Entry Name cGMP-PKG signaling pathway - Pteropus vampyrus (large flying fox)
Description Cyclic GMP (cGMP) is the intracellular second messenger that mediates the action of nitric oxide (NO) and natriuretic peptides (NPs), regulating a broad array of physiologic processes. The elevated intracellular cGMP level exerts its physiological action through two forms of cGMP-dependent protein kinase (PKG), cGMP-regulated phosphodiesterases (PDE2, PDE3) and cGMP-gated cation channels, among which PKGs might be the primary mediator. PKG1 isoform-specific activation of established substrates leads to reduction of cytosolic calcium concentration and/or decrease in the sensitivity of myofilaments to Ca2+ (Ca2+-desensitization), resulting in smooth muscle relaxation. In cardiac myocyte, PKG directly phosphorylates a member of the transient potential receptor canonical channel family, TRPC6, suppressing this nonselective ion channel's Ca2+ conductance, G-alpha-q agonist-induced NFAT activation, and myocyte hypertrophic responses. PKG also opens mitochondrial ATP-sensitive K+ (mitoKATP) channels and subsequent release of ROS triggers cardioprotection.
Class Environmental Information Processing; Signal transductionBRITE hierarchy
Pathway map Other DBs Organism Pteropus vampyrus (large flying fox) [GN:
pvp ]
Gene 105288852 PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
105288878 VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040 ]
105288884 KCNMA1; calcium-activated potassium channel subunit alpha-1 isoform X2 [KO:K04936 ]
105290070 CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048 ]
105290195 ATF2; cyclic AMP-dependent transcription factor ATF-2 [KO:K04450 ]
105290256 MEF2A; myocyte-specific enhancer factor 2A isoform X1 [KO:K09260 ]
105290354 ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540 ]
105291225 ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540 ]
105291261 PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 isoform X1 [KO:K21290 ]
105291351 PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 [KO:K21290 ]
105291472 ADRB1; LOW QUALITY PROTEIN: beta-1 adrenergic receptor [KO:K04141 ]
105291624 CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048 ]
105293031 PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
105293648 VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862 ]
105294560 GNA12; guanine nucleotide-binding protein subunit alpha-12 isoform X1 [KO:K04346 ]
105295155 GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630 ]
105295517 GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630 ]
105296040 NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332 ]
105296460 CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048 ]
105296533 PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
105296936 CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857 ]
105297202 GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630 ]
105297298 CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850 ]
105297337 VASP; vasodilator-stimulated phosphoprotein isoform X6 [KO:K06274 ]
105297699 GNA13; guanine nucleotide-binding protein subunit alpha-13 [KO:K04639 ]
105298070 ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374 ]
105298272 TRPC6; short transient receptor potential channel 6 isoform X1 [KO:K04969 ]
105298404 CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870 ]
105298737 PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
105299132 PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit isoform X1 [KO:K06269 ] [EC:3.1.3.16 ]
105299311 KCNMB1; calcium-activated potassium channel subunit beta-1 [KO:K04937 ]
105300332 PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289 ] [EC:2.7.1.153 ]
105300436 GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635 ]
105300538 VDAC3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041 ]
105301539 KCNMB4; calcium-activated potassium channel subunit beta-4 [KO:K04941 ]
105301889 PPP1R12A; protein phosphatase 1 regulatory subunit 12A isoform X3 [KO:K06270 ]
105303020 NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446 ]
105303959 MEF2C; myocyte-specific enhancer factor 2C isoform X1 [KO:K04454 ]
105304363 CACNA1D; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851 ]
105305286 ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049 ]
105305747 NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333 ]
105306466 CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048 ]
105306534 KCNJ8; ATP-sensitive inward rectifier potassium channel 8 [KO:K05001 ]
105306745 CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048 ]
105307584 KCNMB3; calcium-activated potassium channel subunit beta-3 isoform X3 [KO:K04939 ]
105307616 KCNMB2; calcium-activated potassium channel subunit beta-2 [KO:K04938 ]
105308975 ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540 ]
105309056 CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853 ]
105309403 NFATC4; nuclear factor of activated T-cells, cytoplasmic 4 [KO:K17334 ]
105309689 CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183 ]
Compound C01245 D-myo-Inositol 1,4,5-trisphosphate
Reference Authors Francis SH, Busch JL, Corbin JD, Sibley D
Title cGMP-dependent protein kinases and cGMP phosphodiesterases in nitric oxide and cGMP action.
Journal Reference Authors Feil R, Kemp-Harper B
Title cGMP signalling: from bench to bedside. Conference on cGMP generators, effectors and therapeutic implications.
Journal Reference Authors Takimoto E
Title Cyclic GMP-dependent signaling in cardiac myocytes.
Journal Reference Authors Hofmann F, Feil R, Kleppisch T, Schlossmann J
Title Function of cGMP-dependent protein kinases as revealed by gene deletion.
Journal Reference Authors Kuebler WM
Title The Janus-faced regulation of endothelial permeability by cyclic GMP.
Journal Reference Authors Schlossmann J, Desch M
Title IRAG and novel PKG targeting in the cardiovascular system.
Journal Reference Authors Murthy KS
Title Signaling for contraction and relaxation in smooth muscle of the gut.
Journal Reference Authors Sanders KM, Koh SD, Ro S, Ward SM
Title Regulation of gastrointestinal motility--insights from smooth muscle biology.
Journal Reference Authors Gao Y
Title The multiple actions of NO.
Journal Reference Authors Wang X, Robinson PJ
Title Cyclic GMP-dependent protein kinase and cellular signaling in the nervous system.
Journal Reference Authors Tsai EJ, Kass DA
Title Cyclic GMP signaling in cardiovascular pathophysiology and therapeutics.
Journal Reference Authors Villanueva C, Giulivi C
Title Subcellular and cellular locations of nitric oxide synthase isoforms as determinants of health and disease.
Journal Reference Authors Schlossmann J, Hofmann F
Title cGMP-dependent protein kinases in drug discovery.
Journal Reference Authors Kass DA, Champion HC, Beavo JA
Title Phosphodiesterase type 5: expanding roles in cardiovascular regulation.
Journal Reference Authors Uckert S, Hedlund P, Andersson KE, Truss MC, Jonas U, Stief CG
Title Update on phosphodiesterase (PDE) isoenzymes as pharmacologic targets in urology: present and future.
Journal Reference Authors Yan C, Kim D, Aizawa T, Berk BC
Title Functional interplay between angiotensin II and nitric oxide: cyclic GMP as a key mediator.
Journal Reference Authors McKinsey TA, Kass DA
Title Small-molecule therapies for cardiac hypertrophy: moving beneath the cell surface.
Journal Reference Authors Koitabashi N, Aiba T, Hesketh GG, Rowell J, Zhang M, Takimoto E, Tomaselli GF, Kass DA
Title 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.
Journal Reference Authors Costa AD, Pierre SV, Cohen MV, Downey JM, Garlid KD
Title cGMP signalling in pre- and post-conditioning: the role of mitochondria.
Journal Reference Authors Boengler K, Schulz R, Heusch G
Title Loss of cardioprotection with ageing.
Journal Reference Authors Gao Y, Portugal AD, Liu J, Negash S, Zhou W, Tian J, Xiang R, Longo LD, Raj JU
Title Preservation of cGMP-induced relaxation of pulmonary veins of fetal lambs exposed to chronic high altitude hypoxia: role of PKG and Rho kinase.
Journal Reference Authors Li Z, Xi X, Du X
Title A mitogen-activated protein kinase-dependent signaling pathway in the activation of platelet integrin alpha IIbbeta3.
Journal Reference Authors Xie J, Cha SK, An SW, Kuro-O M, Birnbaumer L, Huang CL
Title Cardioprotection by Klotho through downregulation of TRPC6 channels in the mouse heart.
Journal Related pvp04270 Vascular smooth muscle contraction
KO pathway
