGoogle Scholar
  10. Aktories K, Schultz G, Jakobs KH (1983a) Adenylate cyclase inhibition and GTPase stimulation by somatostatin in S49 lymphoma cyc variants are prevented by islet-activating protein. FEBS Lett 158:169–173CrossRefPubMedGoogle Scholar
  11. Aktories K, Schultz G, Jakobs KH (1983b) Islet-activating protein prevents nicotinic acid-induced GTPase stimulation and GTP but not GTPγS-induced adenylate cyclase inhibition in rat adipocytes. FEBS Lett 156:88–92CrossRefPubMedGoogle Scholar
  12. Alemany R, Kleuser B, Ruwisch L, Danneberg K, Lass H, Hashemi R, Spiegel S, Jakobs KH, Meyer zu Heringdorf D (2001) Depolarisation induces rapid and transient formation of intracellular sphingosine-1-phosphate. FEBS Lett 509:239–244CrossRefPubMedGoogle Scholar
  13. Alemany R, Meyer zu Heringdorf D, van Koppen CJ, Jakobs KH (1999) Formyl peptide receptor signaling in HL-60 cells through sphingosine kinase. J Biol Chem 274:3994–3999CrossRefPubMedGoogle Scholar
  14. Alemany R, Sichelschmidt B, Zu Heringdorf DM, Lass H, van Koppen CJ, Jakobs KH (2000) Stimulation of sphingosine-1-phosphate formation by the P2Y2 receptor in HL-60 cells: Ca2+ requirement and implication in receptor-mediated Ca2+ mobilization, but not MAP kinase activation. Mol Pharmacol 58:491–497CrossRefPubMedGoogle Scholar
  15. Asano T, Pedersen SE, Scott CW, Ross EM (1984) Reconstitution of catecholamine-stimulated binding of guanosine 5′-O-(3-thiotriphosphate) to the stimulatory GTP-binding protein of adenylate cyclase. Biochemistry 23:5460–5467CrossRefPubMedGoogle Scholar
  16. Attwood PV, Wieland T (2015) Nucleoside diphosphate kinase as protein histidine kinase. Naunyn Schmiedeberg's Arch Pharmacol 388:153–160CrossRefGoogle Scholar
  17. Baker MJ, Pan D, Welch HC (2016) Small GTPases and their guanine-nucleotide exchange factors and GTPase-activating proteins in neutrophil recruitment. Curr Opin Hematol 23:44–54CrossRefPubMedGoogle Scholar
  18. Bamburg JR (1999) Proteins of the ADF/cofilin family: essential regulators of actin dynamics. Annu Rev Cell Dev Biol 15:185–230CrossRefPubMedGoogle Scholar
  19. Bamburg JR (2011) Listeria monocytogenes cell invasion: a new role for cofilin in co-ordinating actin dynamics and membrane lipids. Mol Microbiol 81:851–854CrossRefPubMedGoogle Scholar
  20. Bauer D, Gupta D, Harotunian V, Meador-Woodruff JH, McCullumsmith RE (2008) Abnormal expression of glutamate transporter and transporter interacting molecules in prefrontal cortex in elderly patients with schizophrenia. Schizophr Res 104:108–120CrossRefPubMedPubMedCentralGoogle Scholar
  21. Beavo JA, Brunton LL (2002) Cyclic nucleotide research—still expanding after half a century. Nat Rev Mol Cell Biol 3:710–718CrossRefPubMedGoogle Scholar
  22. Bernstein BW, Bamburg JR (2010) ADF/cofilin: a functional node in cell biology. Trends Cell Biol 20:187–195CrossRefPubMedPubMedCentralGoogle Scholar
  23. Birnbaumer L, Brown AM (1987) G protein opening of K+ channels. Nature 327:21–22CrossRefPubMedGoogle Scholar
  24. Bischoff A, Czyborra P, Fetscher C, Meyer zu Heringdorf D, Jakobs KH, Michel MC (2000a) Sphingosine-1-phosphate and sphingosylphosphorylcholine constrict renal and mesenteric microvessels in vitro. Br J Pharmacol 130:1871–1877CrossRefPubMedPubMedCentralGoogle Scholar
  25. Bischoff A, Czyborra P, Meyer zu Heringdorf D, Jakobs KH, Michel MC (2000b) Sphingosine-1-phosphate reduces rat renal and mesenteric blood flow in vivo in a pertussis toxin-sensitive manner. Br J Pharmacol 130:1878–1883CrossRefPubMedPubMedCentralGoogle Scholar
  26. Bischoff A, Meyer zu Heringdorf D, Jakobs KH, Michel MC (2001) Lysosphingolipid receptor-mediated diuresis and natriuresis in anaesthetized rats. Br J Pharmacol 132:1925–1933CrossRefPubMedPubMedCentralGoogle Scholar
  27. Blaho VA, Hla T (2014) An update on the biology of sphingosine 1-phosphate receptors. J Lipid Res 55:1596–1608CrossRefPubMedPubMedCentralGoogle Scholar
  28. Blank JL, Brattain KA, Exton JH (1992) Activation of cytosolic phosphoinositide phospholipase C by G-protein βγ subunits. J Biol Chem 267:23069–23075PubMedGoogle Scholar
  29. Blankenbach KV, Schwalm S, Pfeilschifter J, Meyer zu Heringdorf D (2016) Sphingosine-1-phosphate receptor-2 antagonists: therapeutic potential and potential risks. Front Pharmacol 7:167CrossRefPubMedPubMedCentralGoogle Scholar
  30. Blomquist A, Schworer G, Schablowski H, Psoma A, Lehnen M, Jakobs KH, Rümenapp U (2000) Identification and characterization of a novel Rho-specific guanine nucleotide exchange factor. Biochem J 352(Pt 2):319–325CrossRefPubMedPubMedCentralGoogle Scholar
  31. Bokoch GM, Katada T, Northup JK, Ui M, Gilman AG (1984) Purification and properties of the inhibitory guanine nucleotide-binding regulatory component of adenylate cyclase. J Biol Chem 259:3560–3567PubMedGoogle Scholar
  32. Bond RA, Ijzerman AP (2006) Recent developments in constitutive receptor activity and inverse agonism, and their potential for GPCR drug discovery. Trends Pharmacol Sci 27:92–96CrossRefPubMedGoogle Scholar
  33. Boyer JL, Waldo GL, Harden TK (1992) βγ-Subunit activation of G-protein-regulated phospholipase C. J Biol Chem 267:25451–25456PubMedGoogle Scholar
  34. Brasier DJ (2017) Three scientific controversies to engage students in reading primary literature. J Undergrad Neurosci Educ: JUNE: a Publication of FUN, Faculty for Undergraduate Neuroscience 16:R13–R19Google Scholar
  35. Brinkmann V, Billich A, Baumruker T, Heining P, Schmouder R, Francis G, Aradhye S, Burtin P (2010) Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis. Nat Rev Drug Discov 9:883–897CrossRefGoogle Scholar
  36. Brown HA, Thomas PG, Lindsley CW (2017) Targeting phospholipase D in cancer, infection and neurodegenerative disorders. Nat Rev Drug Discov 16:351–367CrossRefPubMedPubMedCentralGoogle Scholar
  37. Bünemann M, Brandts B, zu Heringdorf DM, van Koppen CJ, Jakobs KH, Pott L (1995) Activation of muscarinic K+ current in guinea-pig atrial myocytes by sphingosine-1-phosphate. J Physiol 489(Pt 3):701–707CrossRefPubMedPubMedCentralGoogle Scholar
  38. Bunney TD, Katan M (2006) Phospholipase C ε: linking second messengers and small GTPases. Trends Cell Biol 16:640–648CrossRefPubMedGoogle Scholar
  39. Bustelo XR (2014) Vav family exchange factors: an integrated regulatory and functional view. Small GTPases 5:9CrossRefPubMedGoogle Scholar
  40. Calo LA, Davis PA, Pagnin E, Dal Maso L, Maiolino G, Seccia TM, Pessina AC, Rossi GP (2014) Increased level of p63RhoGEF and RhoA/Rho kinase activity in hypertensive patients. J Hypertens 32:331–338CrossRefPubMedGoogle Scholar
  41. Camps M (1994) Hot papers: biochemist Montserrat Camps discusses her paper on the regulation of phosphoinositide-specific phospholipase C by signal-transducing G-proteins. Scientist 8:16Google Scholar
  42. Camps M, Carozzi A, Schnabel P, Scheer A, Parker PJ, Gierschik P (1992a) Isozyme-selective stimulation of phospholipase C-β 2 by G protein βγ-subunits. Nature 360:684–686CrossRefPubMedGoogle Scholar
  43. Camps M, Hou C, Sidiropoulos D, Stock JB, Jakobs KH, Gierschik P (1992b) Stimulation of phospholipase C by guanine-nucleotide-binding protein βγ subunits. Eur J Biochem 206:821–831CrossRefPubMedGoogle Scholar
  44. Carbajo-Lozoya J, Lutz S, Feng Y, Kroll J, Hammes HP, Wieland T (2012) Angiotensin II modulates VEGF-driven angiogenesis by opposing effects of type 1 and type 2 receptor stimulation in the microvascular endothelium. Cell Signal 24:1261–1269CrossRefGoogle Scholar
  45. Cassel D, Selinger Z (1976) Catecholamine-stimulated GTPase activity in turkey erythrocyte membranes. Biochim Biophys Acta 452:538–551CrossRefPubMedGoogle Scholar
  46. Cassel D, Selinger Z (1977a) Catecholamine-induced release of [3H]-Gpp(NH)p from turkey erythrocyte adenylate cyclase. J Cyclic Nucleotide Res 3:11–22PubMedGoogle Scholar
  47. Cassel D, Selinger Z (1977b) Mechanism of adenylate cyclase activation by cholera toxin: inhibition of GTP hydrolysis at the regulatory site. Proc Natl Acad Sci U S A 74:3307–3311CrossRefPubMedPubMedCentralGoogle Scholar
  48. Cechova K, Hlouskova M, Javorkova E, Roubalova L, Ujcikova H, Holan V, Svoboda P (2018) Up-regulation of μ-, δ- and κ-opioid receptors in concanavalin A-stimulated rat spleen lymphocytes. J Neuroimmunol 321:12–23CrossRefPubMedGoogle Scholar
  49. Chakraborti S, Roy S, Mandal A, Chowdhury A, Chakraborti T (2013) Role of PKC-ξ in NADPH oxidase-PKC-α - Giα axis dependent inhibition of β-adrenergic response by U46619 in pulmonary artery smooth muscle cells. Arch Biochem Biophys 540:133–144CrossRefPubMedGoogle Scholar
  50. Chan H, Pitson SM (2013) Post-translational regulation of sphingosine kinases. Biochim Biophys Acta 1831:147–156CrossRefPubMedGoogle Scholar
  51. Chang YJ, Pownall S, Jensen TE, Mouaaz S, Foltz W, Zhou L, Liadis N, Woo M, Hao Z, Dutt P, Bilan PJ, Klip A, Mak T, Stambolic V (2015) The Rho-guanine nucleotide exchange factor PDZ-RhoGEF governs susceptibility to diet-induced obesity and type 2 diabetes. eLife 4:e06011CrossRefPubMedPubMedCentralGoogle Scholar
  52. Chen H, Bernstein BW, Bamburg JR (2000) Regulating actin-filament dynamics in vivo. Trends Biochem Sci 25:19–23CrossRefPubMedGoogle Scholar
  53. Chu J, Zheng H, Zhang YH, Loh HH, Law PY (2010) Agonist-dependent μ-opioid receptor signaling can lead to heterologous desensitization. Cell Signal 22:684–696CrossRefPubMedPubMedCentralGoogle Scholar
  54. Citri Y, Schramm M (1982) Probing of the coupling site of the β-adrenergic receptor. Competition between different forms of the guanyl nucleotide binding protein for interaction with the receptor. J Biol Chem 257:13257–13262PubMedGoogle Scholar
  55. Claas RF, ter Braak M, Hegen B, Hardel V, Angioni C, Schmidt H, Jakobs KH, Van Veldhoven PP, Meyer zu Heringdorf D (2010) Enhanced Ca2+ storage in sphingosine-1-phosphate lyase-deficient fibroblasts. Cell Signal 22:476–483CrossRefPubMedGoogle Scholar
  56. Cockcroft S (2001) Signalling roles of mammalian phospholipase D1 and D2. Cell Mol Life Sci: CMLS 58:1674–1687CrossRefPubMedGoogle Scholar
  57. Costa T, Herz A (1989) Antagonists with negative intrinsic activity at δ opioid receptors coupled to GTP-binding proteins. Proc Natl Acad Sci U S A 86:7321–7325CrossRefPubMedPubMedCentralGoogle Scholar
  58. Costa T, Lang J, Gless C, Herz A (1990) Spontaneous association between opioid receptors and GTP-binding regulatory proteins in native membranes: specific regulation by antagonists and sodium ions. Mol Pharmacol 37:383–394PubMedGoogle Scholar
  59. Cuello F, Schulze RA, Heemeyer F, Meyer HE, Lutz S, Jakobs KH, Niroomand F, Wieland T (2003) Activation of heterotrimeric G proteins by a high energy phosphate transfer via nucleoside diphosphate kinase (NDPK) B and Gβ subunits. Complex formation of NDPK B with Gβγ dimers and phosphorylation of His-266 in Gβ. J Biol Chem 278:7220–7226CrossRefPubMedGoogle Scholar
  60. de la Pena P, del Camino D, Pardo LA, Dominguez P, Barros F (1995) Gs couples thyrotropin-releasing hormone receptors expressed in Xenopus oocytes to phospholipase C. J Biol Chem 270:3554–3559CrossRefPubMedGoogle Scholar
  61. de Rooij J, Zwartkruis FJ, Verheijen MH, Cool RH, Nijman SM, Wittinghofer A, Bos JL (1998) Epac is a Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP. Nature 396:474–477CrossRefPubMedGoogle Scholar
  62. Del Galdo S, Vettel C, Heringdorf DM, Wieland T (2013) The activation of RhoC in vascular endothelial cells is required for the S1P receptor type 2-induced inhibition of angiogenesis. Cell Signal 25:2478–2484CrossRefPubMedGoogle Scholar
  63. Dhanasekaran N, Dermott JM (1996) Signaling by the G12 class of G proteins. Cell Signal 8:235–245CrossRefPubMedGoogle Scholar
  64. Draper-Joyce CJ, Verma RK, Michino M, Shonberg J, Kopinathan A, Klein Herenbrink C, Scammells PJ, Capuano B, Abramyan AM, Thal DM, Javitch JA, Christopoulos A, Shi L, Lane JR (2018) The action of a negative allosteric modulator at the dopamine D2 receptor is dependent upon sodium ions. Sci Rep 8:1208CrossRefPubMedPubMedCentralGoogle Scholar
  65. Dusaban SS, Brown JH (2015) PLCε mediated sustained signaling pathways. Adv Biol Regul 57:17–23CrossRefPubMedGoogle Scholar
  66. Evellin S, Nolte J, Tysack K, Vom Dorp F, Thiel M, Weernink PA, Jakobs KH, Webb EJ, Lomasney JW, Schmidt M (2002) Stimulation of phospholipase C-ε by the M3 muscarinic acetylcholine receptor mediated by cyclic AMP and the GTPase Rap2B. J Biol Chem 277:16805–16813CrossRefPubMedGoogle Scholar
  67. Exton JH (2002) Phospholipase D-structure, regulation and function. Rev Physiol Biochem Pharmacol 144:1–94CrossRefPubMedGoogle Scholar
  68. Fahimi-Vahid M, Gosau N, Michalek C, Han L, Jakobs KH, Schmidt M, Roberts N, Avkiran M, Wieland T (2002) Distinct signaling pathways mediate cardiomyocyte phospholipase D stimulation by endothelin-1 and thrombin. J Mol Cell Cardiol 34:441–453CrossRefPubMedGoogle Scholar
  69. Fazal L, Laudette M, Paula-Gomes S, Pons S, Conte C, Tortosa F, Sicard P, Sainte-Marie Y, Bisserier M, Lairez O, Lucas A, Roy J, Ghaleh B, Fauconnier J, Mialet-Perez J, Lezoualc'h F (2017) Multifunctional mitochondrial epac1 controls myocardial cell death. Circ Res 120:645–657CrossRefPubMedGoogle Scholar
  70. Frohman MA (2015) The phospholipase D superfamily as therapeutic targets. Trends Pharmacol Sci 36:137–144CrossRefPubMedPubMedCentralGoogle Scholar
  71. Gachet C, Cazenave JP, Ohlmann P, Hilf G, Wieland T, Jakobs KH (1992a) ADP receptor-induced activation of guanine-nucleotide-binding proteins in human platelet membranes. Eur J Biochem 207:259–263CrossRefPubMedGoogle Scholar
  72. Gachet C, Savi P, Ohlmann P, Maffrand JP, Jakobs KH, Cazenave JP (1992b) ADP receptor induced activation of guanine nucleotide binding proteins in rat platelet membranes—an effect selectively blocked by the thienopyridine clopidogrel. Thromb Haemost 68:79–83CrossRefPubMedGoogle Scholar
  73. Gado F, Di Cesare Mannelli L, Lucarini E, Bertini S, Cappelli E, Digiacomo M, Stevenson LA, Macchia M, Tuccinardi T, Ghelardini C, Pertwee RG, Manera C (2018) Identification of the first synthetic allosteric modulator of the CB2 receptors and evidence of its efficacy for neuropathic pain relief. J Med ChemGoogle Scholar
  74. Ghosh TK, Bian J, Gill DL (1994) Sphingosine 1-phosphate generated in the endoplasmic reticulum membrane activates release of stored calcium. J Biol Chem 269:22628–22635PubMedGoogle Scholar
  75. Gierschik P (1992) ADP-ribosylation of signal-transducing guanine nucleotide-binding proteins by pertussis toxin. Curr Top Microbiol Immunol 175:69–96PubMedGoogle Scholar
  76. Gierschik P, Bouillon T, Jakobs KH (1994) Receptor-stimulated hydrolysis of guanosine 5′-triphosphate in membrane preparations. Methods Enzymol 237:13–26CrossRefPubMedGoogle Scholar
  77. Gierschik P, Falloon J, Milligan G, Pines M, Gallin JI, Spiegel A (1986) Immunochemical evidence for a novel pertussis toxin substrate in human neutrophils. J Biol Chem 261:8058–8062PubMedGoogle Scholar
  78. Gierschik P, Jakobs KH (1987) Receptor-mediated ADP-ribosylation of a phospholipase C-stimulating G protein. FEBS Lett 224:219–223CrossRefPubMedGoogle Scholar
  79. Gierschik P, McLeish K, Jakobs KH (1988) Regulation of G-protein-mediated signal transfer by ions. J Cardiovasc Pharmacol 12(Suppl 5):S20–S24CrossRefPubMedGoogle Scholar
  80. Gierschik P, Moghtader R, Straub C, Dieterich K, Jakobs KH (1991) Signal amplification in HL-60 granulocytes. Evidence that the chemotactic peptide receptor catalytically activates guanine-nucleotide-binding regulatory proteins in native plasma membranes. Eur J Biochem 197:725–732CrossRefPubMedGoogle Scholar
  81. Gierschik P, Sidiropoulos D, Jakobs KH (1989a) Two distinct Gi-proteins mediate formyl peptide receptor signal transduction in human leukemia (HL-60) cells. J Biol Chem 264:21470–21473PubMedGoogle Scholar
  82. Gierschik P, Sidiropoulos D, Steisslinger M, Jakobs KH (1989b) Na+ regulation of formyl peptide receptor-mediated signal transduction in HL 60 cells. Evidence that the cation prevents activation of the G-protein by unoccupied receptors. Eur J Pharmacol 172:481–492CrossRefPubMedGoogle Scholar
  83. Gierschik P, Steisslinger M, Sidiropoulos D, Herrmann E, Jakobs KH (1989c) Dual Mg2+ control of formyl-peptide-receptor--G-protein interaction in HL 60 cells. Evidence that the low-agonist-affinity receptor interacts with and activates the G-protein. Eur J Biochem 183:97–105CrossRefPubMedGoogle Scholar
  84. Gilles AM, Presecan E, Vonica A, Lascu I (1991) Nucleoside diphosphate kinase from human erythrocytes. Structural characterization of the two polypeptide chains responsible for heterogeneity of the hexameric enzyme. J Biol Chem 266:8784–8789Google Scholar
  85. Gosau N, Fahimi-Vahid M, Michalek C, Schmidt M, Wieland T (2002) Signalling components involved in the coupling of α1-adrenoceptors to phospholipase D in neonatal rat cardiac myocytes. Naunyn Schmiedeberg's Arch Pharmacol 365:468–476CrossRefGoogle Scholar
  86. Grandoch M, Bujok V, Fleckenstein D, Schmidt M, Fischer JW, Weber AA (2009a) Epac inhibits apoptosis of human leukocytes. J Leukoc Biol 86:847–849CrossRefPubMedGoogle Scholar
  87. Grandoch M, Roscioni SS, Schmidt M (2010) The role of Epac proteins, novel cAMP mediators, in the regulation of immune, lung and neuronal function. Br J Pharmacol 159:265–284CrossRefPubMedGoogle Scholar
  88. Grandoch M, Rose A, ter Braak M, Jendrossek V, Rubben H, Fischer JW, Schmidt M, Weber AA (2009b) Epac inhibits migration and proliferation of human prostate carcinoma cells. Br J Cancer 101:2038–2042CrossRefPubMedPubMedCentralGoogle Scholar
  89. Grandt R, Aktories K, Jakobs KH (1986) Evidence for two GTPases activated by thrombin in membranes of human platelets. Biochem J 237:669–674CrossRefPubMedPubMedCentralGoogle Scholar
  90. Hackenthal E, Aktories K, Jakobs KH (1985) Mode of inhibition of renin release by angiotensin II. J Hypertens Suppl: Official Journal of the International Society of Hypertension 3:S263–S265Google Scholar
  91. Halls ML, Cooper DMF (2017) Adenylyl cyclase signalling complexes—pharmacological challenges and opportunities. Pharmacol Ther 172:171–180CrossRefPubMedGoogle Scholar
  92. Han L, Stope MB, de Jesus ML, Oude Weernink PA, Urban M, Wieland T, Rosskopf D, Mizuno K, Jakobs KH, Schmidt M (2007) Direct stimulation of receptor-controlled phospholipase D1 by phospho-cofilin. EMBO J 26:4189–4202CrossRefPubMedPubMedCentralGoogle Scholar
  93. Han X, Yu R, Ji L, Zhen D, Tao S, Li S, Sun Y, Huang L, Feng Z, Li X, Han G, Schmidt M, Han L (2011a) InlB-mediated Listeria monocytogenes internalization requires a balanced phospholipase D activity maintained through phospho-cofilin. Mol Microbiol 81:860–880CrossRefPubMedGoogle Scholar
  94. Han X, Yu R, Zhen D, Tao S, Schmidt M, Han L (2011b) β-1,3-Glucan-induced host phospholipase D activation is involved in Aspergillus fumigatus internalization into type II human pneumocyte A549 cells. PLoS One 6:e21468CrossRefPubMedPubMedCentralGoogle Scholar
  95. Hardman JG, Robison GA, Sutherland EW (1971) Cyclic nucleotides. Annu Rev Physiol 33:311–336CrossRefPubMedGoogle Scholar
  96. Heitzmann H (1972) Rhodopsin is the predominant protein of rod outer segment membranes. Nat New Biol 235:114CrossRefPubMedGoogle Scholar
  97. Hekman M, Feder D, Keenan AK, Gal A, Klein HW, Pfeuffer T, Levitzki A, Helmreich EJ (1984) Reconstitution of β-adrenergic receptor with components of adenylate cyclase. EMBO J 3:3339–3345CrossRefPubMedPubMedCentralGoogle Scholar
  98. Herrmann E, Gierschik P, Jakobs KH (1989) Neomycin induces high-affinity agonist binding of G-protein-coupled receptors. Eur J Biochem 185:677–683CrossRefPubMedGoogle Scholar
  99. Hildebrandt JD, Hanoune J, Birnbaumer L (1982) Guanine nucleotide inhibition of cyc S49 mouse lymphoma cell membrane adenylyl cyclase. J Biol Chem 257:14723–14725PubMedGoogle Scholar
  100. Hilf G, Gierschik P, Jakobs KH (1989) Muscarinic acetylcholine receptor-stimulated binding of guanosine 5′-O-(3-thiotriphosphate) to guanine-nucleotide-binding proteins in cardiac membranes. Eur J Biochem 186:725–731CrossRefPubMedGoogle Scholar
  101. Hilf G, Jakobs KH (1989) Activation of cardiac G-proteins by muscarinic acetylcholine receptors: regulation by Mg2+ and Na+ ions. Eur J Pharmacol 172:155–163CrossRefPubMedGoogle Scholar
  102. Hilf G, Jakobs KH (1992a) Activation of solubilized G-proteins by muscarinic acetylcholine receptors. Cell Signal 4:787–794CrossRefPubMedGoogle Scholar
  103. Hilf G, Jakobs KH (1992b) Agonist-independent inhibition of G protein activation by muscarinic acetylcholine receptor antagonists in cardiac membranes. Eur J Pharmacol 225:245–252CrossRefPubMedGoogle Scholar
  104. Hilf G, Kupprion C, Wieland T, Jakobs KH (1992) Dissociation of guanosine 5′-[γ-thio]triphosphate from guanine-nucleotide-binding regulatory proteins in native cardiac membranes. Regulation by nucleotides and muscarinic acetylcholine receptors. Eur J Biochem 204:725–731CrossRefPubMedGoogle Scholar
  105. Himmel HM, Meyer zu Heringdorf D, Graf E, Dobrev D, Kortner A, Schuler S, Jakobs KH, Ravens U (2000) Evidence for Edg-3 receptor-mediated activation of IK.ACh by sphingosine-1-phosphate in human atrial cardiomyocytes. Mol Pharmacol 58:449–454CrossRefPubMedGoogle Scholar
  106. Himmel HM, Meyer zu Heringdorf D, Windorfer B, van Koppen CJ, Ravens U, Jakobs KH (1998) Guanine nucleotide-sensitive inhibition of L-type Ca2+ current by lysosphingolipids in RINm5F insulinoma cells. Mol Pharmacol 53:862–869PubMedGoogle Scholar
  107. Hippe HJ, Abu-Taha I, Wolf NM, Katus HA, Wieland T (2011) Through scaffolding and catalytic actions nucleoside diphosphate kinase B differentially regulates basal and β-adrenoceptor-stimulated cAMP synthesis. Cell Signal 23:579–585CrossRefPubMedGoogle Scholar
  108. Hippe HJ, Luedde M, Lutz S, Koehler H, Eschenhagen T, Frey N, Katus HA, Wieland T, Niroomand F (2007) Regulation of cardiac cAMP synthesis and contractility by nucleoside diphosphate kinase B/G protein βγ dimer complexes. Circ Res 100:1191–1199CrossRefPubMedGoogle Scholar
  109. Hippe HJ, Lutz S, Cuello F, Knorr K, Vogt A, Jakobs KH, Wieland T, Niroomand F (2003) Activation of heterotrimeric G proteins by a high energy phosphate transfer via nucleoside diphosphate kinase (NDPK) B and Gβ subunits. Specific activation of Gsα by an NDPK B.Gβγ complex in H10 cells. J Biol Chem 278:7227–7233CrossRefPubMedGoogle Scholar
  110. Hippe HJ, Wolf NM, Abu-Taha I, Mehringer R, Just S, Lutz S, Niroomand F, Postel EH, Katus HA, Rottbauer W, Wieland T (2009) The interaction of nucleoside diphosphate kinase B with Gβγ dimers controls heterotrimeric G protein function. Proc Natl Acad Sci U S A 106:16269–16274CrossRefPubMedPubMedCentralGoogle Scholar
  111. Hommers LG, Klenk C, Dees C, Bünemann M (2010) G proteins in reverse mode: receptor-mediated GTP release inhibits G protein and effector function. J Biol Chem 285:8227–8233CrossRefPubMedPubMedCentralGoogle Scholar
  112. Hori T, Okuno T, Hirata K, Yamashita K, Kawano Y, Yamamoto M, Hato M, Nakamura M, Shimizu T, Yokomizo T, Miyano M, Yokoyama S (2018) Na+-mimicking ligands stabilize the inactive state of leukotriene B4 receptor BLT1. Nat Chem Biol 14:262–269CrossRefPubMedGoogle Scholar
  113. Huang C, Hepler JR, Gilman AG, Mumby SM (1997) Attenuation of Gi- and Gq-mediated signaling by expression of RGS4 or GAIP in mammalian cells. Proc Natl Acad Sci U S A 94:6159–6163CrossRefPubMedPubMedCentralGoogle Scholar
  114. Illenberger D, Schwald F, Pimmer D, Binder W, Maier G, Dietrich A, Gierschik P (1998) Stimulation of phospholipase C-β2 by the Rho GTPases Cdc42Hs and Rac1. EMBO J 17:6241–6249CrossRefPubMedPubMedCentralGoogle Scholar
  115. Iyengar R, Birnbaumer L (1982) Hormone receptor modulates the regulatory component of adenylyl cyclase by reducing its requirement for Mg2+ and enhancing its extent of activation by guanine nucleotides. Proc Natl Acad Sci U S A 79:5179–5183CrossRefPubMedPubMedCentralGoogle Scholar
  116. Jakobs KH, Aktories K, Schultz G (1979) GTP-dependent inhibition of cardiac adenylate cyclase by muscarinic cholinergic agonists. Naunyn Schmiedeberg's Arch Pharmacol 310:113–119CrossRefGoogle Scholar
  117. Jakobs KH, Aktories K, Schultz G (1981) Inhibition of adenylate cyclase by hormones and neurotransmitters. Adv Cyclic Nucleotide Res 14:173–187PubMedGoogle Scholar
  118. Jakobs KH, Aktories K, Schultz G (1983) A nucleotide regulatory site for somatostatin inhibition of adenylate cyclase in S49 lymphoma cells. Nature 303:177–178CrossRefPubMedGoogle Scholar
  119. Jakobs KH, Lasch P, Minuth M, Aktories K, Schultz G (1982) Uncoupling of alpha-adrenoceptor-mediated inhibition of human platelet adenylate cyclase by N-ethylmaleimide. J Biol Chem 257:2829–2833PubMedGoogle Scholar
  120. Jakobs KH, Saur W, Schultz G (1976) Reduction of adenylate cyclase activity in lysates of human platelets by the α-adrenergic component of epinephrine. J Cyclic Nucleotide Res 2:381–392PubMedGoogle Scholar
  121. Jakobs KH, Saur W, Schultz G (1978) Inhibition of platelet adenylate cyclase by epinephrine requires GTP. FEBS Lett 85:167–170CrossRefPubMedGoogle Scholar
  122. Jakobs KH, Schultz G (1970) Effects of various hormones and drugs on adenyl cyclase of rat kidney. Naunyn-Schmiedebergs Archiv für Pharmakologie 266:364–365CrossRefPubMedGoogle Scholar
  123. Jakobs KH, Schultz G (1980) Actions of hormones and neurotransmitters at the plasma membrane: inhibition of adenylate cyclase. Trends Pharmacol Sci 1:331–333CrossRefGoogle Scholar
  124. Jakobs KH, Schultz G (1983) Occurrence of a hormone-sensitive inhibitory coupling component of the adenylate cyclase in S49 lymphoma cyc variants. Proc Natl Acad Sci U S A 80:3899–3902CrossRefPubMedPubMedCentralGoogle Scholar
  125. Jakobs KH, Schultz K, Schultz G (1972) Inhibition of adenyl cyclase preparations from rat kidney by calcium ions and various diuretics. Naunyn Schmiedeberg's Arch Pharmacol 273:248–266CrossRefGoogle Scholar
  126. Jakobs KH, Wieland T (1989) Evidence for receptor-regulated phosphotransfer reactions involved in activation of the adenylate cyclase inhibitory G protein in human platelet membranes. Eur J Biochem 183:115–121CrossRefPubMedGoogle Scholar
  127. Janin J, Dumas C, Morera S, Xu Y, Meyer P, Chiadmi M, Cherfils J (2000) Three-dimensional structure of nucleoside diphosphate kinase. J Bioenerg Biomembr 32:215–225Google Scholar
  128. Jard S, Cantau B, Jakobs KH (1981) Angiotensin II and α-adrenergic agonists inhibit rat liver adenylate cyclase. J Biol Chem 256:2603–2606PubMedGoogle Scholar
  129. Johnson EN, Shi X, Cassaday J, Ferrer M, Strulovici B, Kunapuli P (2008) A 1,536-well [35S]GTPγS scintillation proximity binding assay for ultra-high-throughput screening of an orphan galphai-coupled GPCR. Assay Drug Dev Technol 6:327–337CrossRefPubMedGoogle Scholar
  130. Katada T, Gilman AG, Watanabe Y, Bauer S, Jakobs KH (1985) Protein kinase C phosphorylates the inhibitory guanine-nucleotide-binding regulatory component and apparently suppresses its function in hormonal inhibition of adenylate cyclase. Eur J Biochem 151:431–437CrossRefPubMedGoogle Scholar
  131. Katada T, Ui M (1982) ADP ribosylation of the specific membrane protein of C6 cells by islet-activating protein associated with modification of adenylate cyclase activity. J Biol Chem 257:7210–7216PubMedGoogle Scholar
  132. Kather H, Aktories K, Schulz G, Jakobs KH (1983) Islet-activating protein discriminates the antilipolytic mechanism of insulin from that of other antilipolytic compounds. FEBS Lett 161:149–152CrossRefPubMedGoogle Scholar
  133. Kather H, Bieger W, Michel G, Aktories K, Jakobs KH (1985) Human fat cell lipolysis is primarily regulated by inhibitory modulators acting through distinct mechanisms. J Clin Invest 76:1559–1565CrossRefPubMedPubMedCentralGoogle Scholar
  134. Katritch V, Cherezov V, Stevens RC (2013) Structure-function of the G protein-coupled receptor superfamily. Annu Rev Pharmacol Toxicol 53:531–556CrossRefGoogle Scholar
  135. Kawasaki H, Springett GM, Mochizuki N, Toki S, Nakaya M, Matsuda M, Housman DE, Graybiel AM (1998) A family of cAMP-binding proteins that directly activate Rap1. Science (New York, NY) 282:2275–2279CrossRefGoogle Scholar
  136. Keiper M, Stope MB, Szatkowski D, Bohm A, Tysack K, Vom Dorp F, Saur O, Oude Weernink PA, Evellin S, Jakobs KH, Schmidt M (2004) Epac- and Ca2+-controlled activation of Ras and extracellular signal-regulated kinases by Gs-coupled receptors. J Biol Chem 279:46497–46508CrossRefPubMedGoogle Scholar
  137. Kim M, MS A, Ewald AJ, Werb Z, Mostov KE (2015) p114RhoGEF governs cell motility and lumen formation during tubulogenesis through a ROCK-myosin-II pathway. J Cell Sci 128:4317–4327CrossRefPubMedPubMedCentralGoogle Scholar
  138. Kozasa T, Jiang X, Hart MJ, Sternweis PM, Singer WD, Gilman AG, Bollag G, Sternweis PC (1998) p115 RhoGEF, a GTPase activating protein for Gα12 and Gα13. Science (New York, NY) 280:2109–2111CrossRefGoogle Scholar
  139. Kühn B, Christel C, Wieland T, Schultz G, Gudermann T (2002) G-protein βγ-subunits contribute to the coupling specificity of the β2-adrenergic receptor to Gs. Naunyn Schmiedeberg's Arch Pharmacol 365:231–241CrossRefGoogle Scholar
  140. Kupper RW, Dewald B, Jakobs KH, Baggiolini M, Gierschik P (1992) G-protein activation by interleukin 8 and related cytokines in human neutrophil plasma membranes. The Biochemical Journal 282(Pt 2):429–434CrossRefPubMedPubMedCentralGoogle Scholar
  141. Kupprion C, Wieland T, Jakobs KH (1993) Receptor-stimulated dissociation of GTP[S] from Gi-proteins in membranes of HL-60 cells. Cell Signal 5:425–433CrossRefPubMedGoogle Scholar
  142. Kurose H, Katada T, Haga T, Haga K, Ichiyama A, Ui M (1986) Functional interaction of purified muscarinic receptors with purified inhibitory guanine nucleotide regulatory proteins reconstituted in phospholipid vesicles. J Biol Chem 261:6423–6428PubMedGoogle Scholar
  143. Kwok-Keung Fung B, Stryer L (1980) Photolyzed rhodopsin catalyzes the exchange of GTP for bound GDP in retinal rod outer segments. Proc Natl Acad Sci U S A 77:2500–2504CrossRefPubMedPubMedCentralGoogle Scholar
  144. Laudette M, Zuo H, Lezoualc'h F, Schmidt M (2018) Epac function and cAMP scaffolds in the heart and lung. J Cardiovas Dev Dis 5:E9CrossRefGoogle Scholar
  145. Lee MJ, Van Brocklyn JR, Thangada S, Liu CH, Hand AR, Menzeleev R, Spiegel S, Hla T (1998) Sphingosine-1-phosphate as a ligand for the G protein-coupled receptor EDG-1. Science (New York, NY) 279:1552–1555CrossRefGoogle Scholar
  146. Li X, Gao M, Han X, Tao S, Zheng D, Cheng Y, Yu R, Han G, Schmidt M, Han L (2012) Disruption of the phospholipase D gene attenuates the virulence of Aspergillus fumigatus. Infect Immun 80:429–440CrossRefPubMedPubMedCentralGoogle Scholar
  147. Lichte K, Rossi R, Danneberg K, ter Braak M, Kurschner U, Jakobs KH, Kleuser B, Meyer zu Heringdorf D (2008) Lysophospholipid receptor-mediated calcium signaling in human keratinocytes. J Invest Dermatol 128:1487–1498CrossRefPubMedGoogle Scholar
  148. Liebmann C, Nawrath S, Schnittler M, Schubert H, Jakobs KH (1992) Binding characteristics and functional G protein coupling of muscarinic acetylcholine receptors in rat duodenum smooth muscle membranes. Naunyn Schmiedeberg's Arch Pharmacol 345:7–15CrossRefGoogle Scholar
  149. Liebmann C, Schnittler M, Nawrath S, Jakobs KH (1991) High-affinity bradykinin receptor-catalyzed G protein activation in rat myometrium. Eur J Pharmacol 207:67–71CrossRefPubMedGoogle Scholar
  150. Lin CW, Miller TR, Witte DG, Bianchi BR, Stashko M, Manelli AM, Frail DE (1995) Characterization of cloned human dopamine D1 receptor-mediated calcium release in 293 cells. Mol Pharmacol 47:131–139PubMedGoogle Scholar
  151. Liscovitch M, Chalifa V, Pertile P, Chen CS, Cantley LC (1994) Novel function of phosphatidylinositol 4,5-bisphosphate as a cofactor for brain membrane phospholipase D. J Biol Chem 269:21403–21406PubMedGoogle Scholar
  152. Liu M, Simon MI (1996) Regulation by cAMP-dependent protein kinease of a G-protein-mediated phospholipase C. Nature 382:83–87CrossRefPubMedGoogle Scholar
  153. Liu W, Chun E, Thompson AA, Chubukov P, Xu F, Katritch V, Han GW, Roth CB, Heitman LH, IJ AP, Cherezov V, Stevens RC (2012) Structural basis for allosteric regulation of GPCRs by sodium ions. Science (New York, NY) 337:232–236CrossRefGoogle Scholar
  154. Lopez De Jesus M, Stope MB, Oude Weernink PA, Mahlke Y, Borgermann C, Ananaba VN, Rimmbach C, Rosskopf D, Michel MC, Jakobs KH, Schmidt M (2006) Cyclic AMP-dependent and Epac-mediated activation of R-Ras by G protein-coupled receptors leads to phospholipase D stimulation. J Biol Chem 281:21837–21847CrossRefPubMedGoogle Scholar
  155. Lopez I, Mak EC, Ding J, Hamm HE, Lomasney JW (2001) A novel bifunctional phospholipase c that is regulated by Gα12 and stimulates the Ras/mitogen-activated protein kinase pathway. J Biol Chem 276:2758–2765CrossRefPubMedGoogle Scholar
  156. Lutz S, Freichel-Blomquist A, Rümenapp U, Schmidt M, Jakobs KH, Wieland T (2004) p63RhoGEF and GEFT are Rho-specific guanine nucleotide exchange factors encoded by the same gene. Naunyn Schmiedeberg's Arch Pharmacol 369:540–546CrossRefGoogle Scholar
  157. Lutz S, Freichel-Blomquist A, Yang Y, Rümenapp U, Jakobs KH, Schmidt M, Wieland T (2005) The guanine nucleotide exchange factor p63RhoGEF, a specific link between Gq/11-coupled receptor signaling and RhoA. J Biol Chem 280:11134–11139CrossRefPubMedGoogle Scholar
  158. Lutz S, Mohl M, Rauch J, Weber P, Wieland T (2013) RhoGEF17, a rho-specific guanine nucleotide exchange factor activated by phosphorylation via cyclic GMP-dependent kinase Ialpha. Cell Signal 25:630–638CrossRefPubMedGoogle Scholar
  159. Lutz S, Mura R, Baltus D, Movsesian M, Kubler W, Niroomand F (2001) Increased activity of membrane-associated nucleoside diphosphate kinase and inhibition of cAMP synthesis in failing human myocardium. Cardiovasc Res 49:48–55CrossRefPubMedGoogle Scholar
  160. Lutz S, Shankaranarayanan A, Coco C, Ridilla M, Nance MR, Vettel C, Baltus D, Evelyn CR, Neubig RR, Wieland T, Tesmer JJ (2007) Structure of Gαq-p63RhoGEF-RhoA complex reveals a pathway for the activation of RhoA by GPCRs. Science (New York, NY) 318:1923–1927CrossRefGoogle Scholar
  161. Massink A, Gutierrez-de-Teran H, Lenselink EB, Ortiz Zacarias NV, Xia L, Heitman LH, Katritch V, Stevens RC, IJzerman AP (2015) Sodium ion binding pocket mutations and adenosine A2A receptor function. Mol Pharmacol 87:305–313CrossRefPubMedPubMedCentralGoogle Scholar
  162. Massink A, Louvel J, Adlere I, van Veen C, Huisman BJ, Dijksteel GS, Guo D, Lenselink EB, Buckley BJ, Matthews H, Ranson M, Kelso M, IJzerman AP (2016) 5′-Substituted amiloride derivatives as allosteric modulators binding in the sodium ion pocket of the adenosine A2A receptor. J Med Chem 59:4769–4777CrossRefPubMedGoogle Scholar
  163. Metrich M, Lucas A, Gastineau M, Samuel JL, Heymes C, Morel E, Lezoualc'h F (2008) Epac mediates β-adrenergic receptor-induced cardiomyocyte hypertrophy. Circ Res 102:959–965CrossRefPubMedGoogle Scholar
  164. Meyer zu Heringdorf D (2004) Lysophospholipid receptor-dependent and -independent calcium signaling. J Cell Biochem 92:937–948CrossRefPubMedGoogle Scholar
  165. Meyer zu Heringdorf D, Himmel HM, Jakobs KH (2002) Sphingosylphosphorylcholine-biological functions and mechanisms of action. Biochim Biophys Acta 1582:178–189CrossRefPubMedGoogle Scholar
  166. Meyer zu Heringdorf D, Ihlefeld K, Pfeilschifter J (2013) Pharmacology of the sphingosine-1-phosphate signalling system. Handb Exp Pharmacol 239–253Google Scholar
  167. Meyer zu Heringdorf D, Lass H, Alemany R, Laser KT, Neumann E, Zhang C, Schmidt M, Rauen U, Jakobs KH, van Koppen CJ (1998a) Sphingosine kinase-mediated Ca2+ signalling by G-protein-coupled receptors. EMBO J 17:2830–2837CrossRefPubMedPubMedCentralGoogle Scholar
  168. Meyer zu Heringdorf D, Lass H, Kuchar I, Lipinski M, Alemany R, Rümenapp U, Jakobs KH (2001) Stimulation of intracellular sphingosine-1-phosphate production by G-protein-coupled sphingosine-1-phosphate receptors. Eur J Pharmacol 414:145–154CrossRefPubMedGoogle Scholar
  169. Meyer zu Heringdorf D, Liliom K, Schaefer M, Danneberg K, Jaggar JH, Tigyi G, Jakobs KH (2003a) Photolysis of intracellular caged sphingosine-1-phosphate causes Ca2+ mobilization independently of G-protein-coupled receptors. FEBS Lett 554:443–449CrossRefPubMedGoogle Scholar
  170. Meyer zu Heringdorf D, Niederdraing N, Neumann E, Frode R, Lass H, Van Koppen CJ, Jakobs KH (1998b) Discrimination between plasma membrane and intracellular target sites of sphingosylphosphorylcholine. Eur J Pharmacol 354:113–122CrossRefPubMedGoogle Scholar
  171. Meyer zu Heringdorf D, van Koppen CJ, Windorfer B, Himmel HM, Jakobs KH (1996) Calcium signalling by G protein-coupled sphingolipid receptors in bovine aortic endothelial cells. Naunyn Schmiedeberg's Arch Pharmacol 354:397–403CrossRefGoogle Scholar
  172. Meyer zu Heringdorf D, Vincent ME, Lipinski M, Danneberg K, Stropp U, Wang DA, Tigyi G, Jakobs KH (2003b) Inhibition of Ca2+ signalling by the sphingosine 1-phosphate receptor S1P1. Cell Signal 15:677–687CrossRefGoogle Scholar
  173. Mitin N, Rossman KL, Currin R, Anne S, Marshall TW, Bear JE, Bautch VL, Der CJ (2013) The RhoGEF TEM4 regulates endothelial cell migration by suppressing actomyosin contractility. PLoS One 8:e66260CrossRefPubMedPubMedCentralGoogle Scholar
  174. Mitin N, Rossman KL, Der CJ (2012) Identification of a novel actin-binding domain within the Rho guanine nucleotide exchange factor TEM4. PLoS One 7:e41876CrossRefPubMedPubMedCentralGoogle Scholar
  175. Mizuki Y, Takaki M, Okahisa Y, Sakamoto S, Kodama M, Ujike H, Uchitomi Y (2014) Human Rho guanine nucleotide exchange factor 11 gene is associated with schizophrenia in a Japanese population. Human Psychopharmacol 29:552–558CrossRefGoogle Scholar
  176. Mizuki Y, Takaki M, Sakamoto S, Okamoto S, Kishimoto M, Okahisa Y, Itoh M, Yamada N (2016) Human Rho guanine nucleotide exchange factor 11 (ARHGEF11) regulates dendritic morphogenesis. Int J Mol Sci 18(1):67CrossRefPubMedCentralGoogle Scholar
  177. Morera S, Chiadmi M, LeBras G, Lascu I, Janin J (2002) Mechanism of phosphate transfer by nucleoside diphosphate kinase: X-ray structures of the phosphohistidine intermediate of the enzymes from Drosophila and Dictyostelium. Biochemistry 34(35):11062–11070Google Scholar
  178. Motulsky HJ, Insel PA (1983) ADP- and epinephrine-elicited release of [3H]guanylylimidodiphosphate from platelet membranes Implications Recep-Ni Stoichiometry. FEBS Lett 164:13–16CrossRefPubMedGoogle Scholar
  179. Munoz-Llancao P, de Gregorio C, Las Heras M, Meinohl C, Noorman K, Boddeke E, Cheng X, Lezoualc'h F, Schmidt M, Gonzalez-Billault C (2017) Microtubule-regulating proteins and cAMP-dependent signaling in neuroblastoma differentiation. Cytoskeleton (Hoboken, NJ) 74:143–158CrossRefGoogle Scholar
  180. Munoz-Llancao P, Henriquez DR, Wilson C, Bodaleo F, Boddeke EW, Lezoualc'h F, Schmidt M, Gonzalez-Billault C (2015) Exchange protein directly activated by cAMP (EPAC) regulates neuronal polarization through Rap1B. J Neurosci 35:11315–11329CrossRefPubMedGoogle Scholar
  181. Ngok SP, Geyer R, Kourtidis A, Mitin N, Feathers R, Der C, Anastasiadis PZ (2013) TEM4 is a junctional Rho GEF required for cell-cell adhesion, monolayer integrity and barrier function. J Cell Sci 126:3271–3277CrossRefPubMedPubMedCentralGoogle Scholar
  182. Niu J, Profirovic J, Pan H, Vaiskunaite R, Voyno-Yasenetskaya T (2003) G protein βγ subunits stimulate p114RhoGEF, a guanine nucleotide exchange factor for RhoA and Rac1: regulation of cell shape and reactive oxygen species production. Circ Res 93:848–856CrossRefPubMedGoogle Scholar
  183. Northup JK, Smigel MD, Sternweis PC, Gilman AG (1983a) The subunits of the stimulatory regulatory component of adenylate cyclase. Resolution of the activated 45,000-Dalton α subunit. J Biol Chem 258:11369–11376PubMedGoogle Scholar
  184. Northup JK, Sternweis PC, Gilman AG (1983b) The subunits of the stimulatory regulatory component of adenylate cyclase. Resolution, activity, and properties of the 35,000-Dalton β subunit. J Biol Chem 258:11361–11368PubMedGoogle Scholar
  185. 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 77:6516–6520CrossRefPubMedPubMedCentralGoogle Scholar
  186. Offermanns S, Wieland T, Homann D, Sandmann J, Bombien E, Spicher K, Schultz G, Jakobs KH (1994) Transfected muscarinic acetylcholine receptors selectively couple to Gi-type G proteins and Gq/11. Mol Pharmacol 45:890–898PubMedGoogle Scholar
  187. Oldenburger A, Roscioni SS, Jansen E, Menzen MH, Halayko AJ, Timens W, Meurs H, Maarsingh H, Schmidt M (2012) Anti-inflammatory role of the cAMP effectors Epac and PKA: implications in chronic obstructive pulmonary disease. PLoS One 7:e31574CrossRefPubMedPubMedCentralGoogle Scholar
  188. Oldenburger A, Timens W, Bos S, Smit M, Smrcka AV, Laurent AC, Cao J, Hylkema M, Meurs H, Maarsingh H, Lezoualc'h F, Schmidt M (2014) Epac1 and Epac2 are differentially involved in inflammatory and remodeling processes induced by cigarette smoke. FASEB J: Official Publication of the Federation of American Societies for Experimental Biology 28:4617–4628CrossRefGoogle Scholar
  189. Olivera A, Spiegel S (1993) Sphingosine-1-phosphate as second messenger in cell proliferation induced by PDGF and FCS mitogens. Nature 365:557–560CrossRefPubMedGoogle Scholar
  190. Ongherth A, Pasch S, Wuertz CM, Nowak K, Kittana N, Weis CA, Jatho A, Vettel C, Tiburcy M, Toischer K, Hasenfuss G, Zimmermann WH, Wieland T, Lutz S (2015) p63RhoGEF regulates auto- and paracrine signaling in cardiac fibroblasts. J Mol Cell Cardiol 88:39–54CrossRefPubMedGoogle Scholar
  191. Ostroveanu A, van der Zee EA, Eisel UL, Schmidt M, Nijholt IM (2010) Exchange protein activated by cyclic AMP 2 (Epac2) plays a specific and time-limited role in memory retrieval. Hippocampus 20:1018–1026CrossRefPubMedGoogle Scholar
  192. Oude Weernink PA, Han L, Jakobs KH, Schmidt M (2007) Dynamic phospholipid signaling by G protein-coupled receptors. Biochim Biophys Acta 1768:888–900CrossRefPubMedGoogle Scholar
  193. Oude Weernink PA, Schmidt M, Jakobs KH (2004) Regulation and cellular roles of phosphoinositide 5-kinases. Eur J Pharmacol 500:87–99CrossRefPubMedGoogle Scholar
  194. Oude Weernink PA, Schulte P, Guo Y, Wetzel J, Amano M, Kaibuchi K, Haverland S, Voss M, Schmidt M, Mayr GW, Jakobs KH (2000) Stimulation of phosphatidylinositol-4-phosphate 5-kinase by Rho-kinase. J Biol Chem 275:10168–10174CrossRefPubMedGoogle Scholar
  195. Park D, Jhon DY, Lee CW, Lee KH, Rhee SG (1993) Activation of phospholipase C isozymes by G protein βγ subunits. J Biol Chem 268:4573–4576PubMedGoogle Scholar
  196. Park DJ, Min HK, Rhee SG (1992) Inhibition of CD3-linked phospholipase C by phorbol ester and by cAMP is associated with decreased phosphotyrosine and increased phosphoserine contents of PLC-γ 1. J Biol Chem 267:1496–1501PubMedGoogle Scholar
  197. Parnell E, Palmer TM, Yarwood SJ (2015) The future of EPAC-targeted therapies: agonism versus antagonism. Trends Pharmacol Sci 36:203–214CrossRefPubMedPubMedCentralGoogle Scholar
  198. Pedersen SE, Ross EM (1982) Functional reconstitution of β-adrenergic receptors and the stimulatory GTP-binding protein of adenylate cyclase. Proc Natl Acad Sci U S A 79:7228–7232CrossRefPubMedPubMedCentralGoogle Scholar
  199. Proia RL, Hla T (2015) Emerging biology of sphingosine-1-phosphate: its role in pathogenesis and therapy. J Clin Invest 125:1379–1387CrossRefPubMedPubMedCentralGoogle Scholar
  200. Pugh EN, Lamb TD (2000) Phototransduction in vertrebrate rod and cones: molecular mechanisms of amplification, recovery, and light adaptation. In: G. SD, de Grip WJ, Pugh EN (eds.) Handbook of biological physics. pp. 183-255Google Scholar
  201. Rabiet MJ, Tardif M, Braun L, Boulay F (2002) Inhibitory effects of a dominant-interfering form of the Rho-GTPase Cdc42 in the chemoattractant-elicited signaling pathways leading to NADPH oxidase activation in differentiated HL-60 cells. Blood 100:1835–1844CrossRefPubMedGoogle Scholar
  202. Rasmussen SG, DeVree BT, Zou Y, Kruse AC, Chung KY, Kobilka TS, Thian FS, Chae PS, Pardon E, Calinski D, Mathiesen JM, Shah ST, Lyons JA, Caffrey M, Gellman SH, Steyaert J, Skiniotis G, Weis WI, Sunahara RK, Kobilka BK (2011) Crystal structure of the β2 adrenergic receptor-Gs protein complex. Nature 477:549–555CrossRefPubMedPubMedCentralGoogle Scholar
  203. Rich TC, Fagan KA, Tse TE, Schaack J, Cooper DM, Karpen JW (2001) A uniform extracellular stimulus triggers distinct cAMP signals in different compartments of a simple cell. Proc Natl Acad Sci U S A 98:13049–13054CrossRefPubMedPubMedCentralGoogle Scholar
  204. Robichaux WG 3rd, Cheng X (2018) Intracellular cAMP sensor EPAC: physiology, pathophysiology, and therapeutics development. Physiol Rev 98:919–1053CrossRefPubMedPubMedCentralGoogle Scholar
  205. Rümenapp U, Asmus M, Schablowski H, Woznicki M, Han L, Jakobs KH, Fahimi-Vahid M, Michalek C, Wieland T, Schmidt M (2001) The M3 muscarinic acetylcholine receptor expressed in HEK-293 cells signals to phospholipase D via G12 but not Gq-type G proteins: regulators of G proteins as tools to dissect pertussis toxin-resistant G proteins in receptor-effector coupling. J Biol Chem 276:2474–2479CrossRefPubMedGoogle Scholar
  206. Rümenapp U, Blomquist A, Schworer G, Schablowski H, Psoma A, Jakobs KH (1999) Rho-specific binding and guanine nucleotide exchange catalysis by KIAA0380, a dbl family member. FEBS Lett 459:313–318CrossRefPubMedGoogle Scholar
  207. Rümenapp U, Freichel-Blomquist A, Wittinghofer B, Jakobs KH, Wieland T (2002) A mammalian Rho-specific guanine-nucleotide exchange factor (p164-RhoGEF) without a pleckstrin homology domain. The Biochemical Journal 366:721–728CrossRefPubMedPubMedCentralGoogle Scholar
  208. Rümenapp U, Geiszt M, Wahn F, Schmidt M, Jakobs KH (1995) Evidence for ADP-ribosylation-factor-mediated activation of phospholipase D by M3 muscarinic acetylcholine receptor. Eur J Biochem 234:240–244CrossRefPubMedGoogle Scholar
  209. Rümenapp U, Lummen G, Virchow S, Hanske J, Meyer zu Heringdorf D, Jakobs KH (2000) Sphingolipid receptor signaling and function in human bladder carcinoma cells: inhibition of LPA- but enhancement of thrombin-stimulated cell motility. Naunyn Schmiedeberg's Arch Pharmacol 361:1–11CrossRefGoogle Scholar
  210. Rümenapp U, Schmidt M, Geiszt M, Jakobs KH (1996) Participation of small GTP-binding proteins in M3 muscarinic acetylcholine receptor signalling to phospholipase D and C. Prog Brain Res 109:209–216CrossRefPubMedGoogle Scholar
  211. Rümenapp U, Schmidt M, Olesch S, Ott S, Eichel-Streiber CV, Jakobs KH (1998) Tyrosine-phosphorylation-dependent and rho-protein-mediated control of cellular phosphatidylinositol 4,5-bisphosphate levels. The Biochemical Journal 334(Pt 3):625–631CrossRefPubMedPubMedCentralGoogle Scholar
  212. Rümenapp U, Schmidt M, Wahn F, Tapp E, Grannass A, Jakobs KH (1997) Characteristics of protein-kinase-C- and ADP-ribosylation-factor-stimulated phospholipase D activities in human embryonic kidney cells. Eur J Biochem 248:407–414CrossRefPubMedGoogle Scholar
  213. Sadana R, Dessauer CW (2009) Physiological roles for G protein-regulated adenylyl cyclase isoforms: insights from knockout and overexpression studies. Neuro-Signals 17:5–22CrossRefPubMedGoogle Scholar
  214. Salomon MR, Bourne HR (1981) Novel S49 lymphoma variants with aberrant cyclic AMP metabolism. Mol Pharmacol 19:109–116PubMedGoogle Scholar
  215. Sand C, Grandoch M, Borgermann C, Oude Weernink PA, Mahlke Y, Schwindenhammer B, Weber AA, Fischer JW, Jakobs KH, Schmidt M (2010) 8-pCPT-conjugated cyclic AMP analogs exert thromboxane receptor antagonistic properties. Thromb Haemost 103:662–678CrossRefPubMedGoogle Scholar
  216. Schmidt M, Huwe SM, Fasselt B, Homann D, Rümenapp U, Sandmann J, Jakobs KH (1994) Mechanisms of phospholipase D stimulation by M3 muscarinic acetylcholine receptors. Evidence for involvement of tyrosine phosphorylation. Eur J Biochem 225:667–675CrossRefPubMedGoogle Scholar
  217. Schmidt M, Bienek C, van Koppen CJ, Michel MC, Jakobs KH (1995a) Differential calcium signalling by M2 and M3 muscarinic acetylcholine receptors in a single cell type. Naunyn Schmiedeberg's Arch Pharmacol 352:469–476CrossRefGoogle Scholar
  218. Schmidt M, Fasselt B, Rümenapp U, Bienek C, Wieland T, van Koppen CJ, Jakobs KH (1995b) Rapid and persistent desensitization of M3 muscarinic acetylcholine receptor-stimulated phospholipase D. Concomitant sensitization of phospholipase C. J Biol Chem 270:19949–19956CrossRefPubMedGoogle Scholar
  219. Schmidt M, Bienek C, Rümenapp U, Zhang C, Lummen G, Jakobs KH, Just I, Aktories K, Moos M, von Eichel-Streiber C (1996a) A role for rho in receptor- and G protein-stimulated phospholipase C. Reduction in phosphatidylinositol 4,5-bisphosphate by Clostridium difficile toxin B. Naunyn Schmiedeberg's Arch Pharmacol 354:87–94CrossRefGoogle Scholar
  220. Schmidt M, Rümenapp U, Bienek C, Keller J, von Eichel-Streiber C, Jakobs KH (1996b) Inhibition of receptor signaling to phospholipase D by Clostridium difficile toxin B. Role of Rho proteins. J Biol Chem 271:2422–2426CrossRefPubMedGoogle Scholar
  221. Schmidt M, Rümenapp U, Nehls C, Ott S, Keller J, Von Eichel-Streiber C, Jakobs KH (1996c) Restoration of Clostridium difficile toxin-B-inhibited phospholipase D by phosphatidylinositol 4,5-bisphosphate. Eur J Biochem 240:707–712CrossRefPubMedGoogle Scholar
  222. Schmidt M, Voss M, Thiel M, Bauer B, Grannass A, Tapp E, Cool RH, de Gunzburg J, von Eichel-Streiber C, Jakobs KH (1998) Specific inhibition of phorbol ester-stimulated phospholipase D by Clostridium sordellii lethal toxin and Clostridium difficile toxin B-1470 in HEK-293 cells. Restoration by Ral GTPases. J Biol Chem 273:7413–7422CrossRefPubMedGoogle Scholar
  223. Schmidt M, Evellin S, Weernink PA, von Dorp F, Rehmann H, Lomasney JW, Jakobs KH (2001) A new phospholipase-C-calcium signalling pathway mediated by cyclic AMP and a Rap GTPase. Nat Cell Biol 3:1020–1024CrossRefPubMedGoogle Scholar
  224. Schmidt M, Oude Weernink PA, Vom Dorp F, Stope MB, Jakobs KH (2004) Mammalian phospholipase C. Adv Mol Cell Biol 33:433–453Google Scholar
  225. Schmidt M, Sand C, Jakobs KH, Michel MC, Weernink PA (2007) Epac and the cardiovascular system. Curr Opin Pharmacol 7:193–200CrossRefPubMedGoogle Scholar
  226. Schmidt M, Dekker FJ, Maarsingh H (2013) Exchange protein directly activated by cAMP (epac): a multidomain cAMP mediator in the regulation of diverse biological functions. Pharmacol Rev 65:670–709CrossRefPubMedGoogle Scholar
  227. Schwede F, Bertinetti D, Langerijs CN, Hadders MA, Wienk H, Ellenbroek JH, de Koning EJ, Bos JL, Herberg FW, Genieser HG, Janssen RA, Rehmann H (2015) Structure-guided design of selective Epac1 and Epac2 agonists. PLoS Biol 13:e1002038CrossRefPubMedPubMedCentralGoogle Scholar
  228. Seifert R, Rosenthal W, Schultz G, Wieland T, Gierschick P, Jakobs KH (1988) The role of nucleoside-diphosphate kinase reactions in G protein activation of NADPH oxidase by guanine and adenine nucleotides. Eur J Biochem 175:51–55CrossRefPubMedGoogle Scholar
  229. Siffert W, Rosskopf D, Moritz A, Wieland T, Kaldenberg-Stasch S, Kettler N, Hartung K, Beckmann S, Jakobs KH (1995) Enhanced G protein activation in immortalized lymphoblasts from patients with essential hypertension. J Clin Invest 96:759–766CrossRefPubMedPubMedCentralGoogle Scholar
  230. Sim-Selley LJ, Wilkerson JL, Burston JJ, Hauser KF, McLane V, Welch SP, Lichtman AH, Selley DE (2018) Differential tolerance to FTY720-induced antinociception in acute thermal and nerve injury mouse pain models: role of S1P receptor adaptation. J Pharmacol Exp Ther 366:509–518CrossRefPubMedGoogle Scholar
  231. Sim LJ, Selley DE, Childers SR (1995) In vitro autoradiography of receptor-activated G proteins in rat brain by agonist-stimulated guanylyl 5′-[γ-[35S]thio]-triphosphate binding. Proc Natl Acad Sci U S A 92:7242–7246CrossRefPubMedPubMedCentralGoogle Scholar
  232. Smrcka AV, Brown JH, Holz GG (2012) Role of phospholipase Cε in physiological phosphoinositide signaling networks. Cell Signal 24:1333–1343CrossRefPubMedPubMedCentralGoogle Scholar
  233. Smrcka AV, Sternweis PC (1993) Regulation of purified subtypes of phosphatidylinositol-specific phospholipase C β by G protein α and βγ subunits. J Biol Chem 268:9667–9674PubMedGoogle Scholar
  234. Snyder JT, Singer AU, Wing MR, Harden TK, Sondek J (2003) The pleckstrin homology domain of phospholipase C-β2 as an effector site for Rac. J Biol Chem 278:21099–21104CrossRefPubMedGoogle Scholar
  235. Song C, Gao Y, Tian Y, Han X, Chen Y, Tian DL (2013) Expression of p114RhoGEF predicts lymph node metastasis and poor survival of squamous-cell lung carcinoma patients. Tumour Biol: the Journal of the International Society for Oncodevelopmental Biology and Medicine 34:1925–1933CrossRefGoogle Scholar
  236. Song C, Hu CD, Masago M, Kariyai K, Yamawaki-Kataoka Y, Shibatohge M, Wu D, Satoh T, Kataoka T (2001) Regulation of a novel human phospholipase C, PLCε, through membrane targeting by Ras. J Biol Chem 276:2752–2757CrossRefPubMedGoogle Scholar
  237. Sternweis PC, Robishaw JD (1984) Isolation of two proteins with high affinity for guanine nucleotides from membranes of bovine brain. J Biol Chem 259:13806–13813PubMedGoogle Scholar
  238. Stope MB, Vom Dorp F, Szatkowski D, Bohm A, Keiper M, Nolte J, Oude Weernink PA, Rosskopf D, Evellin S, Jakobs KH, Schmidt M (2004) Rap2B-dependent stimulation of phospholipase C-ε by epidermal growth factor receptor mediated by c-Src phosphorylation of RasGRP3. Mol Cell Biol 24:4664–4676CrossRefPubMedPubMedCentralGoogle Scholar
  239. Strub GM, Maceyka M, Hait NC, Milstien S, Spiegel S (2010) Extracellular and intracellular actions of sphingosine-1-phosphate. Adv Exp Med Biol 688:141–155CrossRefPubMedPubMedCentralGoogle Scholar
  240. Sun Z, Smrcka AV, Chen S (2013) WDR26 functions as a scaffolding protein to promote Gβγ-mediated phospholipase C β2 (PLCβ2) activation in leukocytes. J Biol Chem 288:16715–16725CrossRefPubMedPubMedCentralGoogle Scholar
  241. Tanguy E, Kassas N, Vitale N (2018) Protein-phospholipd interaction motifs: a focus on phosphatidic acid. Biomolecules 8:20Google Scholar
  242. Tepper AD, Dammann H, Bominaar AA, Veron M (1994) Investigation of the active site and the conformational stability of nucleoside diphosphate kinase by site-directed mutagenesis. J Biol Chem 269:32175–32180Google Scholar
  243. ter Braak M, Danneberg K, Lichte K, Liphardt K, Ktistakis NT, Pitson SM, Hla T, Jakobs KH, Meyer zu Heringdorf D (2009) Gαq-mediated plasma membrane translocation of sphingosine kinase-1 and cross-activation of S1P receptors. Biochim Biophys Acta 1791:357–370CrossRefPubMedGoogle Scholar
  244. Terry SJ, Elbediwy A, Zihni C, Harris AR, Bailly M, Charras GT, Balda MS, Matter K (2012) Stimulation of cortical myosin phosphorylation by p114RhoGEF drives cell migration and tumor cell invasion. PLoS One 7:e50188CrossRefPubMedPubMedCentralGoogle Scholar
  245. Terry SJ, Zihni C, Elbediwy A, Vitiello E, Leefa Chong San IV, Balda MS, Matter K (2011) Spatially restricted activation of RhoA signalling at epithelial junctions by p114RhoGEF drives junction formation and morphogenesis. Nat Cell Biol 13:159–166CrossRefPubMedPubMedCentralGoogle Scholar
  246. Thal DM, Glukhova A, Sexton PM, Christopoulos A (2018) Structural insights into G-protein-coupled receptor allostery. Nature 559:45–53CrossRefPubMedGoogle Scholar
  247. Tolkovsky AM, Levitzki A (1978) Mode of coupling between the β-adrenergic receptor and adenylate cyclase in turkey erythrocytes. Biochemistry 17:3795CrossRefPubMedGoogle Scholar
  248. Toro MJ, Montoya E, Birnbaumer L (1987) Inhibitory regulation of adenylyl cyclases. Evidence inconsistent with βγ-complexes of Gi proteins mediating hormonal effects by interfering with activation of Gs. Mol Endocrinol (Baltimore, MD) 1:669–676CrossRefGoogle Scholar
  249. Toth AD, Schell R, Levay M, Vettel C, Theis P, Haslinger C, Alban F, Werhahn S, Frischbier L, Krebs-Haupenthal J, Thomas D, Grone HJ, Avkiran M, Katus HA, Wieland T, Backs J (2018) Inflammation leads through PGE/EP3 signaling to HDAC5/MEF2-dependent transcription in cardiac myocytes. EMBO Molecular Medicine 10:e8536CrossRefPubMedPubMedCentralGoogle Scholar
  250. Van Koppen CJ, Meyer zu Heringdorf M, Laser KT, Zhang C, Jakobs KH, Bünemann M, Pott L (1996a) Activation of a high affinity Gi protein-coupled plasma membrane receptor by sphingosine-1-phosphate. J Biol Chem 271:2082–2087CrossRefPubMedGoogle Scholar
  251. Van Koppen CJ, Meyer zu Heringdorf D, Zhang C, Laser KT, Jakobs KH (1996b) A distinct Gi protein-coupled receptor for sphingosylphosphorylcholine in human leukemia HL-60 cells and human neutrophils. Mol Pharmacol 49:956–961PubMedGoogle Scholar
  252. Ventimiglia MS, Rodriguez MR, Elverdin JC, Davio CA, Vatta MS, Bianciotti LG (2008) Atrial natriuretic factor intracellular signaling in the rat submandibular gland. Regul Pept 150:43–49CrossRefPubMedGoogle Scholar
  253. vom Dorp F, Sari AY, Sanders H, Keiper M, Oude Weernink PA, Jakobs KH, Schmidt M (2004) Inhibition of phospholipase C-ε by Gi-coupled receptors. Cell Signal 16:921–928Google Scholar
  254. Voss M, Weernink PA, Haupenthal S, Moller U, Cool RH, Bauer B, Camonis JH, Jakobs KH, Schmidt M (1999) Phospholipase D stimulation by receptor tyrosine kinases mediated by protein kinase C and a Ras/Ral signaling cascade. J Biol Chem 274:34691–34698CrossRefPubMedGoogle Scholar
  255. Wang H, Oestreich EA, Maekawa N, Bullard TA, Vikstrom KL, Dirksen RT, Kelley GG, Blaxall BC, Smrcka AV (2005) Phospholipase C ε modulates β-adrenergic receptor-dependent cardiac contraction and inhibits cardiac hypertrophy. Circ Res 97:1305–1313CrossRefPubMedGoogle Scholar
  256. Wescott MP, Kufareva I, Paes C, Goodman JR, Thaker Y, Puffer BA, Berdougo E, Rucker JB, Handel TM, Doranz BJ (2016) Signal transmission through the CXC chemokine receptor 4 (CXCR4) transmembrane helices. Proc Natl Acad Sci U S A 113:9928–9933CrossRefPubMedPubMedCentralGoogle Scholar
  257. Wettschureck N, Offermanns S (2005) Mammalian G proteins and their cell type specific functions. Physiol Rev 85:1159–1204CrossRefPubMedGoogle Scholar
  258. White KL, Eddy MT, Gao ZG, Han GW, Lian T, Deary A, Patel N, Jacobson KA, Katritch V, Stevens RC (2018) Structural connection between activation microswitch and allosteric sodium site in GPCR signaling. Structure (London, England: 1993) 26:259–269 e255CrossRefGoogle Scholar
  259. Wieland C, Jakobs KH, Wieland T (1994) Altered guanine nucleoside triphosphate binding to transducin by cholera toxin-catalysed ADP-ribosylation. Cell Signal 6:487–492CrossRefPubMedGoogle Scholar
  260. Wieland T, Bremerich J, Gierschik P, Jakobs KH (1991a) Contribution of nucleoside diphosphokinase to guanine nucleotide regulation of agonist binding to formyl peptide receptors. Eur J Pharmacol 208:17–23CrossRefPubMedGoogle Scholar
  261. Wieland T, Chen CK (1999) Regulators of G-protein signalling: a novel protein family involved in timely deactivation and desensitization of signalling via heterotrimeric G proteins. Naunyn Schmiedeberg's Arch Pharmacol 360:14–26CrossRefGoogle Scholar
  262. Wieland T, Gierschik P, Jakobs KH (1992a) G protein-mediated receptor-receptor interaction: studies with chemotactic receptors in membranes of human leukemia (HL 60) cells. Naunyn Schmiedeberg's Arch Pharmacol 346:475–481CrossRefGoogle Scholar
  263. Wieland T, Jakobs KH (1989) Receptor-regulated formation of GTP[γS] with subsequent persistent Gs-protein activation in membranes of human platelets. FEBS Lett 245:189–193CrossRefPubMedGoogle Scholar
  264. Wieland T, Jakobs KH (1992) Evidence for nucleoside diphosphokinase-dependent channeling of guanosine 5′-(γ-thio)triphosphate to guanine nucleotide-binding proteins. Mol Pharmacol 42:731–735PubMedGoogle Scholar
  265. Wieland T, Jakobs KH (1994) Measurement of receptor-stimulated guanosine 5'-O-(γ-thio)triphosphate binding by G proteins. Methods Enzymol 237:3–13CrossRefGoogle Scholar
  266. Wieland T, Kreiss J, Gierschik P, Jakobs KH (1992b) Role of GDP in formyl-peptide-receptor-induced activation of guanine-nucleotide-binding proteins in membranes of HL 60 cells. Eur J Biochem 205:1201–1206CrossRefPubMedGoogle Scholar
  267. Wieland T, Liedel K, Kaldenberg-Stasch S, Meyer zu Heringdorf D, Schmidt M, Jakobs KH (1995) Analysis of receptor-G protein interactions in permeabilized cells. Naunyn Schmiedeberg's Arch Pharmacol 351:329–336CrossRefGoogle Scholar
  268. Wieland T, Mittmann C (2003) Regulators of G-protein signalling: multifunctional proteins with impact on signalling in the cardiovascular system. Pharmacol Ther 97:95–115CrossRefPubMedGoogle Scholar
  269. Wieland T, Nürnberg B, Ulibarri I, Kaldenberg-Stasch S, Schultz G, Jakobs KH (1993) Guanine nucleotide-specific phosphate transfer by guanine nucleotide-binding regulatory protein β-subunits. Characterization of the phosphorylated amino acid. J Biol Chem 268:18111–18118Google Scholar
  270. Wieland T, Ronzani M, Jakobs KH (1992c) Stimulation and inhibition of human platelet adenylylcyclase by thiophosphorylated transducin βγ-subunits. J Biol Chem 267:20791–20797PubMedGoogle Scholar
  271. Wieland T, Ulibarri I, Gierschik P, Jakobs KH (1991b) Activation of signal-transducing guanine-nucleotide-binding regulatory proteins by guanosine 5′-[γ-thio]triphosphate. Information transfer by intermediately thiophosphorylated beta gamma subunits. Eur J Biochem 196:707–716CrossRefPubMedGoogle Scholar
  272. Williamson JR (1986) Role of inositol lipid breakdown in the generation of intracellular signals. State of the art lecture. Hypertension (Dallas, Tex: 1979) 8:Ii140–Ii156Google Scholar
  273. Wuster M, Costa T, Aktories K, Jakobs KH (1984) Sodium regulation of opioid agonist binding is potentiated by pertussis toxin. Biochem Biophys Res Commun 123:1107–1115CrossRefPubMedGoogle Scholar
  274. Xie Z, Ho WT, Spellman R, Cai S, Exton JH (2002) Mechanisms of regulation of phospholipase D1 and D2 by the heterotrimeric G proteins G13 and Gq. J Biol Chem 277:11979–11986CrossRefPubMedGoogle Scholar
  275. Xu X, Jin T (2017) ELMO proteins transduce G protein-coupled receptor signal to control reorganization of actin cytoskeleton in chemotaxis of eukaryotic cells. Small GTPases 22:1–9CrossRefGoogle Scholar
  276. Yang X, Li J, Fang Y, Zhang Z, Jin D, Chen X, Zhao Y, Li M, Huan L, Kent TA, Dong JF, Jiang R, Yang S, Jin L, Zhang J, Zhong TP, Yu F (2018) Rho guanine nucleotide exchange factor ARHGEF17 is a risk gene for intracranial aneurysms. Circ Genomic Precis Med 11:e002099CrossRefGoogle Scholar
  277. Zaccolo M, Magalhaes P, Pozzan T (2002) Compartmentalisation of cAMP and Ca2+ signals. Curr Opin Cell Biol 14:160–166CrossRefPubMedGoogle Scholar
  278. Zhou XB, Lutz S, Steffens F, Korth M, Wieland T (2007) Oxytocin receptors differentially signal via Gq and Gi proteins in pregnant and nonpregnant rat uterine myocytes: implications for myometrial contractility. Mol Endocrinol (Baltimore, MD) 21:740–752CrossRefGoogle Scholar
  279. Zhou XB, Wulfsen I, Lutz S, Utku E, Sausbier U, Ruth P, Wieland T, Korth M (2008) M2 muscarinic receptors induce airway smooth muscle activation via a dual, Gβγ-mediated inhibition of large conductance Ca2+-activated K+ channel activity. J Biol Chem 283:21036–21044CrossRefPubMedPubMedCentralGoogle Scholar
  280. Zondag GC, Postma FR, Etten IV, Verlaan I, Moolenaar WH (1998) Sphingosine 1-phosphate signalling through the G-protein-coupled receptor Edg-1. The Biochem J 330(Pt 2):605–609CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Institute for Experimental and Clinical Pharmacology and Toxicology, Faculty of MedicineAlbert Ludwigs UniversityFreiburgGermany
  2. 2.Institute of Pharmacology and ToxicologyUlm University Medical CenterUlmGermany
  3. 3.Institute of General Pharmacology and Toxicology, University Hospital Frankfurt am MainGoethe UniversityFrankfurt am MainGermany
  4. 4.Department of Molecular PharmacologyUniversity of GroningenGroningenThe Netherlands
  5. 5.Department of PharmacologyCharité University Medical Center Berlin, Campus Benjamin FranklinBerlinGermany
  6. 6.Experimental Pharmacology Mannheim (EPM), European Center for Angioscience (ECAS), Medical Faculty MannheimHeidelberg UniversityMannheimGermany

Personalised recommendations