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cGMP-Dependent Protein Kinases (cGK)

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Guanylate Cyclase and Cyclic GMP

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1020))

Abstract

cGMP-dependent protein kinases (cGK) are serine/threonine kinases that are widely distributed in eukaryotes. Two genes—prkg1 and prkg2—code for cGKs, namely, cGKI and cGKII. In mammals, two isozymes, cGKIα and cGKIβ, are generated from the prkg1 gene. The cGKI isozymes are prominent in all types of smooth muscle, platelets, and specific neuronal areas such as cerebellar Purkinje cells, hippocampal neurons, and the lateral amygdala. The cGKII prevails in the secretory epithelium of the small intestine, the juxtaglomerular cells, the adrenal cortex, the chondrocytes, and in the nucleus suprachiasmaticus. Both cGKs are major downstream effectors of many, but not all, signalling events of the NO/cGMP and the ANP/cGMP pathways. cGKI relaxes smooth muscle tone and prevents platelet aggregation, whereas cGKII inhibits renin secretion, chloride/water secretion in the small intestine, the resetting of the clock during early night, and endochondral bone growth. This chapter focuses on the involvement of cGKs in cardiovascular and non-cardiovascular processes including cell growth and metabolism.

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References

  1. Friebe A, Koesling D (2003) Regulation of nitric oxide-sensitive guanylyl cyclase. Circ Res 93(2):96–105

    Article  PubMed  CAS  Google Scholar 

  2. Katsuki S, Arnold W, Mittal C, Murad F (1977) Stimulation of guanylate cyclase by sodium nitroprusside, nitroglycerin and nitric oxide in various tissue preparations and comparison to the effects of sodium azide and hydroxylamine. J Cyclic Nucleotide Res 3(1):23–35

    PubMed  CAS  Google Scholar 

  3. Garbers DL (1992) Guanylyl cyclase receptors and their endocrine, paracrine, and autocrine ligands. Cell 71(1):1–4

    Article  PubMed  CAS  Google Scholar 

  4. Rybalkin SD, Yan C, Bornfeldt KE, Beavo JA (2003) Cyclic GMP phosphodiesterases and regulation of smooth muscle function. Circ Res 93(4):280–291

    Article  PubMed  CAS  Google Scholar 

  5. Bender AT, Beavo JA (2006) Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use. Pharmacol Rev 58(3):488–520

    Article  PubMed  CAS  Google Scholar 

  6. Biel M, Zong X, Ludwig A, Sautter A, Hofmann F (1999) Structure and function of cyclic nucleotide-gated channels. Rev Physiol Biochem Pharmacol 135:151–171

    Article  PubMed  CAS  Google Scholar 

  7. Hofmann F, Biel M, Feil R, Kleppisch T (2004) Mouse models of NO/natriuretic peptide/cGMP kinase signaling. In: Offermanns S (ed) Handbook of experimental pharmacology, vol 159, Transgenic models in pharmacology. Elsevier, Amsterdam, pp 95–130

    Google Scholar 

  8. Hofmann F (2005) The biology of cyclic GMP-dependent protein kinases. J Biol Chem 280(1):1–4

    PubMed  CAS  Google Scholar 

  9. Pfeifer A, Ruth P, Dostmann W, Sausbier M, Klatt P, Hofmann F (1999) Structure and function of cGMP-dependent protein kinases. Rev Physiol Biochem Pharmacol 135:105–149

    Article  PubMed  CAS  Google Scholar 

  10. Feil R, Lohmann SM, de Jonge H, Walter U, Hofmann F (2003) Cyclic GMP-dependent protein kinases and the cardiovascular system: insights from genetically modified mice. Circ Res 93(10):907–916

    Article  PubMed  CAS  Google Scholar 

  11. Hess DT, Matsumoto A, Kim SO, Marshall HE, Stamler JS (2005) Protein S-nitrosylation: purview and parameters. Nat Rev Mol Cell Biol 6(2):150–166

    Article  PubMed  CAS  Google Scholar 

  12. Burkhardt M, Glazova M, Gambaryan S, Vollkommer T, Butt E, Bader B, Heermeier K, Lincoln TM, Walter U, Palmetshofer A (2000) KT5823 inhibits cGMP-dependent protein kinase activity in vitro but not in intact human platelets and rat mesangial cells. J Biol Chem 275(43):33536–33541

    Article  PubMed  CAS  Google Scholar 

  13. Marshall SJ, Senis YA, Auger JM, Feil R, Hofmann F, Salmon G, Peterson JT, Burslem F, Watson SP (2004) GPIb-dependent platelet activation is dependent on Src kinases but not MAP kinase or cGMP-dependent kinase. Blood 103(7):2601–2609

    Article  PubMed  CAS  Google Scholar 

  14. Wyatt TA, Pryzwansky KB, Lincoln TM (1991) KT5823 activates human neutrophils and fails to inhibit cGMP-dependent protein kinase phosphorylation of vimentin. Res Commun Chem Pathol Pharmacol 74(1):3–14

    PubMed  CAS  Google Scholar 

  15. Daugirdas JT, Zhou HL, Tamulaitis VV, Nutting CW, Fiscus RR (1991) Effect of H-8, an isoquinolinesulfonamide inhibitor of cyclic nucleotide-dependent protein kinase, on cAMP- and cGMP-mediated vasorelaxation. Blood Vessels 28(5):366–371

    PubMed  CAS  Google Scholar 

  16. Valtcheva N, Nestorov P, Beck A, Russwurm M, Hillenbrand M, Weinmeister P, Feil R (2009) The commonly used cGMP-dependent protein kinase type I (cGKI) inhibitor Rp-8-Br-PET-cGMPS can activate cGKI in vitro and in intact cells. J Biol Chem 284(1):556–562. doi:10.1074/jbc.M806161200

    Article  PubMed  CAS  Google Scholar 

  17. Hofmann F, Bernhard D, Lukowski R, Weinmeister P (2009) cGMP regulated protein kinases (cGK). Handb Exp Pharmacol 191:137–162

    Article  PubMed  CAS  Google Scholar 

  18. Francis SH, Busch JL, Corbin JD, Sibley D (2010) cGMP-dependent protein kinases and cGMP phosphodiesterases in nitric oxide and cGMP action. Pharmacol Rev 62(3):525–563

    Article  PubMed  CAS  Google Scholar 

  19. D’Souza SP, Davis M, Baxter GF (2004) Autocrine and paracrine actions of natriuretic peptides in the heart. Pharmacol Ther 101(2):113–129

    Article  PubMed  CAS  Google Scholar 

  20. Garbers DL, Dubois SK (1999) The molecular basis of hypertension. Annu Rev Biochem 68:127–155

    Article  PubMed  CAS  Google Scholar 

  21. Lloyd-Jones DM, Bloch KD (1996) The vascular biology of nitric oxide and its role in atherogenesis. Annu Rev Med 47:365–375

    Article  PubMed  CAS  Google Scholar 

  22. Massion PB, Feron O, Dessy C, Balligand JL (2003) Nitric oxide and cardiac function: ten years after, and continuing. Circ Res 93(5):388–398

    Article  PubMed  CAS  Google Scholar 

  23. Ignarro LJ (2002) Nitric oxide as a unique signaling molecule in the vascular system: a historical overview. J Physiol Pharmacol 53(4 Pt 1):503–514

    PubMed  CAS  Google Scholar 

  24. Shimokawa H, Tsutsui M (2010) Nitric oxide synthases in the pathogenesis of cardiovascular disease: lessons from genetically modified mice. Pflugers Arch 459(6):959–967. doi:10.1007/s00424-010-0796-2

    Article  PubMed  CAS  Google Scholar 

  25. Ziolo MT, Kohr MJ, Wang H (2008) Nitric oxide signaling and the regulation of myocardial function. J Mol Cell Cardiol 45(5):625–632. doi:10.1016/j.yjmcc.2008.07.015

    Article  PubMed  CAS  Google Scholar 

  26. Abassi Z, Karram T, Ellaham S, Winaver J, Hoffman A (2004) Implications of the natriuretic peptide system in the pathogenesis of heart failure: diagnostic and therapeutic importance. Pharmacol Ther 102(3):223–241. doi:10.1016/j.pharmthera.2004.04.004

    Article  PubMed  CAS  Google Scholar 

  27. Roy LF, Ogilvie RI, Larochelle P, Hamet P, Leenen FH (1989) Cardiac and vascular effects of atrial natriuretic factor and sodium nitroprusside in healthy men. Circulation 79(2):383–392

    Article  PubMed  CAS  Google Scholar 

  28. Moncada S, Higgs A (1993) The l-arginine-nitric oxide pathway. N Engl J Med 329(27):2002–2012. doi:10.1056/NEJM199312303292706

    Article  PubMed  CAS  Google Scholar 

  29. Matsumoto T, Wada A, Tsutamoto T, Omura T, Yokohama H, Ohnishi M, Nakae I, Takahashi M, Kinoshita M (1999) Vasorelaxing effects of atrial and brain natriuretic peptides on coronary circulation in heart failure. Am J Physiol 276(6 Pt 2):H1935–H1942

    PubMed  CAS  Google Scholar 

  30. Winquist RJ, Faison EP, Waldman SA, Schwartz K, Murad F, Rapoport RM (1984) Atrial natriuretic factor elicits an endothelium-independent relaxation and activates particulate guanylate cyclase in vascular smooth muscle. Proc Natl Acad Sci USA 81(23):7661–7664

    Article  PubMed  CAS  Google Scholar 

  31. Inagami T (1994) Atrial natriuretic factor as a volume regulator. J Clin Pharmacol 34(5):424–426

    Article  PubMed  CAS  Google Scholar 

  32. Ishibashi T, Hamaguchi M, Kato K, Kawada T, Ohta H, Sasage H, Imai S (1993) Relationship between myoglobin contents and increases in cyclic GMP produced by glyceryl trinitrate and nitric oxide in rabbit aorta, right atrium and papillary muscle. Naunyn Schmiedebergs Arch Pharmacol 347(5):553–561

    Article  PubMed  CAS  Google Scholar 

  33. Yanagisawa T, Hashimoto H, Taira N (1988) The negative inotropic effect of nicorandil is independent of cyclic GMP changes: a comparison with pinacidil and cromakalim in canine atrial muscle. Br J Pharmacol 95(2):393–398

    Article  PubMed  CAS  Google Scholar 

  34. Cramb G, Banks R, Rugg EL, Aiton JF (1987) Actions of atrial natriuretic peptide (ANP) on cyclic nucleotide concentrations and phosphatidylinositol turnover in ventricular myocytes. Biochem Biophys Res Commun 148(3):962–970

    Article  PubMed  CAS  Google Scholar 

  35. Mullershausen F, Friebe A, Feil R, Thompson WJ, Hofmann F, Koesling D (2003) Direct activation of PDE5 by cGMP: long-term effects within NO/cGMP signaling. J Cell Biol 160(5):719–727

    Article  PubMed  CAS  Google Scholar 

  36. Kuhn M (2003) Structure, regulation, and function of mammalian membrane guanylyl cyclase receptors, with a focus on guanylyl cyclase-A. Circ Res 93(8):700–709

    Article  PubMed  CAS  Google Scholar 

  37. Francis SH, Busch JL, Corbin JD, Sibley D (2010) cGMP-dependent protein kinases and cGMP phosphodiesterases in nitric oxide and cGMP action. Pharmacol Rev 62(3):525–563. doi:10.1124/pr.110.002907

    Article  PubMed  CAS  Google Scholar 

  38. Ecker T, Gobel C, Hullin R, Rettig R, Seitz G, Hofmann F (1989) Decreased cardiac concentration of cGMP kinase in hypertensive animals. An index for cardiac vascularization? Circ Res 65(5):1361–1369

    Article  PubMed  CAS  Google Scholar 

  39. Wegener JW, Nawrath H, Wolfsgruber W, Kuhbandner S, Werner C, Hofmann F, Feil R (2002) cGMP-dependent protein kinase I mediates the negative inotropic effect of cGMP in the murine myocardium. Circ Res 90(1):18–20

    Article  PubMed  CAS  Google Scholar 

  40. Takimoto E, Champion HC, Li M, Belardi D, Ren S, Rodriguez ER, Bedja D, Gabrielson KL, Wang Y, Kass DA (2005) Chronic inhibition of cyclic GMP phosphodiesterase 5A prevents and reverses cardiac hypertrophy. Nat Med 11(2):214–222

    Article  PubMed  CAS  Google Scholar 

  41. MacDonell KL, Diamond J (1997) Cyclic GMP-dependent protein kinase activation in the absence of negative inotropic effects in the rat ventricle. Br J Pharmacol 122(7):1425–1435. doi:10.1038/sj.bjp.0701492

    Article  PubMed  CAS  Google Scholar 

  42. Pierkes M, Gambaryan S, Boknik P, Lohmann SM, Schmitz W, Potthast R, Holtwick R, Kuhn M (2002) Increased effects of C-type natriuretic peptide on cardiac ventricular contractility and relaxation in guanylyl cyclase A-deficient mice. Cardiovasc Res 53(4):852–861

    Article  PubMed  CAS  Google Scholar 

  43. Lukowski R, Rybalkin SD, Loga F, Leiss V, Beavo JA, Hofmann F (2010) Cardiac hypertrophy is not amplified by deletion of cGMP-dependent protein kinase I in cardiomyocytes. Proc Natl Acad Sci USA 107(12):5646–5651. doi:10.1073/pnas.1001360107

    Article  PubMed  CAS  Google Scholar 

  44. Mery PF, Lohmann SM, Walter U, Fischmeister R (1991) Ca2+ current is regulated by cyclic GMP-dependent protein kinase in mammalian cardiac myocytes. Proc Natl Acad Sci USA 88(4):1197–1201

    Article  PubMed  CAS  Google Scholar 

  45. George WJ, Polson JB, O’Toole AG, Goldberg ND (1970) Elevation of guanosine 3′,5′-cyclic phosphate in rat heart after perfusion with acetylcholine. Proc Natl Acad Sci USA 66(2):398–403

    Article  PubMed  CAS  Google Scholar 

  46. Watanabe AM, Besch HR Jr (1975) Interaction between cyclic adenosine monophosphate and cyclic gunaosine monophosphate in guinea pig ventricular myocardium. Circ Res 37(3):309–317

    Article  PubMed  CAS  Google Scholar 

  47. MacDonell KL, Tibbits GF, Diamond J (1995) cGMP elevation does not mediate muscarinic agonist-induced negative inotropy in rat ventricular cardiomyocytes. Am J Physiol 269(6 Pt 2):H1905–H1912

    PubMed  CAS  Google Scholar 

  48. Hayek S, Nemer M (2011) Cardiac natriuretic peptides: from basic discovery to ­clinical practice. Cardiovasc Ther 29(6):362–376. doi:10.1111/j.1755-5922.2010.00152.x

    Article  PubMed  CAS  Google Scholar 

  49. Wegener JW, Gath I, Forstermann U, Nawrath H (1997) Activation of soluble guanylyl cyclase by YC-1 in aortic smooth muscle but not in ventricular myocardium from rat. Br J Pharmacol 122(7):1523–1529. doi:10.1038/sj.bjp.0701542

    Article  PubMed  CAS  Google Scholar 

  50. Rosenkranz AC, Woods RL, Dusting GJ, Ritchie RH (2003) Antihypertrophic actions of the natriuretic peptides in adult rat cardiomyocytes: importance of cyclic GMP. Cardiovasc Res 57(2):515–522

    Article  PubMed  CAS  Google Scholar 

  51. Hiwatari M, Satoh K, Angus JA, Johnston CI (1986) No effect of atrial natriuretic factor on cardiac rate, force and transmitter release. Clin Exp Pharmacol Physiol 13(2):163–168

    Article  PubMed  CAS  Google Scholar 

  52. Bergey JL, Kotler D (1985) Effects of atriopeptins I, II and III on atrial contractility, sinus nodal rate (guinea pig) and agonist-induced tension in rabbit aortic strips. Eur J Pharmacol 110(2):277–281

    Article  PubMed  CAS  Google Scholar 

  53. Bohm M, Diet F, Pieske B, Erdmann E (1988) h-ANF does not play a role in the regulation of myocardial force of contraction. Life Sci 43(16):1261–1267

    Article  PubMed  CAS  Google Scholar 

  54. Neyses L, Vetter H (1989) Action of atrial natriuretic peptide and angiotensin II on the myocardium: studies in isolated rat ventricular cardiomyocytes. Biochem Biophys Res Commun 163(3):1435–1443

    Article  PubMed  CAS  Google Scholar 

  55. Brusq JM, Mayoux E, Guigui L, Kirilovsky J (1999) Effects of C-type natriuretic peptide on rat cardiac contractility. Br J Pharmacol 128(1):206–212. doi:10.1038/sj.bjp.0702766

    Article  PubMed  CAS  Google Scholar 

  56. Wollert KC, Yurukova S, Kilic A, Begrow F, Fiedler B, Gambaryan S, Walter U, Lohmann SM, Kuhn M (2003) Increased effects of C-type natriuretic peptide on contractility and calcium regulation in murine hearts overexpressing cyclic GMP-dependent protein kinase I. Br J Pharmacol 140(7):1227–1236

    Article  PubMed  CAS  Google Scholar 

  57. Castro LR, Schittl J, Fischmeister R (2010) Feedback control through cGMP-dependent protein kinase contributes to differential regulation and compartmentation of cGMP in rat cardiac myocytes. Circ Res 107(10):1232–1240. doi:10.1161/CIRCRESAHA.110.226712

    Article  PubMed  CAS  Google Scholar 

  58. Piggott LA, Hassell KA, Berkova Z, Morris AP, Silberbach M, Rich TC (2006) Natriuretic peptides and nitric oxide stimulate cGMP synthesis in different cellular compartments. J Gen Physiol 128(1):3–14. doi:10.1085/jgp.200509403

    Article  PubMed  CAS  Google Scholar 

  59. Hare JM, Stamler JS (2005) NO/redox disequilibrium in the failing heart and cardiovascular system. J Clin Invest 115(3):509–517

    PubMed  CAS  Google Scholar 

  60. Ziolo MT (2008) The fork in the nitric oxide road: cyclic GMP or nitrosylation? Nitric Oxide 18(3):153–156. doi:10.1016/j.niox.2008.01.008

    Article  PubMed  CAS  Google Scholar 

  61. Hendgen-Cotta UB, Flogel U, Kelm M, Rassaf T (2010) Unmasking the Janus face of myoglobin in health and disease. J Exp Biol 213(Pt 16):2734–2740. doi:10.1242/jeb.041178

    Article  PubMed  CAS  Google Scholar 

  62. Wegener JW, Godecke A, Schrader J, Nawrath H (2002) Effects of nitric oxide donors on cardiac contractility in wild-type and myoglobin-deficient mice. Br J Pharmacol 136(3):415–420. doi:10.1038/sj.bjp.0704740

    Article  PubMed  CAS  Google Scholar 

  63. Maulik N, Engelman DT, Watanabe M, Engelman RM, Maulik G, Cordis GA, Das DK (1995) Nitric oxide signaling in ischemic heart. Cardiovasc Res 30(4):593–601

    PubMed  CAS  Google Scholar 

  64. Kojda G, Kottenberg K, Nix P, Schluter KD, Piper HM, Noack E (1996) Low increase in cGMP induced by organic nitrates and nitrovasodilators improves contractile response of rat ventricular myocytes. Circ Res 78(1):91–101

    Article  PubMed  CAS  Google Scholar 

  65. Kohr MJ, Wang H, Wheeler DG, Velayutham M, Zweier JL, Ziolo MT (2008) Biphasic effect of SIN-1 is reliant upon cardiomyocyte contractile state. Free Radic Biol Med 45(1):73–80. doi:10.1016/j.freeradbiomed.2008.03.019

    Article  PubMed  CAS  Google Scholar 

  66. Han X, Kubota I, Feron O, Opel DJ, Arstall MA, Zhao YY, Huang P, Fishman MC, Michel T, Kelly RA (1998) Muscarinic cholinergic regulation of cardiac myocyte ICa-L is absent in mice with targeted disruption of endothelial nitric oxide synthase. Proc Natl Acad Sci USA 95(11):6510–6515

    Article  PubMed  CAS  Google Scholar 

  67. Hare JM, Colucci WS (1995) Role of nitric oxide in the regulation of myocardial function. Prog Cardiovasc Dis 38(2):155–166

    Article  PubMed  CAS  Google Scholar 

  68. Vandecasteele G, Eschenhagen T, Scholz H, Stein B, Verde I, Fischmeister R (1999) Muscarinic and beta-adrenergic regulation of heart rate, force of contraction and calcium current is preserved in mice lacking endothelial nitric oxide synthase. Nat Med 5(3):331–334

    Article  PubMed  CAS  Google Scholar 

  69. Godecke A, Heinicke T, Kamkin A, Kiseleva I, Strasser RH, Decking UK, Stumpe T, Isenberg G, Schrader J (2001) Inotropic response to beta-adrenergic receptor stimulation and anti- adrenergic effect of ACh in endothelial NO synthase-deficient mouse hearts. J Physiol 532(Pt 1):195–204

    Article  PubMed  CAS  Google Scholar 

  70. Yang L, Liu G, Zakharov SI, Bellinger AM, Mongillo M, Marx SO (2007) Protein kinase G phosphorylates Cav1.2 alpha1c and beta2 subunits. Circ Res 101(5):465–474

    Article  PubMed  CAS  Google Scholar 

  71. Rodriguez-Pascual F, Ferrero R, Miras-Portugal MT, Torres M (1999) Phosphorylation of tyrosine hydroxylase by cGMP-dependent protein kinase in intact bovine chromaffin cells. Arch Biochem Biophys 366(2):207–214. doi:10.1006/abbi.1999.1199

    Article  PubMed  CAS  Google Scholar 

  72. Wang Y, Wagner MB, Joyner RW, Kumar R (2000) cGMP-dependent protein kinase mediates stimulation of l-type calcium current by cGMP in rabbit atrial cells. Cardiovasc Res 48(2):310–322

    Article  PubMed  CAS  Google Scholar 

  73. Wahler GM, Dollinger SJ (1995) Nitric oxide donor SIN-1 inhibits mammalian cardiac calcium current through cGMP-dependent protein kinase. Am J Physiol 268(1 Pt 1):C45–C54

    PubMed  CAS  Google Scholar 

  74. Schroder F, Klein G, Fiedler B, Bastein M, Schnasse N, Hillmer A, Ames S, Gambaryan S, Drexler H, Walter U, Lohmann SM, Wollert KC (2003) Single l-type Ca(2+) channel regulation by cGMP-dependent protein kinase type I in adult cardiomyocytes from PKG I transgenic mice. Cardiovasc Res 60(2):268–277

    Article  PubMed  CAS  Google Scholar 

  75. Fischmeister R, Castro L, Abi-Gerges A, Rochais F, Vandecasteele G (2005) Species- and tissue-dependent effects of NO and cyclic GMP on cardiac ion channels. Comp Biochem Physiol A Mol Integr Physiol 142(2):136–143. doi:10.1016/j.cbpb.2005.04.012

    Article  PubMed  CAS  Google Scholar 

  76. Fischmeister R, Castro LR, Abi-Gerges A, Rochais F, Jurevicius J, Leroy J, Vandecasteele G (2006) Compartmentation of cyclic nucleotide signaling in the heart: the role of cyclic nucleotide phosphodiesterases. Circ Res 99(8):816–828. doi:10.1161/01.RES.0000246118.98832.04

    Article  PubMed  CAS  Google Scholar 

  77. Zhang M, Takimoto E, Lee DI, Santos CX, Nakamura T, Hsu S, Jiang A, Nagayama T, Bedja D, Yuan Y, Eaton P, Shah AM, Kass DA (2012) Pathological cardiac hypertrophy alters intracellular targeting of phosphodiesterase type 5 from nitric oxide synthase-3 to natriuretic Peptide signaling. Circulation 126(8):942–951

    Article  PubMed  CAS  Google Scholar 

  78. Jiang H, Colbran JL, Francis SH, Corbin JD (1992) Direct evidence for cross-activation of cGMP-dependent protein kinase by cAMP in pig coronary arteries. J Biol Chem 267(2):1015–1019

    PubMed  CAS  Google Scholar 

  79. Kruger M, Kotter S, Grutzner A, Lang P, Andresen C, Redfield MM, Butt E, dos Remedios CG, Linke WA (2009) Protein kinase G modulates human myocardial passive stiffness by phosphorylation of the titin springs. Circ Res 104(1):87–94. doi:10.1161/CIRCRESAHA.108.184408

    Article  PubMed  CAS  Google Scholar 

  80. LeWinter MM, Granzier H (2010) Cardiac titin: a multifunctional giant. Circulation 121(19):2137–2145. doi:10.1161/CIRCULATIONAHA.109.860171

    Article  PubMed  Google Scholar 

  81. Voelkel T, Linke WA (2011) Conformation-regulated mechanosensory control via titin domains in cardiac muscle. Pflugers Arch 462(1):143–154. doi:10.1007/s00424-011-0938-1

    Article  PubMed  CAS  Google Scholar 

  82. Lee EJ, Peng J, Radke M, Gotthardt M, Granzier HL (2010) Calcium sensitivity and the Frank-Starling mechanism of the heart are increased in titin N2B region-deficient mice. J Mol Cell Cardiol 49(3):449–458. doi:10.1016/j.yjmcc.2010.05.006

    Article  PubMed  CAS  Google Scholar 

  83. Terui T, Sodnomtseren M, Matsuba D, Udaka J, Ishiwata S, Ohtsuki I, Kurihara S, Fukuda N (2008) Troponin and titin coordinately regulate length-dependent activation in skinned porcine ventricular muscle. J Gen Physiol 131(3):275–283. doi:10.1085/jgp.200709895

    Article  PubMed  CAS  Google Scholar 

  84. Borbely A, Falcao-Pires I, van Heerebeek L, Hamdani N, Edes I, Gavina C, Leite-Moreira AF, Bronzwaer JG, Papp Z, van der Velden J, Stienen GJ, Paulus WJ (2009) Hypophosphorylation of the Stiff N2B titin isoform raises cardiomyocyte resting tension in failing human myocardium. Circ Res 104(6):780–786. doi:10.1161/CIRCRESAHA.108.193326

    Article  PubMed  CAS  Google Scholar 

  85. van Heerebeek L, Hamdani N, Falcao-Pires I, Leite-Moreira AF, Begieneman MP, Bronzwaer JG, van der Velden J, Stienen GJ, Laarman GJ, Somsen A, Verheugt FW, Niessen HW, Paulus WJ (2012) Low myocardial protein kinase g activity in heart failure with preserved ejection fraction. Circulation 126(7):830–839. doi:10.1161/CIRCULATIONAHA.111.076075

    Article  PubMed  CAS  Google Scholar 

  86. Bishu K, Hamdani N, Mohammed SF, Kruger M, Ohtani T, Ogut O, Brozovich FV, Burnett JC Jr, Linke WA, Redfield MM (2011) Sildenafil and B-type natriuretic peptide acutely phosphorylate titin and improve diastolic distensibility in vivo. Circulation 124(25):2882–2891. doi:10.1161/CIRCULATIONAHA.111.048520

    Article  PubMed  CAS  Google Scholar 

  87. Kruger M, Linke WA (2006) Protein kinase-A phosphorylates titin in human heart muscle and reduces myofibrillar passive tension. J Muscle Res Cell Motil 27(5–7):435–444. doi:10.1007/s10974-006-9090-5

    Article  PubMed  CAS  Google Scholar 

  88. Yamasaki R, Wu Y, McNabb M, Greaser M, Labeit S, Granzier H (2002) Protein kinase A phosphorylates titin’s cardiac-specific N2B domain and reduces passive tension in rat cardiac myocytes. Circ Res 90(11):1181–1188

    Article  PubMed  CAS  Google Scholar 

  89. Jessup M, Brozena S (2003) Heart failure. N Engl J Med 348(20):2007–2018. doi:10.1056/NEJMra021498

    Article  PubMed  Google Scholar 

  90. Zamanillo D, Sprengel R, Hvalby O, Jensen V, Burnashev N, Rozov A, Kaiser KM, Koster HJ, Borchardt T, Worley P, Lubke J, Frotscher M, Kelly PH, Sommer B, Andersen P, Seeburg PH, Sakmann B (1999) Importance of AMPA receptors for hippocampal synaptic plasticity but not for spatial learning. Science 284(5421):1805–1811

    Article  PubMed  CAS  Google Scholar 

  91. Shah AM, Mann DL (2011) In search of new therapeutic targets and strategies for heart failure: recent advances in basic science. Lancet 378(9792):704–712. doi:10.1016/S0140-6736(11)60894-5

    Article  PubMed  CAS  Google Scholar 

  92. John SW, Krege JH, Oliver PM, Hagaman JR, Hodgin JB, Pang SC, Flynn TG, Smithies O (1995) Genetic decreases in atrial natriuretic peptide and salt-sensitive hypertension. Science 267(5198):679–681

    Article  PubMed  CAS  Google Scholar 

  93. Oliver PM, Fox JE, Kim R, Rockman HA, Kim HS, Reddick RL, Pandey KN, Milgram SL, Smithies O, Maeda N (1997) Hypertension, cardiac hypertrophy, and sudden death in mice lacking natriuretic peptide receptor A. Proc Natl Acad Sci USA 94(26):14730–14735

    Article  PubMed  CAS  Google Scholar 

  94. Kishimoto I, Rossi K, Garbers DL (2001) A genetic model provides evidence that the receptor for atrial natriuretic peptide (guanylyl cyclase-A) inhibits cardiac ventricular myocyte hypertrophy. Proc Natl Acad Sci USA 98(5):2703–2706

    Article  PubMed  CAS  Google Scholar 

  95. Knowles JW, Esposito G, Mao L, Hagaman JR, Fox JE, Smithies O, Rockman HA, Maeda N (2001) Pressure-independent enhancement of cardiac hypertrophy in natriuretic peptide receptor A-deficient mice. J Clin Invest 107(8):975–984

    Article  PubMed  CAS  Google Scholar 

  96. Holtwick R, Van Eickels M, Skryabin BV, Baba HA, Bubikat A, Begrow F, Schneider MD, Garbers DL, Kuhn M (2003) Pressure-independent cardiac hypertrophy in mice with cardiomyocyte-restricted inactivation of the atrial natriuretic peptide receptor guanylyl cyclase-A. J Clin Invest 111(9):1399–1407

    PubMed  CAS  Google Scholar 

  97. Ruetten H, Dimmeler S, Gehring D, Ihling C, Zeiher AM (2005) Concentric left ventricular remodeling in endothelial nitric oxide synthase knockout mice by chronic pressure overload. Cardiovasc Res 66(3):444–453. doi:10.1016/j.cardiores.2005.01.021

    Article  PubMed  CAS  Google Scholar 

  98. Wenzel S, Rohde C, Wingerning S, Roth J, Kojda G, Schluter KD (2007) Lack of endothelial nitric oxide synthase-derived nitric oxide formation favors hypertrophy in adult ventricular cardiomyocytes. Hypertension 49(1):193–200. doi:10.1161/01.HYP.0000250468.02084.ce

    Article  PubMed  CAS  Google Scholar 

  99. Flaherty MP, Brown M, Grupp IL, Schultz JE, Murphree SS, Jones WK (2007) eNOS deficient mice develop progressive cardiac hypertrophy with altered cytokine and calcium handling protein expression. Cardiovasc Toxicol 7(3):165–177. doi:10.1007/s12012-007-0028-y

    Article  PubMed  CAS  Google Scholar 

  100. Janssens S, Pokreisz P, Schoonjans L, Pellens M, Vermeersch P, Tjwa M, Jans P, Scherrer-Crosbie M, Picard MH, Szelid Z, Gillijns H, Van de Werf F, Collen D, Bloch KD (2004) Cardiomyocyte-specific overexpression of nitric oxide synthase 3 improves left ventricular performance and reduces compensatory hypertrophy after myocardial infarction. Circ Res 94(9):1256–1262. doi:10.1161/01.RES.0000126497.38281.23

    Article  PubMed  CAS  Google Scholar 

  101. Calderone A, Thaik CM, Takahashi N, Chang DL, Colucci WS (1998) Nitric oxide, atrial natriuretic peptide, and cyclic GMP inhibit the growth-promoting effects of norepinephrine in cardiac myocytes and fibroblasts. J Clin Invest 101(4):812–818

    Article  PubMed  CAS  Google Scholar 

  102. Horio T, Nishikimi T, Yoshihara F, Matsuo H, Takishita S, Kangawa K (2000) Inhibitory regulation of hypertrophy by endogenous atrial natriuretic peptide in cultured cardiac myocytes. Hypertension 35(1 Pt 1):19–24

    Article  PubMed  CAS  Google Scholar 

  103. Laskowski A, Woodman OL, Cao AH, Drummond GR, Marshall T, Kaye DM, Ritchie RH (2006) Antioxidant actions contribute to the antihypertrophic effects of atrial natriuretic peptide in neonatal rat cardiomyocytes. Cardiovasc Res 72(1):112–123. doi:10.1016/j.cardiores.2006.07.006

    Article  PubMed  CAS  Google Scholar 

  104. Nakamura TY, Iwata Y, Arai Y, Komamura K, Wakabayashi S (2008) Activation of Na+/H+ exchanger 1 is sufficient to generate Ca2+ signals that induce cardiac hypertrophy and heart failure. Circ Res 103(8):891–899. doi:10.1161/CIRCRESAHA.108.175141

    Article  PubMed  CAS  Google Scholar 

  105. Nakayama H, Wilkin BJ, Bodi I, Molkentin JD (2006) Calcineurin-dependent cardiomyopathy is activated by TRPC in the adult mouse heart. FASEB J 20(10):1660–1670. doi:10.1096/fj.05-5560com

    Article  PubMed  CAS  Google Scholar 

  106. De Windt LJ, Lim HW, Bueno OF, Liang Q, Delling U, Braz JC, Glascock BJ, Kimball TF, del Monte F, Hajjar RJ, Molkentin JD (2001) Targeted inhibition of calcineurin attenuates cardiac hypertrophy in vivo. Proc Natl Acad Sci USA 98(6):3322–3327. doi:10.1073/pnas.031371998

    Article  PubMed  Google Scholar 

  107. Backs J, Backs T, Neef S, Kreusser MM, Lehmann LH, Patrick DM, Grueter CE, Qi X, Richardson JA, Hill JA, Katus HA, Bassel-Duby R, Maier LS, Olson EN (2009) The delta isoform of CaM kinase II is required for pathological cardiac hypertrophy and remodeling after pressure overload. Proc Natl Acad Sci USA 106(7):2342–2347. doi:10.1073/pnas.0813013106

    Article  PubMed  CAS  Google Scholar 

  108. Condorelli G, Drusco A, Stassi G, Bellacosa A, Roncarati R, Iaccarino G, Russo MA, Gu Y, Dalton N, Chung C, Latronico MV, Napoli C, Sadoshima J, Croce CM, Ross J Jr (2002) Akt induces enhanced myocardial ­contractility and cell size in vivo in transgenic mice. Proc Natl Acad Sci USA 99(19):12333–12338. doi:10.1073/pnas.172376399

    Article  PubMed  CAS  Google Scholar 

  109. Koitabashi N, Aiba T, Hesketh GG, Rowell J, Zhang M, Takimoto E, Tomaselli GF, Kass DA (2010) Cyclic GMP/PKG-dependent inhibition of TRPC6 channel activity and expression negatively regulates cardiomyocyte NFAT activation Novel mechanism of cardiac stress modulation by PDE5 inhibition. J Mol Cell Cardiol 48(4):713–724. doi:10.1016/j.yjmcc.2009.11.015

    Article  PubMed  CAS  Google Scholar 

  110. Perez NG, Piaggio MR, Ennis IL, Garciarena CD, Morales C, Escudero EM, Cingolani OH, Chiappe de Cingolani G, Yang XP, Cingolani HE (2007) Phosphodiesterase 5A inhibition induces Na+/H+ exchanger blockade and protection against myocardial infarction. Hypertension 49(5):1095–1103. doi:10.1161/HYPERTENSIONAHA.107.087759

    Article  PubMed  CAS  Google Scholar 

  111. Yeves AM, Garciarena CD, Nolly MB, Chiappe de Cingolani GE, Cingolani HE, Ennis IL (2010) Decreased activity of the Na+/H+ exchanger by phosphodiesterase 5A inhibition is attributed to an increase in protein phosphatase activity. Hypertension 56(4):690–695. doi:10.1161/HYPERTENSIONAHA.110.151324

    Article  PubMed  CAS  Google Scholar 

  112. Wollert KC, Fiedler B, Gambaryan S, Smolenski A, Heineke J, Butt E, Trautwein C, Lohmann SM, Drexler H (2002) Gene transfer of cGMP-dependent protein kinase I enhances the antihypertrophic effects of nitric oxide in cardiomyocytes. Hypertension 39(1):87–92

    Article  PubMed  CAS  Google Scholar 

  113. Fiedler B, Lohmann SM, Smolenski A, Linnemuller S, Pieske B, Schroder F, Molkentin JD, Drexler H, Wollert KC (2002) Inhibition of calcineurin-NFAT hypertrophy signaling by cGMP-dependent protein kinase type I in cardiac myocytes. Proc Natl Acad Sci USA 99(17):11363–11368

    Article  PubMed  CAS  Google Scholar 

  114. Hsu S, Nagayama T, Koitabashi N, Zhang M, Zhou L, Bedja D, Gabrielson KL, Molkentin JD, Kass DA, Takimoto E (2009) Phosphodiesterase 5 inhibition blocks pressure overload-induced cardiac hypertrophy independent of the calcineurin pathway. Cardiovasc Res 81(2):301–309. doi:10.1093/cvr/cvn324

    Article  PubMed  CAS  Google Scholar 

  115. Das A, Xi L, Kukreja RC (2008) Protein kinase G-dependent cardioprotective mechanism of phosphodiesterase-5 inhibition involves phosphorylation of ERK and GSK3beta. J Biol Chem 283(43):29572–29585. doi:10.1074/jbc.M801547200

    Article  PubMed  CAS  Google Scholar 

  116. Takimoto E, Koitabashi N, Hsu S, Ketner EA, Zhang M, Nagayama T, Bedja D, Gabrielson KL, Blanton R, Siderovski DP, Mendelsohn ME, Kass DA (2009) Regulator of G protein signaling 2 mediates cardiac compensation to pressure overload and antihypertrophic effects of PDE5 inhibition in mice. J Clin Invest 119(2):408–420. doi:10.1172/JCI35620

    PubMed  CAS  Google Scholar 

  117. Klaiber M, Kruse M, Volker K, Schroter J, Feil R, Freichel M, Gerling A, Feil S, Dietrich A, Londono JE, Baba HA, Abramowitz J, Birnbaumer L, Penninger JM, Pongs O, Kuhn M (2010) Novel insights into the mechanisms mediating the local antihypertrophic effects of cardiac atrial natriuretic peptide: role of cGMP-dependent protein kinase and RGS2. Basic Res Cardiol 105(5):583–595. doi:10.1007/s00395-010-0098-z

    Article  PubMed  CAS  Google Scholar 

  118. Garcia-Dorado D, Agullo L, Sartorio CL, Ruiz-Meana M (2009) Myocardial protection against reperfusion injury: the cGMP pathway. Thromb Haemost 101(4):635–642

    PubMed  CAS  Google Scholar 

  119. Costa AD, Pierre SV, Cohen MV, Downey JM, Garlid KD (2008) cGMP signalling in pre- and post-conditioning: the role of mitochondria. Cardiovasc Res 77(2):344–352. doi:10.1093/cvr/cvm050

    Article  PubMed  CAS  Google Scholar 

  120. Gorbe A, Giricz Z, Szunyog A, Csont T, Burley DS, Baxter GF, Ferdinandy P (2010) Role of cGMP-PKG signaling in the protection of neonatal rat cardiac myocytes subjected to simulated ischemia/reoxygenation. Basic Res Cardiol 105(5):643–650. doi:10.1007/s00395-010-0097-0

    Article  PubMed  CAS  Google Scholar 

  121. Fiedler B, Feil R, Hofmann F, Willenbockel C, Drexler H, Smolenski A, Lohmann SM, Wollert KC (2006) cGMP-dependent protein kinase type I inhibits TAB1-p38 mitogen-activated protein kinase apoptosis signaling in cardiac myocytes. J Biol Chem 281(43):32831–32840. doi:10.1074/jbc.M603416200

    Article  PubMed  CAS  Google Scholar 

  122. Costa AD, Garlid KD, West IC, Lincoln TM, Downey JM, Cohen MV, Critz SD (2005) Protein kinase G transmits the cardioprotective signal from cytosol to mitochondria. Circ Res 97(4):329–336. doi:10.1161/01.RES.0000178451.08719.5b

    Article  PubMed  CAS  Google Scholar 

  123. Jang Y, Wang H, Xi J, Mueller RA, Norfleet EA, Xu Z (2007) NO mobilizes intracellular Zn2+ via cGMP/PKG signaling pathway and prevents mitochondrial oxidant damage in cardiomyocytes. Cardiovasc Res 75(2):­426–433. doi:10.1016/j.cardiores.2007.05.015

    Article  PubMed  CAS  Google Scholar 

  124. Li P, Wang D, Lucas J, Oparil S, Xing D, Cao X, Novak L, Renfrow MB, Chen YF (2008) Atrial natriuretic peptide inhibits transforming growth factor beta-induced Smad signaling and myofibroblast transformation in mouse cardiac fibroblasts. Circ Res 102(2):185–192. doi:10.1161/CIRCRESAHA.107.157677

    Article  PubMed  CAS  Google Scholar 

  125. Murthy KS (2006) Signaling for contraction and relaxation in smooth muscle of the gut. Annu Rev Physiol 68:345–374. doi:10.1146/annurev.physiol.68.040504.094707

    Article  PubMed  CAS  Google Scholar 

  126. Frei E, Huster M, Smital P, Schlossmann J, Hofmann F, Wegener JW (2009) Calcium-dependent and calcium-independent inhibition of contraction by cGMP/cGKI in intestinal smooth muscle. Am J Physiol Gastrointest Liver Physiol 297(4):G834–G839. doi:10.1152/ajpgi.00095.2009

    Article  PubMed  CAS  Google Scholar 

  127. Koeppen M, Feil R, Siegl D, Feil S, Hofmann F, Pohl U, de Wit C (2004) cGMP-dependent protein kinase mediates NO- but not acetylcholine-induced dilations in resistance vessels in vivo. Hypertension 44(6):952–955

    Article  PubMed  CAS  Google Scholar 

  128. Pfeifer A, Klatt P, Massberg S, Ny L, Sausbier M, Hirneiss C, Wang GX, Korth M, Aszodi A, Andersson KE, Krombach F, Mayerhofer A, Ruth P, Fassler R, Hofmann F (1998) Defective smooth muscle regulation in cGMP kinase I-deficient mice. EMBO J 17(11):3045–3051

    Article  PubMed  CAS  Google Scholar 

  129. Sausbier M, Schubert R, Voigt V, Hirneiss C, Pfeifer A, Korth M, Kleppisch T, Ruth P, Hofmann F (2000) Mechanisms of NO/cGMP-dependent vasorelaxation. Circ Res 87(9):825–830

    Article  PubMed  CAS  Google Scholar 

  130. Weber S, Bernhard D, Lukowski R, Weinmeister P, Worner R, Wegener JW, Valtcheva N, Feil S, Schlossmann J, Hofmann F, Feil R (2007) Rescue of cGMP kinase I knockout mice by smooth muscle specific expression of either isozyme. Circ Res 101(11):1096–1103

    Article  PubMed  CAS  Google Scholar 

  131. Geiselhöringer A, Werner M, Sigl K, Smital P, Worner R, Acheo L, Stieber J, Weinmeister P, Feil R, Feil S, Wegener J, Hofmann F, Schlossmann J (2004) IRAG is essential for relaxation of receptor-triggered smooth muscle contraction by cGMP kinase. EMBO J 23(21):4222–4231

    Article  PubMed  CAS  Google Scholar 

  132. Hofmann F, Ammendola A, Schlossmann J (2000) Rising behind NO: cGMP-dependent protein kinases. J Cell Sci 113(Pt 10):1671–1676

    PubMed  CAS  Google Scholar 

  133. Feil R, Gappa N, Rutz M, Schlossmann J, Rose CR, Konnerth A, Brummer S, Kuhbandner S, Hofmann F (2002) Functional reconstitution of vascular smooth muscle cells with cGMP-dependent protein kinase I isoforms. Circ Res 90(10):1080–1086

    Article  PubMed  CAS  Google Scholar 

  134. Geiselhöringer A, Gaisa M, Hofmann F, Schlossmann J (2004) Distribution of IRAG and cGKI-isoforms in murine tissues. FEBS Lett 575(1–3):19–22

    Article  PubMed  CAS  Google Scholar 

  135. Wolfe L, Corbin JD, Francis SH (1989) Characterization of a novel isozyme of ­cGMP-dependent protein kinase from bovine aorta. J Biol Chem 264(13):7734–7741

    PubMed  CAS  Google Scholar 

  136. Morgado M, Cairrao E, Santos-Silva AJ, Verde I (2012) Cyclic nucleotide-dependent relaxation pathways in vascular smooth muscle. Cell Mol Life Sci 69(2):247–266. doi:10.1007/s00018-011-0815-2

    Article  PubMed  CAS  Google Scholar 

  137. Vaandrager AB, de Jonge HR (1996) Signalling by cGMP-dependent protein kinases. Mol Cell Biochem 157(1–2):23–30

    PubMed  CAS  Google Scholar 

  138. Tanaka Y, Tang G, Takizawa K, Otsuka K, Eghbali M, Song M, Nishimaru K, Shigenobu K, Koike K, Stefani E, Toro L (2006) Kv channels contribute to nitric oxide- and atrial natriuretic peptide-induced relaxation of a rat conduit artery. J Pharmacol Exp Ther 317(1):341–354. doi:10.1124/jpet.105.096115

    Article  PubMed  CAS  Google Scholar 

  139. Rapoport RM (1986) Cyclic guanosine monophosphate inhibition of contraction may be mediated through inhibition of phosphatidylinositol hydrolysis in rat aorta. Circ Res 58(3):407–410

    Article  PubMed  CAS  Google Scholar 

  140. Xia C, Bao Z, Yue C, Sanborn BM, Liu M (2001) Phosphorylation and regulation of G-protein-activated phospholipase C-beta 3 by cGMP-dependent protein kinases. J Biol Chem 276(23):19770–19777

    Article  PubMed  CAS  Google Scholar 

  141. Hirata M, Kohse KP, Chang CH, Ikebe T, Murad F (1990) Mechanism of cyclic GMP inhibition of inositol phosphate formation in rat aorta segments and cultured bovine aortic smooth muscle cells. J Biol Chem 265(3):1268–1273

    PubMed  CAS  Google Scholar 

  142. Hepler JR (1999) Emerging roles for RGS proteins in cell signalling. Trends Pharmacol Sci 20(9):376–382

    Article  PubMed  CAS  Google Scholar 

  143. Tang KM, Wang GR, Lu P, Karas RH, Aronovitz M, Heximer SP, Kaltenbronn KM, Blumer KJ, Siderovski DP, Zhu Y, Mendelsohn ME (2003) Regulator of G-protein signaling-2 mediates vascular smooth muscle relaxation and blood pressure. Nat Med 9(12):1506–1512

    Article  PubMed  CAS  Google Scholar 

  144. Huang J, Zhou H, Mahavadi S, Sriwai W, Murthy KS (2007) Inhibition of Galphaq-dependent PLC-beta1 activity by PKG and PKA is mediated by phosphorylation of RGS4 and GRK2. Am J Physiol Cell Physiol 292(1):C200–C208. doi:10.1152/ajpcell.00103.2006

    Article  PubMed  CAS  Google Scholar 

  145. Pedram A, Razandi M, Kehrl J, Levin ER (2000) Natriuretic peptides inhibit G protein activation. Mediation through cross-talk between cyclic GMP-dependent protein kinase and regulators of G protein-signaling proteins. J Biol Chem 275(10):7365–7372

    Article  PubMed  CAS  Google Scholar 

  146. Sun X, Kaltenbronn KM, Steinberg TH, Blumer KJ (2005) RGS2 is a mediator of nitric oxide action on blood pressure and vasoconstrictor signaling. Mol Pharmacol 67(3):631–639

    Article  PubMed  CAS  Google Scholar 

  147. Wang GR, Zhu Y, Halushka PV, Lincoln TM, Mendelsohn ME (1998) Mechanism of platelet inhibition by nitric oxide: in vivo phosphorylation of thromboxane receptor by cyclic GMP-dependent protein kinase. Proc Natl Acad Sci USA 95(9):4888–4893

    Article  PubMed  CAS  Google Scholar 

  148. Klages B, Brandt U, Simon MI, Schultz G, Offermanns S (1999) Activation of G12/G13 results in shape change and Rho/Rho-kinase-mediated myosin light chain phosphorylation in mouse platelets. J Cell Biol 144(4):745–754

    Article  PubMed  CAS  Google Scholar 

  149. Somlyo AP, Somlyo AV (2003) Ca2+ sensitivity of smooth muscle and nonmuscle myosin II: modulated by G proteins, kinases, and myosin phosphatase. Physiol Rev 83(4):1325–1358

    PubMed  CAS  Google Scholar 

  150. Komalavilas P, Lincoln TM (1994) Phosphorylation of the inositol 1,4,5-trisphosphate receptor by cyclic GMP-dependent protein kinase. J Biol Chem 269(12):8701–8707

    PubMed  CAS  Google Scholar 

  151. Komalavilas P, Lincoln TM (1996) Phosphorylation of the inositol 1,4,5-trisphosphate receptor. Cyclic GMP-dependent protein kinase mediates cAMP and cGMP dependent phosphorylation in the intact rat aorta. J Biol Chem 271(36):21933–21938

    Article  PubMed  CAS  Google Scholar 

  152. Schlossmann J, Ammendola A, Ashman K, Zong X, Huber A, Neubauer G, Wang GX, Allescher HD, Korth M, Wilm M, Hofmann F, Ruth P (2000) Regulation of intracellular calcium by a signalling complex of IRAG, IP3 receptor and cGMP kinase Ibeta. Nature 404(6774):197–201

    Article  PubMed  CAS  Google Scholar 

  153. Ammendola A, Geiselhoringer A, Hofmann F, Schlossmann J (2001) Molecular determinants of the interaction between the inositol 1,4,5-trisphosphate receptor-associated cGMP kinase substrate (IRAG) and cGMP kinase Ibeta. J Biol Chem 276(26):24153–24159

    Article  PubMed  CAS  Google Scholar 

  154. Desch M, Sigl K, Hieke B, Salb K, Kees F, Bernhard D, Jochim A, Spiessberger B, Hocherl K, Feil R, Feil S, Lukowski R, Wegener JW, Hofmann F, Schlossmann J (2010) IRAG determines nitric oxide- and atrial natriuretic peptide-mediated smooth muscle relaxation. Cardiovasc Res 86(3):496–505. doi:10.1093/cvr/cvq008

    Article  PubMed  CAS  Google Scholar 

  155. Welling A, Ludwig A, Zimmer S, Klugbauer N, Flockerzi V, Hofmann F (1997) Alternatively spliced IS6 segments of the alpha 1C gene determine the tissue-specific dihydropyridine sensitivity of cardiac and ­vascular smooth muscle l-type Ca2+ channels. Circ Res 81(4):526–532

    Article  PubMed  CAS  Google Scholar 

  156. Lorenz JN, Bielefeld DR, Sperelakis N (1994) Regulation of calcium channel current in A7r5 vascular smooth muscle cells by cyclic nucleotides. Am J Physiol 266(6 Pt 1):C1656–C1663

    PubMed  CAS  Google Scholar 

  157. Ruiz-Velasco V, Zhong J, Hume JR, Keef KD (1998) Modulation of Ca2+ channels by cyclic nucleotide cross activation of opposing protein kinases in rabbit portal vein. Circ Res 82(5):557–565

    Article  PubMed  CAS  Google Scholar 

  158. Chen J, Crossland RF, Noorani MM, Marrelli SP (2009) Inhibition of TRPC1/TRPC3 by PKG contributes to NO-mediated vasorelaxation. Am J Physiol Heart Circ Physiol 297(1):H417–H424. doi:10.1152/ajpheart.01130.2008

    Article  PubMed  CAS  Google Scholar 

  159. Inoue R, Okada T, Onoue H, Hara Y, Shimizu S, Naitoh S, Ito Y, Mori Y (2001) The transient receptor potential protein homologue TRP6 is the essential component of vascular alpha(1)-adrenoceptor-activated Ca(2+)-permeable cation channel. Circ Res 88(3):325–332

    Article  PubMed  CAS  Google Scholar 

  160. Koller A, Schlossmann J, Ashman K, Uttenweiler-Joseph S, Ruth P, Hofmann F (2003) Association of phospholamban with a cGMP kinase signaling complex. Biochem Biophys Res Commun 300(1):155–160

    Article  PubMed  CAS  Google Scholar 

  161. Raeymaekers L, Hofmann F, Casteels R (1988) Cyclic GMP-dependent protein kinase phosphorylates phospholamban in isolated sarcoplasmic reticulum from cardiac and smooth muscle. Biochem J 252(1):269–273

    PubMed  CAS  Google Scholar 

  162. Lalli MJ, Shimizu S, Sutliff RL, Kranias EG, Paul RJ (1999) [Ca2+]i homeostasis and cyclic nucleotide relaxation in aorta of phospholamban-deficient mice. Am J Physiol 277(3 Pt 2):H963–H970

    PubMed  CAS  Google Scholar 

  163. Cornwell TL, Pryzwansky KB, Wyatt TA, Lincoln TM (1991) Regulation of sarcoplasmic reticulum protein phosphorylation by localized cyclic GMP-dependent protein kinase in vascular smooth muscle cells. Mol Pharmacol 40(6):923–931

    PubMed  CAS  Google Scholar 

  164. Kobayashi S, Kanaide H, Nakamura M (1985) Cytosolic-free calcium transients in cultured vascular smooth muscle cells: microfluorometric measurements. Science 229(4713):553–556

    Article  PubMed  CAS  Google Scholar 

  165. Rashatwar SS, Cornwell TL, Lincoln TM (1987) Effects of 8-bromo-cGMP on Ca2+ levels in vascular smooth muscle cells: possible regulation of Ca2+-ATPase by cGMP-dependent protein kinase. Proc Natl Acad Sci USA 84(16):5685–5689

    Article  PubMed  CAS  Google Scholar 

  166. Vrolix M, Raeymaekers L, Wuytack F, Hofmann F, Casteels R (1988) Cyclic GMP-dependent protein kinase stimulates the plasmalemmal Ca2+ pump of smooth muscle via phosphorylation of phosphatidylinositol. Biochem J 255(3):855–863

    PubMed  CAS  Google Scholar 

  167. Furukawa K, Nakamura H (1987) Cyclic GMP regulation of the plasma membrane (Ca2+−Mg2+)ATPase in vascular smooth muscle. J Biochem 101(1):287–290

    PubMed  CAS  Google Scholar 

  168. Furukawa K, Ohshima N, Tawada-Iwata Y, Shigekawa M (1991) Cyclic GMP stimulates Na+/Ca2+ exchange in vascular smooth muscle cells in primary culture. J Biol Chem 266(19):12337–12341

    PubMed  CAS  Google Scholar 

  169. Taniguchi J, Furukawa KI, Shigekawa M (1993) Maxi K+ channels are stimulated by cyclic guanosine monophosphate-dependent protein kinase in canine coronary artery smooth muscle cells. Pflugers Arch 423(3–4):167–172

    Article  PubMed  CAS  Google Scholar 

  170. Robertson BE, Schubert R, Hescheler J, Nelson MT (1993) cGMP-dependent protein kinase activates Ca-activated K channels in cerebral artery smooth muscle cells. Am J Physiol 265(1 Pt 1):C299–C303

    PubMed  CAS  Google Scholar 

  171. Alioua A, Tanaka Y, Wallner M, Hofmann F, Ruth P, Meera P, Toro L (1998) The large conductance, voltage-dependent, and calcium-sensitive K+ channel, Hslo, is a target of cGMP-dependent protein kinase phosphorylation in vivo. J Biol Chem 273(49):32950–32956

    Article  PubMed  CAS  Google Scholar 

  172. Bolotina VM, Najibi S, Palacino JJ, Pagano PJ, Cohen RA (1994) Nitric oxide directly activates calcium-dependent potassium channels in vascular smooth muscle. Nature 368(6474):850–853. doi:10.1038/368850a0

    Article  PubMed  CAS  Google Scholar 

  173. Fukao M, Mason HS, Britton FC, Kenyon JL, Horowitz B, Keef KD (1999) Cyclic GMP-dependent protein kinase activates cloned BKCa channels expressed in mammalian cells by direct phosphorylation at serine 1072. J Biol Chem 274(16):10927–10935

    Article  PubMed  CAS  Google Scholar 

  174. Zhou XB, Ruth P, Schlossmann J, Hofmann F, Korth M (1996) Protein phosphatase 2A is essential for the activation of Ca2+-activated K+ currents by cGMP-dependent protein kinase in tracheal smooth muscle and Chinese hamster ovary cells. J Biol Chem 271(33):19760–19767

    Article  PubMed  CAS  Google Scholar 

  175. White RE, Lee AB, Shcherbatko AD, Lincoln TM, Schonbrunn A, Armstrong DL (1993) Potassium channel stimulation by natriuretic peptides through cGMP-dependent dephosphorylation. Nature 361(6409):263–266

    Article  PubMed  CAS  Google Scholar 

  176. Surks HK, Mochizuki N, Kasai Y, Georgescu SP, Tang KM, Ito M, Lincoln TM, Mendelsohn ME (1999) Regulation of myosin phosphatase by a specific interaction with cGMP-dependent protein kinase Ialpha. Science 286(5444):1583–1587

    Article  PubMed  CAS  Google Scholar 

  177. Wooldridge AA, MacDonald JA, Erdodi F, Ma C, Borman MA, Hartshorne DJ, Haystead TA (2004) Smooth muscle phosphatase is regulated in vivo by exclusion of phosphorylation of threonine 696 of MYPT1 by phosphorylation of Serine 695 in response to cyclic nucleotides. J Biol Chem 279(33):34496–34504

    Article  PubMed  CAS  Google Scholar 

  178. Lee MR, Li L, Kitazawa T (1997) Cyclic GMP causes Ca2+ desensitization in vascular smooth muscle by activating the myosin light chain phosphatase. J Biol Chem 272(8):5063–5068

    Article  PubMed  CAS  Google Scholar 

  179. Nakamura K, Koga Y, Sakai H, Homma K, Ikebe M (2007) cGMP-dependent relaxation of smooth muscle is coupled with the change in the phosphorylation of myosin phosphatase. Circ Res 101(7):712–722. doi:10.1161/CIRCRESAHA.107.153981

    Article  PubMed  CAS  Google Scholar 

  180. Somlyo AV (2007) Cyclic GMP regulation of myosin phosphatase: a new piece for the puzzle? Circ Res 101(7):645–647. doi:10.1161/CIRCRESAHA.107.161893

    Article  PubMed  CAS  Google Scholar 

  181. Khromov AS, Wang H, Choudhury N, McDuffie M, Herring BP, Nakamoto R, Owens GK, Somlyo AP, Somlyo AV (2006) Smooth muscle of telokin-deficient mice exhibits increased sensitivity to Ca2+ and decreased cGMP-induced relaxation. Proc Natl Acad Sci USA 103(7):2440–2445. doi:10.1073/pnas.0508566103

    Article  PubMed  CAS  Google Scholar 

  182. Borman MA, MacDonald JA, Haystead TA (2004) Modulation of smooth muscle contractility by CHASM, a novel member of the smoothelin family of proteins. FEBS Lett 573(1–3):207–213. doi:10.1016/j.febslet.2004.08.002

    Article  PubMed  CAS  Google Scholar 

  183. Sauzeau V, Le Jeune H, Cario-Toumaniantz C, Smolenski A, Lohmann SM, Bertoglio J, Chardin P, Pacaud P, Loirand G (2000) Cyclic GMP-dependent protein kinase signaling pathway inhibits RhoA-induced Ca2+ ­sensitization of contraction in vascular smooth muscle. J Biol Chem 275(28):21722–21729

    Article  PubMed  CAS  Google Scholar 

  184. Loirand G, Guerin P, Pacaud P (2006) Rho kinases in cardiovascular physiology and pathophysiology. Circ Res 98(3):322–334. doi:10.1161/01.RES.0000201960.04223.3c

    Article  PubMed  CAS  Google Scholar 

  185. Sakurada S, Takuwa N, Sugimoto N, Wang Y, Seto M, Sasaki Y, Takuwa Y (2003) Ca2+-dependent activation of Rho and Rho kinase in membrane depolarization-induced and receptor stimulation-induced vascular smooth ­muscle contraction. Circ Res 93(6):548–556. doi:10.1161/01.RES.0000090998.08629.60

    Article  PubMed  CAS  Google Scholar 

  186. Bonnevier J, Arner A (2004) Actions downstream of cyclic GMP/protein kinase G can reverse protein kinase C-mediated phosphorylation of CPI-17 and Ca(2+) sensitization in smooth muscle. J Biol Chem 279(28):28998–29003

    Article  PubMed  CAS  Google Scholar 

  187. Woodrum DA, Brophy CM, Wingard CJ, Beall A, Rasmussen H (1999) Phosphorylation events associated with cyclic nucleotide-dependent inhibition of smooth muscle contraction. Am J Physiol 277(3 Pt 2):H931–H939

    PubMed  CAS  Google Scholar 

  188. Rembold CM, Foster DB, Strauss JD, Wingard CJ, Eyk JE (2000) cGMP-mediated phosphorylation of heat shock protein 20 may cause smooth muscle relaxation without myosin light chain dephosphorylation in swine carotid artery. J Physiol 524(Pt 3):865–878

    Article  PubMed  CAS  Google Scholar 

  189. Woodrum D, Pipkin W, Tessier D, Komalavilas P, Brophy CM (2003) Phosphorylation of the heat shock-related protein, HSP20, mediates cyclic nucleotide-dependent relaxation. J Vasc Surg 37(4):874–881. doi:10.1067/mva.2003.153

    Article  PubMed  Google Scholar 

  190. Essin K, Welling A, Hofmann F, Luft FC, Gollasch M, Moosmang S (2007) Indirect coupling between Cav1.2 channels and ryanodine receptors to generate Ca2+ sparks in murine arterial smooth muscle cells. J Physiol 584(Pt 1):205–219

    Article  PubMed  CAS  Google Scholar 

  191. Moosmang S, Schulla V, Welling A, Feil R, Feil S, Wegener JW, Hofmann F, Klugbauer N (2003) Dominant role of smooth muscle l-type calcium channel Cav1.2 for blood pressure regulation. EMBO J 22(22):6027–6034

    Article  PubMed  CAS  Google Scholar 

  192. Wegener JW, Schulla V, Lee TS, Koller A, Feil S, Feil R, Kleppisch T, Klugbauer N, Moosmang S, Welling A, Hofmann F (2004) An essential role of Cav1.2  l-type calcium channel for urinary bladder function. FASEB J 18(10):1159–1161

    PubMed  CAS  Google Scholar 

  193. Huang PL, Huang Z, Mashimo H, Bloch KD, Moskowitz MA, Bevan JA, Fishman MC (1995) Hypertension in mice lacking the gene for endothelial nitric oxide synthase. Nature 377(6546):239–242

    Article  PubMed  CAS  Google Scholar 

  194. Kuhn M (2005) Cardiac and intestinal natriuretic peptides: insights from genetically modified mice. Peptides 26(6):1078–1085

    Article  PubMed  CAS  Google Scholar 

  195. Sausbier M, Arntz C, Bucurenciu I, Zhao H, Zhou XB, Sausbier U, Feil S, Kamm S, Essin K, Sailer CA, Abdullah U, Krippeit-Drews P, Feil R, Hofmann F, Knaus HG, Kenyon C, Shipston MJ, Storm JF, Neuhuber W, Korth M, Schubert R, Gollasch M, Ruth P (2005) Elevated blood pressure linked to primary hyperaldosteronism and impaired vasodilation in BK channel-deficient mice. Circulation 112(1):60–68. doi:10.1161/01.CIR.0000156448.74296.FE

    Article  PubMed  CAS  Google Scholar 

  196. Faraci FM, Sigmund CD (1999) Vascular biology in genetically altered mice: smaller vessels, bigger insight. Circ Res 85(12):1214–1225

    Article  PubMed  CAS  Google Scholar 

  197. Murata T, Ushikubi F, Matsuoka T, Hirata M, Yamasaki A, Sugimoto Y, Ichikawa A, Aze Y, Tanaka T, Yoshida N, Ueno A, Oh-ishi S, Narumiya S (1997) Altered pain perception and inflammatory response in mice lacking prostacyclin receptor. Nature 388(6643):678–682. doi:10.1038/41780

    Article  PubMed  CAS  Google Scholar 

  198. Meng W, Ayata C, Waeber C, Huang PL, Moskowitz MA (1998) Neuronal NOS-cGMP-dependent ACh-induced relaxation in pial arterioles of endothelial NOS knockout mice. Am J Physiol 274(2 Pt 2):H411–H415

    PubMed  CAS  Google Scholar 

  199. Friebe A, Mergia E, Dangel O, Lange A, Koesling D (2007) Fatal gastrointestinal obstruction and hypertension in mice lacking nitric oxide-sensitive guanylyl cyclase. Proc Natl Acad Sci USA 104(18):7699–7704

    Article  PubMed  CAS  Google Scholar 

  200. Landgraf W, Regulla S, Meyer HE, Hofmann F (1991) Oxidation of cysteines activates cGMP-dependent protein kinase. J Biol Chem 266(25):16305–16311

    PubMed  CAS  Google Scholar 

  201. Osborne BW, Wu J, McFarland CJ, Nickl CK, Sankaran B, Casteel DE, Woods VL Jr, Kornev AP, Taylor SS, Dostmann WR (2011) Crystal structure of cGMP-dependent protein kinase reveals novel site of interchain communication. Structure 19(9):1317–1327

    Article  PubMed  CAS  Google Scholar 

  202. Burgoyne JR, Madhani M, Cuello F, Charles RL, Brennan JP, Schroder E, Browning DD, Eaton P (2007) Cysteine redox sensor in PKGIa enables oxidant-induced activation. Science 317(5843):1393–1397

    Article  PubMed  CAS  Google Scholar 

  203. Prysyazhna O, Rudyk O, Eaton P (2012) Single atom substitution in mouse protein kinase G eliminates oxidant sensing to cause hypertension. Nat Med 18(2):286–290

    Article  PubMed  CAS  Google Scholar 

  204. Ozaki M, Kawashima S, Yamashita T, Hirase T, Namiki M, Inoue N, Hirata K, Yasui H, Sakurai H, Yoshida Y, Masada M, Yokoyama M (2002) Overexpression of endothelial nitric oxide synthase accelerates atherosclerotic lesion formation in apoE-deficient mice. J Clin Invest 110(3):331–340

    PubMed  CAS  Google Scholar 

  205. Kuhlencordt PJ, Chen J, Han F, Astern J, Huang PL (2001) Genetic deficiency of inducible nitric oxide synthase reduces ­atherosclerosis and lowers plasma lipid peroxides in apolipoprotein E-knockout mice. Circulation 103(25):3099–3104

    Article  PubMed  CAS  Google Scholar 

  206. Chyu KY, Dimayuga P, Zhu J, Nilsson J, Kaul S, Shah PK, Cercek B (1999) Decreased neointimal thickening after arterial wall injury in inducible nitric oxide synthase knockout mice. Circ Res 85(12):1192–1198

    Article  PubMed  CAS  Google Scholar 

  207. Tolbert T, Thompson JA, Bouchard P, Oparil S (2001) Estrogen-induced vasoprotection is independent of inducible nitric oxide synthase expression: evidence from the mouse carotid artery ligation model. Circulation 104(22):2740–2745

    Article  PubMed  CAS  Google Scholar 

  208. Detmers PA, Hernandez M, Mudgett J, Hassing H, Burton C, Mundt S, Chun S, Fletcher D, Card DJ, Lisnock J, Weikel R, Bergstrom JD, Shevell DE, Hermanowski-Vosatka A, Sparrow CP, Chao YS, Rader DJ, Wright SD, Pure E (2000) Deficiency in inducible nitric oxide synthase results in reduced atherosclerosis in apolipoprotein E-deficient mice. J Immunol 165(6):3430–3435

    PubMed  CAS  Google Scholar 

  209. Sennlaub F, Courtois Y, Goureau O (2001) Inducible nitric oxide synthase mediates the change from retinal to vitreal neovascularization in ischemic retinopathy. J Clin Invest 107(6):717–725

    Article  PubMed  CAS  Google Scholar 

  210. Knowles JW, Reddick RL, Jennette JC, Shesely EG, Smithies O, Maeda N (2000) Enhanced atherosclerosis and kidney dysfunction in eNOS(−/−)Apoe(−/−) mice are ameliorated by enalapril treatment. J Clin Invest 105(4):451–458

    Article  PubMed  CAS  Google Scholar 

  211. Kuhlencordt PJ, Gyurko R, Han F, Scherrer-Crosbie M, Aretz TH, Hajjar R, Picard MH, Huang PL (2001) Accelerated atherosclerosis, aortic aneurysm formation, and ischemic heart disease in apolipoprotein E/endothelial nitric oxide synthase double-knockout mice. Circulation 104(4):448–454

    Article  PubMed  CAS  Google Scholar 

  212. Moroi M, Zhang L, Yasuda T, Virmani R, Gold HK, Fishman MC, Huang PL (1998) Interaction of genetic deficiency of endothelial nitric oxide, gender, and pregnancy in vascular response to injury in mice. J Clin Invest 101(6):1225–1232

    Article  PubMed  CAS  Google Scholar 

  213. Rudic RD, Shesely EG, Maeda N, Smithies O, Segal SS, Sessa WC (1998) Direct evidence for the importance of endothelium-derived nitric oxide in vascular remodeling. J Clin Invest 101(4):731–736

    Article  PubMed  CAS  Google Scholar 

  214. Chen J, Kuhlencordt PJ, Astern J, Gyurko R, Huang PL (2001) Hypertension does not account for the accelerated atherosclerosis and development of aneurysms in male apolipoprotein e/endothelial nitric oxide synthase double knockout mice. Circulation 104(20):2391–2394

    Article  PubMed  CAS  Google Scholar 

  215. Koglin J, Glysing-Jensen T, Mudgett JS, Russell ME (1998) Exacerbated transplant arteriosclerosis in inducible nitric oxide- deficient mice. Circulation 97(20):2059–2065

    Article  PubMed  CAS  Google Scholar 

  216. Lablanche JM, Grollier G, Lusson JR, Bassand JP, Drobinski G, Bertrand B, Battaglia S, Desveaux B, Juilliere Y, Juliard JM, Metzger JP, Coste P, Quiret JC, Dubois-Rande JL, Crochet PD, Letac B, Boschat J, Virot P, Finet G, Le Breton H, Livarek B, Leclercq F, Beard T, Giraud T, Bertrand ME et al (1997) Effect of the direct nitric oxide donors linsidomine and molsidomine on angiographic restenosis after coronary balloon angioplasty. The ACCORD study. angioplastic coronaire corvasal diltiazem. Circulation 95(1):83–89

    Article  PubMed  Google Scholar 

  217. Poon BY, Raharjo E, Patel KD, Tavener S, Kubes P (2003) Complexity of inducible nitric oxide synthase: cellular source determines benefit versus toxicity. Circulation 108(9):1107–1112

    Article  PubMed  CAS  Google Scholar 

  218. Berk BC (2001) Vascular smooth muscle growth: autocrine growth mechanisms. Physiol Rev 81(3):999–1030

    PubMed  CAS  Google Scholar 

  219. Dzau VJ, Braun-Dullaeus RC, Sedding DG (2002) Vascular proliferation and atherosclerosis: new perspectives and therapeutic strategies. Nat Med 8(11):1249–1256

    Article  PubMed  CAS  Google Scholar 

  220. Owens GK, Kumar MS, Wamhoff BR (2004) Molecular regulation of vascular smooth muscle cell differentiation in development and disease. Physiol Rev 84(3):767–801

    Article  PubMed  CAS  Google Scholar 

  221. Schwartz SM, deBlois D, O’Brien ER (1995) The intima. Soil for atherosclerosis and restenosis. Circ Res 77(3):445–465

    Article  PubMed  CAS  Google Scholar 

  222. Hofmann F, Feil R, Kleppisch T, Schlossmann J (2006) Function of cGMP-dependent protein kinases as revealed by gene deletion. Physiol Rev 86(1):1–23

    Article  PubMed  CAS  Google Scholar 

  223. Weinmeister P, Lukowski R, Linder S, Traidl-Hoffmann C, Hengst L, Hofmann F, Feil R (2008) Cyclic guanosine monophosphate-dependent protein kinase I promotes adhesion of primary vascular smooth muscle cells. Mol Biol Cell 19(10):4434–4441. doi:10.1091/mbc.E08-04-0370

    Article  PubMed  CAS  Google Scholar 

  224. Eigenthaler M, Lohmann SM, Walter U, Pilz RB (1999) Signal transduction by cGMP-dependent protein kinases and their emerging roles in the regulation of cell adhesion and gene expression. Rev Physiol Biochem Pharmacol 135:173–209

    Article  PubMed  CAS  Google Scholar 

  225. Lincoln TM, Dey N, Sellak H (2001) Invited review: cGMP-dependent protein kinase signaling mechanisms in smooth muscle: from the regulation of tone to gene expression. J Appl Physiol 91(3):1421–1430

    PubMed  CAS  Google Scholar 

  226. Pilz RB, Casteel DE (2003) Regulation of gene expression by cyclic GMP. Circ Res 93(11):1034–1046

    Article  PubMed  CAS  Google Scholar 

  227. Lincoln TM, Wu X, Sellak H, Dey N, Choi CS (2006) Regulation of vascular smooth muscle cell phenotype by cyclic GMP and cyclic GMP-dependent protein kinase. Front Biosci 11:356–367

    Article  PubMed  CAS  Google Scholar 

  228. Kawai-Kowase K, Owens GK (2007) Multiple repressor pathways contribute to phenotypic switching of vascular smooth muscle cells. Am J Physiol Cell Physiol 292(1):C59–C69

    Article  PubMed  CAS  Google Scholar 

  229. Cornwell TL, Arnold E, Boerth NJ, Lincoln TM (1994) Inhibition of smooth muscle cell growth by nitric oxide and activation of cAMP-dependent protein kinase by cGMP. Am J Physiol 267(5 Pt 1):C1405–C1413

    PubMed  CAS  Google Scholar 

  230. Boerth NJ, Dey NB, Cornwell TL, Lincoln TM (1997) Cyclic GMP-dependent protein kinase regulates vascular smooth muscle cell phenotype. J Vasc Res 34(4):245–259

    Article  PubMed  CAS  Google Scholar 

  231. Negash S, Narasimhan SR, Zhou W, Liu J, Wei FL, Tian J, Raj JU (2009) Role of cGMP-dependent protein kinase in regulation of pulmonary vascular smooth muscle cell adhesion and migration: effect of hypoxia. Am J Physiol Heart Circ Physiol 297(1):H304–H312. doi:10.1152/ajpheart.00077.2008

    Article  PubMed  CAS  Google Scholar 

  232. Pauly RR, Passaniti A, Bilato C, Monticone R, Cheng L, Papadopoulos N, Gluzband YA, Smith L, Weinstein C, Lakatta EG et al (1994) Migration of cultured vascular smooth muscle cells through a basement membrane barrier requires type IV collagenase activity and is inhibited by cellular differentiation. Circ Res 75(1):41–54

    Article  PubMed  CAS  Google Scholar 

  233. Bendeck MP, Irvin C, Reidy MA (1996) Inhibition of matrix metalloproteinase activity inhibits smooth muscle cell migration but not neointimal thickening after arterial injury. Circ Res 78(1):38–43

    Article  PubMed  CAS  Google Scholar 

  234. Dey NB, Lincoln TM (2012) Possible involvement of cyclic-GMP-dependent protein kinase on matrix metalloproteinase-2 expression in rat aortic smooth muscle cells. Mol Cell Biochem 368(1–2):27–35. doi:10.1007/s11010-012-1339-2

    Article  PubMed  CAS  Google Scholar 

  235. Liu N, Olson EN (2006) Coactivator control of cardiovascular growth and remodeling. Curr Opin Cell Biol 18(6):715–722

    Article  PubMed  CAS  Google Scholar 

  236. Huber A, Neuhuber WL, Klugbauer N, Ruth P, Allescher HD (2000) Cysteine-rich protein 2, a novel substrate for cGMP kinase I in enteric neurons and intestinal smooth muscle. J Biol Chem 275(8):5504–5511

    Article  PubMed  CAS  Google Scholar 

  237. Karim MA, Ohta K, Egashira M, Jinno Y, Niikawa N, Matsuda I, Indo Y (1996) Human ESP1/CRP2, a member of the LIM domain protein family: characterization of the cDNA and assignment of the gene locus to chromosome 14q32.3. Genomics 31(2):167–176

    Article  PubMed  CAS  Google Scholar 

  238. Okano I, Yamamoto T, Kaji A, Kimura T, Mizuno K, Nakamura T (1993) Cloning of CRP2, a novel member of the cysteine-rich protein family with two repeats of an unusual LIM/double zinc-finger motif. FEBS Lett 333(1–2):51–55

    Article  PubMed  CAS  Google Scholar 

  239. Zhang T, Zhuang S, Casteel DE, Looney DJ, Boss GR, Pilz RB (2007) A cysteine-rich LIM-only protein mediates regulation of smooth muscle-specific gene expression by cGMP-dependent protein kinase. J Biol Chem 282(46):33367–33380

    Article  PubMed  CAS  Google Scholar 

  240. Schmidtko A, Gao W, Sausbier M, Rauhmeier I, Sausbier U, Niederberger E, Scholich K, Huber A, Neuhuber W, Allescher HD, Hofmann F, Tegeder I, Ruth P, Geisslinger G (2008) Cysteine-rich protein 2, a novel downstream effector of cGMP/cGMP-dependent protein kinase I-mediated persistent inflammatory pain. J Neurosci 28(6):1320–1330. doi:10.1523/JNEUROSCI.5037-07.2008

    Article  PubMed  CAS  Google Scholar 

  241. Sinnaeve P, Chiche JD, Gillijns H, Van Pelt N, Wirthlin D, Van De Werf F, Collen D, Bloch KD, Janssens S (2002) Overexpression of a constitutively active protein kinase G mutant reduces neointima formation and in-stent restenosis. Circulation 105(24):2911–2916

    Article  PubMed  CAS  Google Scholar 

  242. Lukowski R, Weinmeister P, Bernhard D, Feil S, Gotthardt M, Herz J, Massberg S, Zernecke A, Weber C, Hofmann F, Feil R (2008) Role of smooth muscle cGMP/cGKI signaling in murine vascular restenosis. Arterioscler Thromb Vasc Biol 28(7):1244–1250. doi:10.1161/ATVBAHA.108.166405

    Article  PubMed  CAS  Google Scholar 

  243. Werner C, Raivich G, Cowen M, Strekalova T, Sillaber I, Buters JT, Spanagel R, Hofmann F (2004) Importance of NO/cGMP signalling via cGMP-dependent protein kinase II for controlling emotionality and neurobehavioural effects of alcohol. Eur J Neurosci 20(12):3498–3506

    Article  PubMed  Google Scholar 

  244. el-Husseini AE, Bladen C, Vincent SR (1995) Molecular characterization of a type II cyclic GMP-dependent protein kinase expressed in the rat brain. J Neurochem 64(6):2814–2817

    Article  PubMed  CAS  Google Scholar 

  245. Feil S, Zimmermann P, Knorn A, Brummer S, Schlossmann J, Hofmann F, Feil R (2005) Distribution of cGMP-dependent protein kinase type I and its isoforms in the mouse brain and retina. Neuroscience 135(3):863–868

    Article  PubMed  CAS  Google Scholar 

  246. Singh AK, Spiessberger B, Zheng W, Xiao F, Lukowski R, Wegener JW, Weinmeister P, Saur D, Klein S, Schemann M, Krueger D, Seidler U, Hofmann F (2012) Neuronal cGMP kinase I is essential for stimulation of duodenal bicarbonate secretion by luminal acid. FASEB J 26(4):1745–1754

    Article  PubMed  CAS  Google Scholar 

  247. Paul C, Schoberl F, Weinmeister P, Micale V, Wotjak CT, Hofmann F, Kleppisch T (2008) Signaling through cGMP-dependent protein kinase I in the amygdala is critical for auditory-cued fear memory and long-term potentiation. J Neurosci 28(52):14202–14212

    Article  PubMed  CAS  Google Scholar 

  248. Oster H, Werner C, Magnone MC, Mayser H, Feil R, Seeliger MW, Hofmann F, Albrecht U (2003) cGMP-dependent protein kinase II modulates mPer1 and mPer2 gene induction and influences phase shifts of the circadian clock. Curr Biol 13(9):725–733

    Article  PubMed  CAS  Google Scholar 

  249. Revermann M, Maronde E, Ruth P, Korf HW (2002) Protein kinase G I immunoreaction is colocalized with arginine-vasopressin immunoreaction in the rat suprachiasmatic nucleus. Neurosci Lett 334(2):119–122

    Article  PubMed  CAS  Google Scholar 

  250. Weber ET, Gannon RL, Rea MA (1995) cGMP-dependent protein kinase inhibitor blocks light-induced phase advances of circadian rhythms in vivo. Neurosci Lett 197(3):227–230

    Article  PubMed  CAS  Google Scholar 

  251. Mathur A, Golombek DA, Ralph MR (1996) cGMP-dependent protein kinase inhibitors block light-induced phase advances of circadian rhythms in vivo. Am J Physiol 270(5 Pt 2):R1031–R1036

    PubMed  CAS  Google Scholar 

  252. Tischkau SA, Mitchell JW, Pace LA, Barnes JW, Barnes JA, Gillette MU (2004) Protein kinase G type II is required for night-to-day progression of the mammalian circadian clock. Neuron 43(4):539–549

    Article  PubMed  CAS  Google Scholar 

  253. Langmesser S, Franken P, Feil S, Emmenegger Y, Albrecht U, Feil R (2009) cGMP-dependent protein kinase type I is implicated in the regulation of the timing and quality of sleep and wakefulness. PLoS One 4(1):e4238

    Article  PubMed  CAS  Google Scholar 

  254. Sold G, Hofmann F (1974) Evidence for a guanosine-3′:5′-monophosphate-binding protein from rat cerebellum. Eur J Biochem 44(1):143–149

    Article  PubMed  CAS  Google Scholar 

  255. Lohmann SM, Walter U, Miller PE, Greengard P, De Camilli P (1981) Immunohistochemical localization of cyclic GMP-dependent protein kinase in mammalian brain. Proc Natl Acad Sci USA 78(1):653–657

    Article  PubMed  CAS  Google Scholar 

  256. Li Z, Xi X, Gu M, Feil R, Ye RD, Eigenthaler M, Hofmann F, Du X (2003) A stimulatory role for cGMP-dependent protein kinase in platelet activation. Cell 112(1):77–86

    Article  PubMed  CAS  Google Scholar 

  257. Kleppisch T, Pfeifer A, Klatt P, Ruth P, Montkowski A, Fassler R, Hofmann F (1999) Long-term potentiation in the hippocampal CA1 region of mice lacking cGMP-dependent kinases is normal and susceptible to inhibition of nitric oxide synthase. J Neurosci 19(1):48–55

    PubMed  CAS  Google Scholar 

  258. Kleppisch T, Wolfsgruber W, Feil S, Allmann R, Wotjak CT, Goebbels S, Nave KA, Hofmann F, Feil R (2003) Hippocampal cGMP-dependent protein kinase I supports an age- and protein synthesis-dependent component of long-term potentiation but is not essential for spatial reference and contextual memory. J Neurosci 23(14):6005–6012

    PubMed  CAS  Google Scholar 

  259. Arancio O, Antonova I, Gambaryan S, Lohmann SM, Wood JS, Lawrence DS, Hawkins RD (2001) Presynaptic role of cGMP-dependent protein kinase during ­long-lasting potentiation. J Neurosci 21(1):143–149

    PubMed  CAS  Google Scholar 

  260. Song H, Ming G, He Z, Lehmann M, McKerracher L, Tessier-Lavigne M, Poo M (1998) Conversion of neuronal growth cone responses from repulsion to attraction by cyclic nucleotides. Science 281(5382):1515–1518

    Article  PubMed  CAS  Google Scholar 

  261. Schmidt H, Werner M, Heppenstall PA, Henning M, More MI, Kuhbandner S, Lewin GR, Hofmann F, Feil R, Rathjen FG (2002) cGMP-mediated signaling via cGKIalpha is required for the guidance and connectivity of sensory axons. J Cell Biol 159(3):489–498

    Article  PubMed  CAS  Google Scholar 

  262. Schmidt H, Stonkute A, Juttner R, Schaffer S, Buttgereit J, Feil R, Hofmann F, Rathjen FG (2007) The receptor guanylyl cyclase Npr2 is essential for sensory axon bifurcation within the spinal cord. J Cell Biol 179(2):331–340

    Article  PubMed  CAS  Google Scholar 

  263. Tegeder I, Del Turco D, Schmidtko A, Sausbier M, Feil R, Hofmann F, Deller T, Ruth P, Geisslinger G (2004) Reduced inflammatory hyperalgesia with preservation of acute thermal nociception in mice lacking cGMP-dependent protein kinase I. Proc Natl Acad Sci USA 101(9):3253–3257

    Article  PubMed  CAS  Google Scholar 

  264. Luo C, Gangadharan V, Bali KK, Xie RG, Agarwal N, Kurejova M, Tappe-Theodor A, Tegeder I, Feil S, Lewin G, Polgar E, Todd AJ, Schlossmann J, Hofmann F, Liu DL, Hu SJ, Feil R, Kuner T, Kuner R (2012) Presynaptically localized cyclic GMP-dependent protein kinase 1 is a key determinant of spinal synaptic potentiation and pain hypersensitivity. PLoS Biol 10(3):e1001283

    Article  PubMed  CAS  Google Scholar 

  265. Pfeifer A, Aszodi A, Seidler U, Ruth P, Hofmann F, Fassler R (1996) Intestinal secretory defects and dwarfism in mice lacking cGMP- dependent protein kinase II. Science 274(5295):2082–2086

    Article  PubMed  CAS  Google Scholar 

  266. Vaandrager AB, Smolenski A, Tilly BC, Houtsmuller AB, Ehlert EM, Bot AG, Edixhoven M, Boomaars WE, Lohmann SM, de Jonge HR (1998) Membrane targeting of cGMP-dependent protein kinase is required for cystic fibrosis transmembrane conductance regulator Cl- channel activation. Proc Natl Acad Sci USA 95(4):1466–1471

    Article  PubMed  CAS  Google Scholar 

  267. Vaandrager AB, Bot AG, Ruth P, Pfeifer A, Hofmann F, De Jonge HR (2000) Differential role of cyclic GMP-dependent protein kinase II in ion transport in murine small intestine and colon. Gastroenterology 118(1):108–114

    Article  PubMed  CAS  Google Scholar 

  268. Cha B, Kim JH, Hut H, Hogema BM, Nadarja J, Zizak M, Cavet M, Lee-Kwon W, Lohmann SM, Smolenski A, Tse CM, Yun C, de Jonge HR, Donowitz M (2005) cGMP inhibition of Na+/H+ antiporter 3 (NHE3) requires PDZ domain adapter NHERF2, a broad specificity protein kinase G-anchoring protein. J Biol Chem 280(17):16642–50

    Google Scholar 

  269. Foller M, Feil S, Ghoreschi K, Koka S, Gerling A, Thunemann M, Hofmann F, Schuler B, Vogel J, Pichler B, Kasinathan RS, Nicolay JP, Huber SM, Lang F, Feil R (2008) Anemia and splenomegaly in cGKI-deficient mice. Proc Natl Acad Sci USA 105(18):6771–6776. doi:10.1073/pnas.0708940105

    Article  PubMed  CAS  Google Scholar 

  270. Nikolaev VO, Gambaryan S, Engelhardt S, Walter U, Lohse MJ (2005) Real-time monitoring of the PDE2 activity of live cells: hormone-stimulated cAMP hydrolysis is faster than hormone-stimulated cAMP synthesis. J Biol Chem 280(3):1716–1719

    Article  PubMed  CAS  Google Scholar 

  271. MacFarland RT, Zelus BD, Beavo JA (1991) High concentrations of a cGMP-stimulated phosphodiesterase mediate ANP-induced decreases in cAMP and steroidogenesis in adrenal glomerulosa cells. J Biol Chem 266(1):136–142

    PubMed  CAS  Google Scholar 

  272. Kurtz A, Gotz KH, Hamann M, Wagner C (1998) Stimulation of renin secretion by nitric oxide is mediated by phosphodiesterase 3. Proc Natl Acad Sci USA 95(8):4743–4747

    Article  PubMed  CAS  Google Scholar 

  273. Henrich WL, McAllister EA, Smith PB, Campbell WB (1988) Guanosine 3′,5′-cyclic monophosphate as a mediator of inhibition of renin release. Am J Physiol 255(3 Pt 2):F474–F478

    PubMed  CAS  Google Scholar 

  274. Schricker K, Kurtz A (1993) Liberators of NO exert a dual effect on renin secretion from isolated mouse renal juxtaglomerular cells. Am J Physiol 265(2 Pt 2):F180–F186

    PubMed  CAS  Google Scholar 

  275. Gambaryan S, Hausler C, Markert T, Pohler D, Jarchau T, Walter U, Haase W, Kurtz A, Lohmann SM (1996) Expression of type II cGMP-dependent protein kinase in rat kidney is regulated by dehydration and correlated with renin gene expression. J Clin Invest 98(3):662–670

    Article  PubMed  CAS  Google Scholar 

  276. Wagner C, Pfeifer A, Ruth P, Hofmann F, Kurtz A (1998) Role of cGMP-kinase II in the control of renin secretion and renin expression. J Clin Invest 102(8):1576–1582

    Article  PubMed  CAS  Google Scholar 

  277. Gambaryan S, Butt E, Marcus K, Glazova M, Palmetshofer A, Guillon G, Smolenski A (2003) cGMP-dependent protein kinase type II regulates basal level of aldosterone production by zona glomerulosa cells without increasing expression of the steroidogenic acute regulatory protein gene. J Biol Chem 278(32):29640–29648

    Article  PubMed  CAS  Google Scholar 

  278. Spiessberger B, Bernhard D, Herrmann S, Feil S, Werner C, Luppa PB, Hofmann F (2009) cGMP-dependent protein kinase II and aldosterone secretion. FEBS J 276(4):1007–1013

    Article  PubMed  CAS  Google Scholar 

  279. Schinner E, Hofmann F, Schlossmann J (2012) Role of cGMP-dependent protein kinase I for kidney fibrosis. N-Schmied Arch Pharmacol 385(Suppl1):S81

    Google Scholar 

  280. Chusho H, Tamura N, Ogawa Y, Yasoda A, Suda M, Miyazawa T, Nakamura K, Nakao K, Kurihara T, Komatsu Y, Itoh H, Tanaka K, Saito Y, Katsuki M (2001) Dwarfism and early death in mice lacking C-type natriuretic peptide. Proc Natl Acad Sci USA 98(7):4016–4021

    Article  PubMed  CAS  Google Scholar 

  281. Yasoda A, Komatsu Y, Chusho H, Miyazawa T, Ozasa A, Miura M, Kurihara T, Rogi T, Tanaka S, Suda M, Tamura N, Ogawa Y, Nakao K (2004) Overexpression of CNP in chondrocytes rescues achondroplasia through a MAPK-dependent pathway. Nat Med 10(1):80–86

    Article  PubMed  CAS  Google Scholar 

  282. Talts JF, Pfeifer A, Hofmann F, Hunziker EB, Zhou XH, Aszodi A, Fassler R (1998) Endochondral ossification is dependent on the mechanical properties of cartilage tissue and on intracellular signals in chondrocytes. Ann N Y Acad Sci 857:74–85

    Article  PubMed  CAS  Google Scholar 

  283. Miyazawa T, Ogawa Y, Chusho H, Yasoda A, Tamura N, Komatsu Y, Pfeifer A, Hofmann F, Nakao K (2002) Cyclic GMP-dependent protein kinase II plays a critical role in C-type ­natriuretic peptide-mediated endochondral ossification. Endocrinology 143(9):3604–3610

    Article  PubMed  CAS  Google Scholar 

  284. Nakano Y, Nagamatsu Y, Ohshima Y (2004) cGMP and a germ-line signal control body size in C. elegans through cGMP-dependent protein kinase EGL-4. Genes Cells 9(9):773–779

    Article  PubMed  CAS  Google Scholar 

  285. Chikuda H, Kugimiya F, Hoshi K, Ikeda T, Ogasawara T, Shimoaka T, Kawano H, Kamekura S, Tsuchida A, Yokoi N, Nakamura K, Komeda K, Chung UI, Kawaguchi H (2004) Cyclic GMP-dependent protein kinase II is a molecular switch from proliferation to hypertrophic differentiation of chondrocytes. Genes Dev 18(19):2418–2429

    Article  PubMed  CAS  Google Scholar 

  286. Zhao X, Zhuang S, Chen Y, Boss GR, Pilz RB (2005) Cyclic GMP-dependent protein kinase regulates CCAAT enhancer-binding protein beta functions through inhibition of glycogen synthase kinase-3. J Biol Chem 280(38):32683–32692

    Article  PubMed  CAS  Google Scholar 

  287. Kawasaki Y, Kugimiya F, Chikuda H, Kamekura S, Ikeda T, Kawamura N, Saito T, Shinoda Y, Higashikawa A, Yano F, Ogasawara T, Ogata N, Hoshi K, Hofmann F, Woodgett JR, Nakamura K, Chung UI, Kawaguchi H (2008) Phosphorylation of GSK-3beta by cGMP-dependent protein kinase II promotes hypertrophic differentiation of murine chondrocytes. J Clin Invest 118(7):2506–2515

    PubMed  CAS  Google Scholar 

  288. Yaroslavskiy BB, Zhang Y, Kalla SE, Garcia Palacios V, Sharrow AC, Li Y, Zaidi M, Wu C, Blair HC (2005) NO-dependent osteoclast motility: reliance on cGMP-dependent protein kinase I and VASP. J Cell Sci 118(Pt 23):5479–5487

    Article  PubMed  CAS  Google Scholar 

  289. Yaroslavskiy BB, Turkova I, Wang Y, Robinson LJ, Blair HC (2010) Functional osteoclast attachment requires inositol-1,4,5-trisphosphate receptor-associated cGMP-dependent kinase substrate. Lab Invest 90(10):1533–1542

    Article  PubMed  CAS  Google Scholar 

  290. Lenz A, Bennett M, Skelton WP, Vesely DL (2010) Vessel dilator and C-type natriuretic peptide enhance the proliferation of human osteoblasts. Pediatr Res 68(5):405–408

    PubMed  CAS  Google Scholar 

  291. Rangaswami H, Schwappacher R, Marathe N, Zhuang S, Casteel DE, Haas B, Chen Y, Pfeifer A, Kato H, Shattil S, Boss GR, Pilz RB (2010) Cyclic GMP and protein kinase G control a Src-containing mechanosome in osteoblasts. Sci Signal 3(153):ra91

    Article  PubMed  CAS  Google Scholar 

  292. Marathe N, Rangaswami H, Zhuang S, Boss GR, Pilz RB (2012) Pro-survival effects of 17beta-estradiol on osteocytes are mediated by nitric oxide/cGMP via differential actions of cGMP-dependent protein kinases I and II. J Biol Chem 287(2):978–988

    Article  PubMed  CAS  Google Scholar 

  293. Chow JW, Fox SW, Lean JM, Chambers TJ (1998) Role of nitric oxide and prostaglandins in mechanically induced bone formation. J Bone Miner Res 13(6):1039–1044

    Article  PubMed  CAS  Google Scholar 

  294. Spinas GA, Laffranchi R, Francoys I, David I, Richter C, Reinecke M (1998) The early phase of glucose-stimulated insulin secretion requires nitric oxide. Diabetologia 41(3):292–299

    Article  PubMed  CAS  Google Scholar 

  295. Panagiotidis G, Alm P, Lundquist I (1992) Inhibition of islet nitric oxide synthase increases arginine-induced insulin release. Eur J Pharmacol 229(2–3):277–278

    Article  PubMed  CAS  Google Scholar 

  296. Alm P, Ekstrom P, Henningsson R, Lundquist I (1999) Morphological evidence for the existence of nitric oxide and carbon monoxide pathways in the rat islets of Langerhans: an immunocytochemical and confocal microscopical study. Diabetologia 42(8):978–986

    Article  PubMed  CAS  Google Scholar 

  297. Schmidt HH, Warner TD, Ishii K, Sheng H, Murad F (1992) Insulin secretion from ­pancreatic B cells caused by L-arginine-derived nitrogen oxides. Science 255(5045):721–723

    Article  PubMed  CAS  Google Scholar 

  298. Salehi A, Carlberg M, Henningson R, Lundquist I (1996) Islet constitutive nitric oxide synthase: biochemical determination and regulatory function. Am J Physiol 270(6 Pt 1):C1634–C1641

    PubMed  CAS  Google Scholar 

  299. Leiss V, Friebe A, Welling A, Hofmann F, Lukowski R (2011) Cyclic GMP kinase I modulates glucagon release from pancreatic alpha-cells. Diabetes 60(1):148–156

    Article  PubMed  CAS  Google Scholar 

  300. Lutz SZ, Hennige AM, Feil S, Peter A, Gerling A, Machann J, Krober SM, Rath M, Schurmann A, Weigert C, Haring HU, Feil R (2011) Genetic ablation of cGMP-dependent protein kinase type I causes liver inflammation and fasting hyperglycemia. Diabetes 60(5):1566–1576

    Article  PubMed  CAS  Google Scholar 

  301. Haas B, Mayer P, Jennissen K, Scholz D, Berriel Diaz M, Bloch W, Herzig S, Fassler R, Pfeifer A (2009) Protein kinase G controls brown fat cell differentiation and mitochondrial biogenesis. Sci Signal 2(99):ra78. doi:10.1126/scisignal.2000511

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

Research in the author’s laboratories was supported by German Research Foundation (DFG) and Fond der Chemischen Industrie.

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Authors and Affiliations

  1. FOR 923, Institut für Pharmakologie und Toxikologie, der Technischen Universität München, Munich, Germany

    Franz Hofmann & Jörg W. Wegener

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  1. Franz Hofmann
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  2. Jörg W. Wegener
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  1. Addenbrooke’s Hospital, Department of Medicine, University of Cambridge, Hills Road, Cambridge, CB2 2QQ, United Kingdom

    Thomas Krieg

  2. Toxicology and Clinical Pharmacy, Department of Pharmacology, Universität Tübingen, Auf der Morgenstelle 8, Tübingen, 72076, Germany

    Robert Lukowski

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Hofmann, F., Wegener, J.W. (2013). cGMP-Dependent Protein Kinases (cGK). In: Krieg, T., Lukowski, R. (eds) Guanylate Cyclase and Cyclic GMP. Methods in Molecular Biology, vol 1020. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-459-3_2

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  • DOI: https://doi.org/10.1007/978-1-62703-459-3_2

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  • Print ISBN: 978-1-62703-458-6

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