Entry
Name
cGMP-PKG signaling pathway - Phocoena sinus (vaquita)
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
Phocoena sinus (vaquita) [GN:
psiu ]
Gene
116741630 ADRA2A; LOW QUALITY PROTEIN: alpha-2A adrenergic receptor [KO:K04138 ]
116755414 GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634 ]
116751212 GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635 ]
116739840 GNA12; guanine nucleotide-binding protein subunit alpha-12 [KO:K04346 ]
116745371 GNA13; guanine nucleotide-binding protein subunit alpha-13 [KO:K04639 ]
116757835 TRPC6; short transient receptor potential channel 6 isoform X1 [KO:K04969 ]
116753887 PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
116755228 PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
116741444 PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
116755488 PPP3R2; LOW QUALITY PROTEIN: calcineurin subunit B type 2 [KO:K06268 ]
116748703 MEF2A; myocyte-specific enhancer factor 2A isoform X1 [KO:K09260 ]
116751387 MEF2B; myocyte-specific enhancer factor 2B isoform X1 [KO:K09261 ]
116751618 MEF2C; myocyte-specific enhancer factor 2C isoform X1 [KO:K04454 ]
116751811 MEF2D; myocyte-specific enhancer factor 2D isoform X1 [KO:K09262 ]
116765202 NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446 ]
116740306 NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332 ]
116744362 NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333 ]
116749495 NFATC4; nuclear factor of activated T-cells, cytoplasmic 4 isoform X1 [KO:K17334 ]
116760103 CACNA1C; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850 ]
116762723 CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851 ]
116747382 CACNA1F; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853 ]
116739924 CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857 ]
116741577 KCNMA1; LOW QUALITY PROTEIN: calcium-activated potassium channel subunit alpha-1 [KO:K04936 ]
116752020 KCNMB1; calcium-activated potassium channel subunit beta-1 [KO:K04937 ]
116753263 KCNMB2; calcium-activated potassium channel subunit beta-2 [KO:K04938 ]
116760350 KCNMB4; calcium-activated potassium channel subunit beta-4 [KO:K04941 ]
116753189 ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 isoform X1 [KO:K01540 ]
116746443 ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 isoform X1 [KO:K01540 ]
116758266 LOW QUALITY PROTEIN: sodium/potassium-transporting ATPase subunit beta-3-like [KO:K01540 ]
116758154 FXYD2; sodium/potassium-transporting ATPase subunit gamma isoform X1 [KO:K01538 ]
116749106 PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
116740640 PLCB1; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858 ] [EC:3.1.4.11 ]
116761601 ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958 ]
116760890 ITPR2; inositol 1,4,5-trisphosphate receptor type 2 isoform X1 [KO:K04959 ]
116761675 ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960 ]
116760401 PPP1R12A; LOW QUALITY PROTEIN: protein phosphatase 1 regulatory subunit 12A [KO:K06270 ]
116739009 PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit isoform X1 [KO:K06269 ] [EC:3.1.3.16 ]
116764122 PPP1CB; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269 ] [EC:3.1.3.16 ]
116748386 CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183 ]
116740323 MYL9; myosin regulatory light polypeptide 9 isoform X1 [KO:K12755 ]
116761812 GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 isoform X1 [KO:K04630 ]
116749946 GNAI3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630 ]
116759318 GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630 ]
116759199 PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform isoform X1 [KO:K21289 ] [EC:2.7.1.153 ]
116746412 PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 isoform X1 [KO:K21290 ]
116745258 PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 isoform X1 [KO:K21290 ]
116760014 KCNJ8; LOW QUALITY PROTEIN: ATP-sensitive inward rectifier potassium channel 8 [KO:K05001 ]
116741397 LOW QUALITY PROTEIN: voltage-dependent anion-selective channel protein 1-like [KO:K05862 ]
116751471 VDAC1; voltage-dependent anion-selective channel protein 1 isoform X1 [KO:K05862 ]
116746828 VDAC3; voltage-dependent anion-selective channel protein 3 [KO:K15041 ]
116746894 LOW QUALITY PROTEIN: voltage-dependent anion-selective channel protein 3-like [KO:K15041 ]
116761135 LOW QUALITY PROTEIN: voltage-dependent anion-selective channel protein 3-like [KO:K15041 ]
116756730 CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870 ]
116756632 ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450 ]
116761029 ATF4; cyclic AMP-dependent transcription factor ATF-4 isoform X1 [KO:K04374 ]
116755320 CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048 ]
116740243 CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048 ]
116758621 CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048 ]
116751955 CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048 ]
116759300 CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048 ]
116759616 CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047 ]
116762930 ATF6B; LOW QUALITY PROTEIN: cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049 ]
116743554 VASP; vasodilator-stimulated phosphoprotein isoform X1 [KO:K06274 ]
116747589 MAP2K1; LOW QUALITY PROTEIN: dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368 ] [EC:2.7.12.2 ]
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
KO pathway
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