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

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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.

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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

References

  • 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 135:881–897

    Article  CAS  PubMed  Google Scholar 

  • Aktories K (2011) Bacterial protein toxins that modify host regulatory GTPases. Nat Rev Microbiol 9:487–498

    Article  CAS  PubMed  Google Scholar 

  • Aktories K, Jakobs KH (1981) Epinephrine inhibits adenylate cyclase and stimulates a GTPase in human platelet membranes via alpha-adrenoceptors. FEBS Lett 130:235–238

    Article  CAS  PubMed  Google Scholar 

  • Aktories K, Jakobs KH (1984) Ni-Mediated inhibition of human platelet adenylate cyclase by thrombin. Eur J Biochem 145:333–338

    Article  CAS  PubMed  Google Scholar 

  • Aktories K, Jakobs KH, Schultz G (1980a) Nicotinic acid inhibits adipocyte adenylate cyclase in a hormone-like manner. FEBS Lett 115:11–14

    Article  CAS  PubMed  Google Scholar 

  • 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 107:100–104

    Article  CAS  PubMed  Google Scholar 

  • 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 312:167–173

    Article  CAS  Google Scholar 

  • 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 146:65–68

    Article  CAS  PubMed  Google Scholar 

  • Aktories K, Schultz G, Jakobs KH (1982b) Stimulation of a low Km GTPase by inhibitors of adipocyte adenylate cyclase. Mol Pharmacol 21:336–342

    CAS  PubMed  Google Scholar 

  • 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 158:169–173

    Article  CAS  PubMed  Google Scholar 

  • 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 156:88–92

    Article  CAS  PubMed  Google Scholar 

  • 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 509:239–244

    Article  CAS  PubMed  Google Scholar 

  • 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 274:3994–3999

    Article  CAS  PubMed  Google Scholar 

  • 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 58:491–497

    Article  CAS  PubMed  Google Scholar 

  • 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 23:5460–5467

    Article  CAS  PubMed  Google Scholar 

  • Attwood PV, Wieland T (2015) Nucleoside diphosphate kinase as protein histidine kinase. Naunyn Schmiedeberg's Arch Pharmacol 388:153–160

    Article  CAS  Google Scholar 

  • 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 23:44–54

    Article  CAS  PubMed  Google Scholar 

  • Bamburg JR (1999) Proteins of the ADF/cofilin family: essential regulators of actin dynamics. Annu Rev Cell Dev Biol 15:185–230

    Article  CAS  PubMed  Google Scholar 

  • Bamburg JR (2011) Listeria monocytogenes cell invasion: a new role for cofilin in co-ordinating actin dynamics and membrane lipids. Mol Microbiol 81:851–854

    Article  CAS  PubMed  Google Scholar 

  • 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 104:108–120

    Article  PubMed  PubMed Central  Google Scholar 

  • Beavo JA, Brunton LL (2002) Cyclic nucleotide research—still expanding after half a century. Nat Rev Mol Cell Biol 3:710–718

    Article  CAS  PubMed  Google Scholar 

  • Bernstein BW, Bamburg JR (2010) ADF/cofilin: a functional node in cell biology. Trends Cell Biol 20:187–195

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Birnbaumer L, Brown AM (1987) G protein opening of K+ channels. Nature 327:21–22

    Article  CAS  PubMed  Google Scholar 

  • 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 130:1871–1877

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 130:1878–1883

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bischoff A, Meyer zu Heringdorf D, Jakobs KH, Michel MC (2001) Lysosphingolipid receptor-mediated diuresis and natriuresis in anaesthetized rats. Br J Pharmacol 132:1925–1933

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Blaho VA, Hla T (2014) An update on the biology of sphingosine 1-phosphate receptors. J Lipid Res 55:1596–1608

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Blank JL, Brattain KA, Exton JH (1992) Activation of cytosolic phosphoinositide phospholipase C by G-protein βγ subunits. J Biol Chem 267:23069–23075

    CAS  PubMed  Google Scholar 

  • Blankenbach KV, Schwalm S, Pfeilschifter J, Meyer zu Heringdorf D (2016) Sphingosine-1-phosphate receptor-2 antagonists: therapeutic potential and potential risks. Front Pharmacol 7:167

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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):319–325

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 259:3560–3567

    CAS  PubMed  Google Scholar 

  • Bond RA, Ijzerman AP (2006) Recent developments in constitutive receptor activity and inverse agonism, and their potential for GPCR drug discovery. Trends Pharmacol Sci 27:92–96

    Article  CAS  PubMed  Google Scholar 

  • Boyer JL, Waldo GL, Harden TK (1992) βγ-Subunit activation of G-protein-regulated phospholipase C. J Biol Chem 267:25451–25456

    CAS  PubMed  Google Scholar 

  • 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–R19

    CAS  Google Scholar 

  • 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 9:883–897

    Article  CAS  PubMed  Google Scholar 

  • Brown HA, Thomas PG, Lindsley CW (2017) Targeting phospholipase D in cancer, infection and neurodegenerative disorders. Nat Rev Drug Discov 16:351–367

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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):701–707

    Article  PubMed  PubMed Central  Google Scholar 

  • Bunney TD, Katan M (2006) Phospholipase C ε: linking second messengers and small GTPases. Trends Cell Biol 16:640–648

    Article  CAS  PubMed  Google Scholar 

  • Bustelo XR (2014) Vav family exchange factors: an integrated regulatory and functional view. Small GTPases 5:9

    Article  PubMed  Google Scholar 

  • 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 32:331–338

    Article  CAS  PubMed  Google Scholar 

  • 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 8:16

    Google Scholar 

  • 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 360:684–686

    Article  CAS  PubMed  Google Scholar 

  • 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 206:821–831

    Article  CAS  PubMed  Google Scholar 

  • 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 24:1261–1269

    Article  CAS  PubMed  Google Scholar 

  • Cassel D, Selinger Z (1976) Catecholamine-stimulated GTPase activity in turkey erythrocyte membranes. Biochim Biophys Acta 452:538–551

    Article  CAS  PubMed  Google Scholar 

  • Cassel D, Selinger Z (1977a) Catecholamine-induced release of [3H]-Gpp(NH)p from turkey erythrocyte adenylate cyclase. J Cyclic Nucleotide Res 3:11–22

    CAS  PubMed  Google Scholar 

  • 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 74:3307–3311

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 321:12–23

    Article  CAS  PubMed  Google Scholar 

  • 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 540:133–144

    Article  CAS  PubMed  Google Scholar 

  • Chan H, Pitson SM (2013) Post-translational regulation of sphingosine kinases. Biochim Biophys Acta 1831:147–156

    Article  CAS  PubMed  Google Scholar 

  • 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:e06011

    Article  PubMed  PubMed Central  Google Scholar 

  • Chen H, Bernstein BW, Bamburg JR (2000) Regulating actin-filament dynamics in vivo. Trends Biochem Sci 25:19–23

    Article  CAS  PubMed  Google Scholar 

  • Chu J, Zheng H, Zhang YH, Loh HH, Law PY (2010) Agonist-dependent μ-opioid receptor signaling can lead to heterologous desensitization. Cell Signal 22:684–696

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 257:13257–13262

    CAS  PubMed  Google Scholar 

  • 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 22:476–483

    Article  CAS  PubMed  Google Scholar 

  • Cockcroft S (2001) Signalling roles of mammalian phospholipase D1 and D2. Cell Mol Life Sci: CMLS 58:1674–1687

    Article  CAS  PubMed  Google Scholar 

  • 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 86:7321–7325

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 37:383–394

    CAS  PubMed  Google Scholar 

  • 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 278:7220–7226

    Article  CAS  PubMed  Google Scholar 

  • 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 270:3554–3559

    Article  PubMed  Google Scholar 

  • 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 396:474–477

    Article  CAS  PubMed  Google Scholar 

  • 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 25:2478–2484

    Article  CAS  PubMed  Google Scholar 

  • Dhanasekaran N, Dermott JM (1996) Signaling by the G12 class of G proteins. Cell Signal 8:235–245

    Article  CAS  PubMed  Google Scholar 

  • 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 8:1208

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dusaban SS, Brown JH (2015) PLCε mediated sustained signaling pathways. Adv Biol Regul 57:17–23

    Article  CAS  PubMed  Google Scholar 

  • 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 277:16805–16813

    Article  CAS  PubMed  Google Scholar 

  • Exton JH (2002) Phospholipase D-structure, regulation and function. Rev Physiol Biochem Pharmacol 144:1–94

    Article  CAS  PubMed  Google Scholar 

  • 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 34:441–453

    Article  CAS  PubMed  Google Scholar 

  • 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 120:645–657

    Article  CAS  PubMed  Google Scholar 

  • Frohman MA (2015) The phospholipase D superfamily as therapeutic targets. Trends Pharmacol Sci 36:137–144

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 207:259–263

    Article  CAS  PubMed  Google Scholar 

  • 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 68:79–83

    Article  CAS  PubMed  Google Scholar 

  • 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 Chem

  • Ghosh TK, Bian J, Gill DL (1994) Sphingosine 1-phosphate generated in the endoplasmic reticulum membrane activates release of stored calcium. J Biol Chem 269:22628–22635

    CAS  PubMed  Google Scholar 

  • Gierschik P (1992) ADP-ribosylation of signal-transducing guanine nucleotide-binding proteins by pertussis toxin. Curr Top Microbiol Immunol 175:69–96

    CAS  PubMed  Google Scholar 

  • Gierschik P, Bouillon T, Jakobs KH (1994) Receptor-stimulated hydrolysis of guanosine 5′-triphosphate in membrane preparations. Methods Enzymol 237:13–26

    Article  CAS  PubMed  Google Scholar 

  • 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 261:8058–8062

    CAS  PubMed  Google Scholar 

  • Gierschik P, Jakobs KH (1987) Receptor-mediated ADP-ribosylation of a phospholipase C-stimulating G protein. FEBS Lett 224:219–223

    Article  CAS  PubMed  Google Scholar 

  • Gierschik P, McLeish K, Jakobs KH (1988) Regulation of G-protein-mediated signal transfer by ions. J Cardiovasc Pharmacol 12(Suppl 5):S20–S24

    Article  CAS  PubMed  Google Scholar 

  • 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 197:725–732

    Article  CAS  PubMed  Google Scholar 

  • 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 264:21470–21473

    CAS  PubMed  Google Scholar 

  • 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 172:481–492

    Article  CAS  PubMed  Google Scholar 

  • 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 183:97–105

    Article  CAS  PubMed  Google Scholar 

  • 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 266:8784–8789

  • 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 365:468–476

    Article  CAS  Google Scholar 

  • Grandoch M, Bujok V, Fleckenstein D, Schmidt M, Fischer JW, Weber AA (2009a) Epac inhibits apoptosis of human leukocytes. J Leukoc Biol 86:847–849

    Article  CAS  PubMed  Google Scholar 

  • 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 159:265–284

    Article  CAS  PubMed  Google Scholar 

  • 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 101:2038–2042

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grandt R, Aktories K, Jakobs KH (1986) Evidence for two GTPases activated by thrombin in membranes of human platelets. Biochem J 237:669–674

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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–S265

    CAS  Google Scholar 

  • Halls ML, Cooper DMF (2017) Adenylyl cyclase signalling complexes—pharmacological challenges and opportunities. Pharmacol Ther 172:171–180

    Article  CAS  PubMed  Google Scholar 

  • 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 26:4189–4202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 81:860–880

    Article  CAS  PubMed  Google Scholar 

  • 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:e21468

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hardman JG, Robison GA, Sutherland EW (1971) Cyclic nucleotides. Annu Rev Physiol 33:311–336

    Article  CAS  PubMed  Google Scholar 

  • Heitzmann H (1972) Rhodopsin is the predominant protein of rod outer segment membranes. Nat New Biol 235:114

    Article  CAS  PubMed  Google Scholar 

  • 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 3:3339–3345

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Herrmann E, Gierschik P, Jakobs KH (1989) Neomycin induces high-affinity agonist binding of G-protein-coupled receptors. Eur J Biochem 185:677–683

    Article  CAS  PubMed  Google Scholar 

  • Hildebrandt JD, Hanoune J, Birnbaumer L (1982) Guanine nucleotide inhibition of cyc− S49 mouse lymphoma cell membrane adenylyl cyclase. J Biol Chem 257:14723–14725

    CAS  PubMed  Google Scholar 

  • 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 186:725–731

    Article  CAS  PubMed  Google Scholar 

  • Hilf G, Jakobs KH (1989) Activation of cardiac G-proteins by muscarinic acetylcholine receptors: regulation by Mg2+ and Na+ ions. Eur J Pharmacol 172:155–163

    Article  CAS  PubMed  Google Scholar 

  • Hilf G, Jakobs KH (1992a) Activation of solubilized G-proteins by muscarinic acetylcholine receptors. Cell Signal 4:787–794

    Article  CAS  PubMed  Google Scholar 

  • Hilf G, Jakobs KH (1992b) Agonist-independent inhibition of G protein activation by muscarinic acetylcholine receptor antagonists in cardiac membranes. Eur J Pharmacol 225:245–252

    Article  CAS  PubMed  Google Scholar 

  • 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 204:725–731

    Article  CAS  PubMed  Google Scholar 

  • 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 58:449–454

    Article  CAS  PubMed  Google Scholar 

  • 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 53:862–869

    CAS  PubMed  Google Scholar 

  • 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 23:579–585

    Article  CAS  PubMed  Google Scholar 

  • 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 100:1191–1199

    Article  CAS  PubMed  Google Scholar 

  • 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 278:7227–7233

    Article  CAS  PubMed  Google Scholar 

  • 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 106:16269–16274

    Article  PubMed  PubMed Central  Google Scholar 

  • 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 285:8227–8233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 14:262–269

    Article  CAS  PubMed  Google Scholar 

  • 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 94:6159–6163

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 17:6241–6249

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 79:5179–5183

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jakobs KH, Aktories K, Schultz G (1979) GTP-dependent inhibition of cardiac adenylate cyclase by muscarinic cholinergic agonists. Naunyn Schmiedeberg's Arch Pharmacol 310:113–119

    Article  CAS  Google Scholar 

  • Jakobs KH, Aktories K, Schultz G (1981) Inhibition of adenylate cyclase by hormones and neurotransmitters. Adv Cyclic Nucleotide Res 14:173–187

    CAS  PubMed  Google Scholar 

  • Jakobs KH, Aktories K, Schultz G (1983) A nucleotide regulatory site for somatostatin inhibition of adenylate cyclase in S49 lymphoma cells. Nature 303:177–178

    Article  CAS  PubMed  Google Scholar 

  • 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 257:2829–2833

    CAS  PubMed  Google Scholar 

  • 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 2:381–392

    CAS  PubMed  Google Scholar 

  • Jakobs KH, Saur W, Schultz G (1978) Inhibition of platelet adenylate cyclase by epinephrine requires GTP. FEBS Lett 85:167–170

    Article  CAS  PubMed  Google Scholar 

  • Jakobs KH, Schultz G (1970) Effects of various hormones and drugs on adenyl cyclase of rat kidney. Naunyn-Schmiedebergs Archiv für Pharmakologie 266:364–365

    Article  CAS  PubMed  Google Scholar 

  • Jakobs KH, Schultz G (1980) Actions of hormones and neurotransmitters at the plasma membrane: inhibition of adenylate cyclase. Trends Pharmacol Sci 1:331–333

    Article  CAS  Google Scholar 

  • 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 80:3899–3902

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 273:248–266

    Article  CAS  Google Scholar 

  • 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 183:115–121

    Article  CAS  PubMed  Google Scholar 

  • 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 32:215–225

  • Jard S, Cantau B, Jakobs KH (1981) Angiotensin II and α-adrenergic agonists inhibit rat liver adenylate cyclase. J Biol Chem 256:2603–2606

    CAS  PubMed  Google Scholar 

  • 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 6:327–337

    Article  CAS  PubMed  Google Scholar 

  • 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 151:431–437

    Article  CAS  PubMed  Google Scholar 

  • 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 257:7210–7216

    CAS  PubMed  Google Scholar 

  • 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 161:149–152

    Article  CAS  PubMed  Google Scholar 

  • 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 76:1559–1565

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Katritch V, Cherezov V, Stevens RC (2013) Structure-function of the G protein-coupled receptor superfamily. Annu Rev Pharmacol Toxicol 53:531–556

    Article  CAS  PubMed  Google Scholar 

  • 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) 282:2275–2279

    Article  CAS  Google Scholar 

  • 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 279:46497–46508

    Article  CAS  PubMed  Google Scholar 

  • 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 128:4317–4327

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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) 280:2109–2111

    Article  CAS  Google Scholar 

  • 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 365:231–241

    Article  CAS  Google Scholar 

  • 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):429–434

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kupprion C, Wieland T, Jakobs KH (1993) Receptor-stimulated dissociation of GTP[S] from Gi-proteins in membranes of HL-60 cells. Cell Signal 5:425–433

    Article  CAS  PubMed  Google Scholar 

  • 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 261:6423–6428

    CAS  PubMed  Google Scholar 

  • 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 77:2500–2504

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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:E9

    Article  Google Scholar 

  • 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) 279:1552–1555

    Article  CAS  Google Scholar 

  • 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 80:429–440

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 128:1487–1498

    Article  CAS  PubMed  Google Scholar 

  • 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 345:7–15

    Article  CAS  Google Scholar 

  • Liebmann C, Schnittler M, Nawrath S, Jakobs KH (1991) High-affinity bradykinin receptor-catalyzed G protein activation in rat myometrium. Eur J Pharmacol 207:67–71

    Article  CAS  PubMed  Google Scholar 

  • 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 47:131–139

    CAS  PubMed  Google Scholar 

  • 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 269:21403–21406

    CAS  PubMed  Google Scholar 

  • Liu M, Simon MI (1996) Regulation by cAMP-dependent protein kinease of a G-protein-mediated phospholipase C. Nature 382:83–87

    Article  CAS  PubMed  Google Scholar 

  • 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) 337:232–236

    Article  CAS  Google Scholar 

  • 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 281:21837–21847

    Article  CAS  PubMed  Google Scholar 

  • 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 276:2758–2765

    Article  CAS  PubMed  Google Scholar 

  • 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 369:540–546

    Article  CAS  Google Scholar 

  • 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 280:11134–11139

    Article  CAS  PubMed  Google Scholar 

  • 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 25:630–638

    Article  CAS  PubMed  Google Scholar 

  • 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 49:48–55

    Article  CAS  PubMed  Google Scholar 

  • 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) 318:1923–1927

    Article  CAS  Google Scholar 

  • 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 87:305–313

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 59:4769–4777

    Article  CAS  PubMed  Google Scholar 

  • 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 102:959–965

    Article  CAS  PubMed  Google Scholar 

  • Meyer zu Heringdorf D (2004) Lysophospholipid receptor-dependent and -independent calcium signaling. J Cell Biochem 92:937–948

    Article  CAS  PubMed  Google Scholar 

  • Meyer zu Heringdorf D, Himmel HM, Jakobs KH (2002) Sphingosylphosphorylcholine-biological functions and mechanisms of action. Biochim Biophys Acta 1582:178–189

    Article  CAS  PubMed  Google Scholar 

  • Meyer zu Heringdorf D, Ihlefeld K, Pfeilschifter J (2013) Pharmacology of the sphingosine-1-phosphate signalling system. Handb Exp Pharmacol 239–253

  • 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 17:2830–2837

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 414:145–154

    Article  CAS  PubMed  Google Scholar 

  • 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 554:443–449

    Article  CAS  PubMed  Google Scholar 

  • 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 354:113–122

    Article  CAS  PubMed  Google Scholar 

  • 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 354:397–403

    Article  CAS  Google Scholar 

  • 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 15:677–687

    Article  CAS  Google Scholar 

  • 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:e66260

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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:e41876

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 29:552–558

    Article  CAS  Google Scholar 

  • 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):67

    Article  CAS  PubMed Central  Google Scholar 

  • 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):11062–11070

  • Motulsky HJ, Insel PA (1983) ADP- and epinephrine-elicited release of [3H]guanylylimidodiphosphate from platelet membranes Implications Recep-Ni Stoichiometry. FEBS Lett 164:13–16

    Article  CAS  PubMed  Google Scholar 

  • 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) 74:143–158

    Article  CAS  Google Scholar 

  • 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 35:11315–11329

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 126:3271–3277

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 93:848–856

    Article  CAS  PubMed  Google Scholar 

  • 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 258:11369–11376

    CAS  PubMed  Google Scholar 

  • 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 258:11361–11368

    CAS  PubMed  Google Scholar 

  • 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 77:6516–6520

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 45:890–898

    CAS  PubMed  Google Scholar 

  • 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:e31574

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 28:4617–4628

    Article  CAS  Google Scholar 

  • Olivera A, Spiegel S (1993) Sphingosine-1-phosphate as second messenger in cell proliferation induced by PDGF and FCS mitogens. Nature 365:557–560

    Article  CAS  Google Scholar 

  • 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 88:39–54

    Article  CAS  PubMed  Google Scholar 

  • 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 20:1018–1026

    Article  CAS  PubMed  Google Scholar 

  • Oude Weernink PA, Han L, Jakobs KH, Schmidt M (2007) Dynamic phospholipid signaling by G protein-coupled receptors. Biochim Biophys Acta 1768:888–900

    Article  CAS  PubMed  Google Scholar 

  • Oude Weernink PA, Schmidt M, Jakobs KH (2004) Regulation and cellular roles of phosphoinositide 5-kinases. Eur J Pharmacol 500:87–99

    Article  CAS  PubMed  Google Scholar 

  • 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 275:10168–10174

    Article  CAS  PubMed  Google Scholar 

  • Park D, Jhon DY, Lee CW, Lee KH, Rhee SG (1993) Activation of phospholipase C isozymes by G protein βγ subunits. J Biol Chem 268:4573–4576

    CAS  PubMed  Google Scholar 

  • 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 267:1496–1501

    CAS  PubMed  Google Scholar 

  • Parnell E, Palmer TM, Yarwood SJ (2015) The future of EPAC-targeted therapies: agonism versus antagonism. Trends Pharmacol Sci 36:203–214

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 79:7228–7232

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Proia RL, Hla T (2015) Emerging biology of sphingosine-1-phosphate: its role in pathogenesis and therapy. J Clin Invest 125:1379–1387

    Article  PubMed  PubMed Central  Google Scholar 

  • 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. 183-255

  • 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 100:1835–1844

    Article  CAS  PubMed  Google Scholar 

  • 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 477:549–555

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 98:13049–13054

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Robichaux WG 3rd, Cheng X (2018) Intracellular cAMP sensor EPAC: physiology, pathophysiology, and therapeutics development. Physiol Rev 98:919–1053

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 276:2474–2479

    Article  PubMed  Google Scholar 

  • 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 459:313–318

    Article  PubMed  Google Scholar 

  • 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 366:721–728

    Article  PubMed  PubMed Central  Google Scholar 

  • 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 234:240–244

    Article  PubMed  Google Scholar 

  • 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 361:1–11

    Article  Google Scholar 

  • 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 109:209–216

    Article  PubMed  Google Scholar 

  • 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):625–631

    Article  PubMed  PubMed Central  Google Scholar 

  • 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 248:407–414

    Article  PubMed  Google Scholar 

  • Sadana R, Dessauer CW (2009) Physiological roles for G protein-regulated adenylyl cyclase isoforms: insights from knockout and overexpression studies. Neuro-Signals 17:5–22

    Article  CAS  PubMed  Google Scholar 

  • Salomon MR, Bourne HR (1981) Novel S49 lymphoma variants with aberrant cyclic AMP metabolism. Mol Pharmacol 19:109–116

    CAS  PubMed  Google Scholar 

  • 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 103:662–678

    Article  CAS  PubMed  Google Scholar 

  • 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 225:667–675

    Article  CAS  PubMed  Google Scholar 

  • 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 352:469–476

    Article  CAS  Google Scholar 

  • 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 270:19949–19956

    Article  CAS  PubMed  Google Scholar 

  • 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 354:87–94

    Article  CAS  Google Scholar 

  • 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 271:2422–2426

    Article  CAS  PubMed  Google Scholar 

  • 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 240:707–712

    Article  CAS  PubMed  Google Scholar 

  • 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 273:7413–7422

    Article  CAS  PubMed  Google Scholar 

  • 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 3:1020–1024

    Article  CAS  PubMed  Google Scholar 

  • Schmidt M, Oude Weernink PA, Vom Dorp F, Stope MB, Jakobs KH (2004) Mammalian phospholipase C. Adv Mol Cell Biol 33:433–453

    Google Scholar 

  • Schmidt M, Sand C, Jakobs KH, Michel MC, Weernink PA (2007) Epac and the cardiovascular system. Curr Opin Pharmacol 7:193–200

    Article  CAS  PubMed  Google Scholar 

  • 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 65:670–709

    Article  CAS  PubMed  Google Scholar 

  • 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:e1002038

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 175:51–55

    Article  CAS  PubMed  Google Scholar 

  • 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 96:759–766

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 366:509–518

    Article  CAS  PubMed  Google Scholar 

  • 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 92:7242–7246

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smrcka AV, Brown JH, Holz GG (2012) Role of phospholipase Cε in physiological phosphoinositide signaling networks. Cell Signal 24:1333–1343

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 268:9667–9674

    CAS  PubMed  Google Scholar 

  • 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 278:21099–21104

    Article  CAS  PubMed  Google Scholar 

  • 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 34:1925–1933

    Article  CAS  Google Scholar 

  • 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 276:2752–2757

    Article  CAS  PubMed  Google Scholar 

  • Sternweis PC, Robishaw JD (1984) Isolation of two proteins with high affinity for guanine nucleotides from membranes of bovine brain. J Biol Chem 259:13806–13813

    CAS  PubMed  Google Scholar 

  • 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 24:4664–4676

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Strub GM, Maceyka M, Hait NC, Milstien S, Spiegel S (2010) Extracellular and intracellular actions of sphingosine-1-phosphate. Adv Exp Med Biol 688:141–155

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 288:16715–16725

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tanguy E, Kassas N, Vitale N (2018) Protein-phospholipd interaction motifs: a focus on phosphatidic acid. Biomolecules 8:20

  • 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 269:32175–32180

  • 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 1791:357–370

    Article  CAS  PubMed  Google Scholar 

  • 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:e50188

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 13:159–166

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thal DM, Glukhova A, Sexton PM, Christopoulos A (2018) Structural insights into G-protein-coupled receptor allostery. Nature 559:45–53

    Article  CAS  Google Scholar 

  • Tolkovsky AM, Levitzki A (1978) Mode of coupling between the β-adrenergic receptor and adenylate cyclase in turkey erythrocytes. Biochemistry 17:3795

    Article  CAS  PubMed  Google Scholar 

  • 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) 1:669–676

    Article  CAS  Google Scholar 

  • 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:e8536

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 271:2082–2087

    Article  PubMed  Google Scholar 

  • 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 49:956–961

    PubMed  Google Scholar 

  • 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 150:43–49

    Article  CAS  PubMed  Google Scholar 

  • 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 16:921–928

  • 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 274:34691–34698

    Article  CAS  PubMed  Google Scholar 

  • 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 97:1305–1313

    Article  CAS  PubMed  Google Scholar 

  • 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 113:9928–9933

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wettschureck N, Offermanns S (2005) Mammalian G proteins and their cell type specific functions. Physiol Rev 85:1159–1204

    Article  CAS  PubMed  Google Scholar 

  • 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 e255

    Article  CAS  Google Scholar 

  • Wieland C, Jakobs KH, Wieland T (1994) Altered guanine nucleoside triphosphate binding to transducin by cholera toxin-catalysed ADP-ribosylation. Cell Signal 6:487–492

    Article  CAS  PubMed  Google Scholar 

  • 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 208:17–23

    Article  CAS  PubMed  Google Scholar 

  • 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 360:14–26

    Article  CAS  Google Scholar 

  • 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 346:475–481

    Article  CAS  Google Scholar 

  • Wieland T, Jakobs KH (1989) Receptor-regulated formation of GTP[γS] with subsequent persistent Gs-protein activation in membranes of human platelets. FEBS Lett 245:189–193

    Article  CAS  PubMed  Google Scholar 

  • Wieland T, Jakobs KH (1992) Evidence for nucleoside diphosphokinase-dependent channeling of guanosine 5′-(γ-thio)triphosphate to guanine nucleotide-binding proteins. Mol Pharmacol 42:731–735

    CAS  PubMed  Google Scholar 

  • Wieland T, Jakobs KH (1994) Measurement of receptor-stimulated guanosine 5'-O-(γ-thio)triphosphate binding by G proteins. Methods Enzymol 237:3–13

    Article  CAS  Google Scholar 

  • 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 205:1201–1206

    Article  CAS  PubMed  Google Scholar 

  • 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 351:329–336

    Article  CAS  Google Scholar 

  • Wieland T, Mittmann C (2003) Regulators of G-protein signalling: multifunctional proteins with impact on signalling in the cardiovascular system. Pharmacol Ther 97:95–115

    Article  CAS  PubMed  Google Scholar 

  • 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 268:18111–18118

  • Wieland T, Ronzani M, Jakobs KH (1992c) Stimulation and inhibition of human platelet adenylylcyclase by thiophosphorylated transducin βγ-subunits. J Biol Chem 267:20791–20797

    CAS  PubMed  Google Scholar 

  • 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 196:707–716

    Article  CAS  PubMed  Google Scholar 

  • 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–Ii156

    CAS  Google Scholar 

  • Wuster M, Costa T, Aktories K, Jakobs KH (1984) Sodium regulation of opioid agonist binding is potentiated by pertussis toxin. Biochem Biophys Res Commun 123:1107–1115

    Article  CAS  PubMed  Google Scholar 

  • 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 277:11979–11986

    Article  CAS  PubMed  Google Scholar 

  • 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 22:1–9

    Article  CAS  Google Scholar 

  • 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:e002099

    Article  CAS  Google Scholar 

  • Zaccolo M, Magalhaes P, Pozzan T (2002) Compartmentalisation of cAMP and Ca2+ signals. Curr Opin Cell Biol 14:160–166

    Article  CAS  PubMed  Google Scholar 

  • 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) 21:740–752

    Article  CAS  Google Scholar 

  • 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 283:21036–21044

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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):605–609

    Article  CAS  PubMed  Google Scholar 

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  1. The authors are listed in alphabetical order to denote equal contribution

Authors and Affiliations

  1. Institute for Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, Albert Ludwigs University, 79104, Freiburg, Germany

    Klaus Aktories

  2. Institute of Pharmacology and Toxicology, Ulm University Medical Center, 89070, Ulm, Germany

    Peter Gierschik

  3. Institute of General Pharmacology and Toxicology, University Hospital Frankfurt am Main, Goethe University, 60590, Frankfurt am Main, Germany

    Dagmar Meyer zu Heringdorf

  4. Department of Molecular Pharmacology, University of Groningen, 9713AV, Groningen, The Netherlands

    Martina Schmidt

  5. Department of Pharmacology, Charité University Medical Center Berlin, Campus Benjamin Franklin, 14195, Berlin, Germany

    Günter Schultz

  6. Experimental Pharmacology Mannheim (EPM), European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Ludolf-Krehl-Str. 13 - 17, 68167, Mannheim, Germany

    Thomas Wieland

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

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Aktories, K., Gierschik, P., Heringdorf, D.M.z. et al. cAMP guided his way: a life for G protein-mediated signal transduction and molecular pharmacology—tribute to Karl H. Jakobs. Naunyn-Schmiedeberg's Arch Pharmacol 392, 887–911 (2019). https://doi.org/10.1007/s00210-019-01650-1

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