Entry
Name
cGMP-PKG signaling pathway - Nyctereutes procyonoides (raccoon dog)
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 transduction
BRITE hierarchy
Pathway map
Ortholog table
Other DBs
Organism
Nyctereutes procyonoides (raccoon dog) [GN:
npo ]
Gene
129500644 GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634 ]
129522061 GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635 ]
129519699 GNA12; guanine nucleotide-binding protein subunit alpha-12 [KO:K04346 ]
129510400 GNA13; guanine nucleotide-binding protein subunit alpha-13 [KO:K04639 ]
129496617 TRPC6; short transient receptor potential channel 6 isoform X1 [KO:K04969 ]
129523448 PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
129509604 PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
129510149 MEF2A; myocyte-specific enhancer factor 2A isoform X1 [KO:K09260 ]
129501658 MEF2C; myocyte-specific enhancer factor 2C isoform X1 [KO:K04454 ]
129508749 MEF2D; myocyte-specific enhancer factor 2D isoform X1 [KO:K09262 ]
129495445 NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446 ]
129514485 nuclear factor of activated T-cells, cytoplasmic 1-like isoform X1 [KO:K04446 ]
129496345 NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332 ]
129497947 NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333 ]
129499558 NFATC4; nuclear factor of activated T-cells, cytoplasmic 4 [KO:K17334 ]
129503382 CACNA1C; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850 ]
129521343 CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851 ]
129517804 CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853 ]
129505985 CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857 ]
129509862 KCNMA1; LOW QUALITY PROTEIN: calcium-activated potassium channel subunit alpha-1 [KO:K04936 ]
129509988 KCNMB1; calcium-activated potassium channel subunit beta-1 [KO:K04937 ]
129498378 KCNMB2; calcium-activated potassium channel subunit beta-2 [KO:K04938 ]
129498351 KCNMB3; calcium-activated potassium channel subunit beta-3 [KO:K04939 ]
129511245 KCNMB4; calcium-activated potassium channel subunit beta-4 [KO:K04941 ]
129501310 ATP1A1; LOW QUALITY PROTEIN: sodium/potassium-transporting ATPase subunit alpha-1 [KO:K01539 ] [EC:7.2.2.13 ]
129508607 ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540 ]
129496654 ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540 ]
129507194 ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540 ]
129496894 PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
129504276 PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
129497646 PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
129521608 ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958 ]
129512495 ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960 ]
129504982 IRAG1; inositol 1,4,5-triphosphate receptor associated 1 isoform X1 [KO:K12337 ]
129520637 PPP1R12A; protein phosphatase 1 regulatory subunit 12A isoform X1 [KO:K06270 ]
129508013 PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit isoform X1 [KO:K06269 ] [EC:3.1.3.16 ]
129503326 myosin regulatory light polypeptide 9-like isoform X1 [KO:K12755 ]
129513801 CNGB1; LOW QUALITY PROTEIN: cyclic nucleotide-gated cation channel beta-1 [KO:K04952 ]
129494269 GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630 ]
129519569 GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630 ]
129522106 GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630 ]
129494039 PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289 ] [EC:2.7.1.153 ]
129496567 PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 isoform X1 [KO:K21290 ]
129497926 PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 isoform X1 [KO:K21290 ]
129523256 ADRB1; LOW QUALITY PROTEIN: beta-1 adrenergic receptor [KO:K04141 ]
129505587 KCNJ8; ATP-sensitive inward rectifier potassium channel 8 [KO:K05001 ]
129495115 VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862 ]
129509516 VDAC2; LOW QUALITY PROTEIN: voltage-dependent anion-selective channel protein 2 [KO:K15040 ]
129516170 VDAC3; voltage-dependent anion-selective channel protein 3 [KO:K15041 ]
129522997 CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870 ]
129498595 ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450 ]
129511576 ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374 ]
129508719 CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048 ]
129494799 CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048 ]
129503105 CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048 ]
129515926 CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048 ]
129522278 CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048 ]
129502771 CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047 ]
129513003 ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049 ]
129500860 VASP; vasodilator-stimulated phosphoprotein isoform X1 [KO:K06274 ]
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 pathway
npo04270 Vascular smooth muscle contraction
KO pathway
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