Entry
Name
cGMP-PKG signaling pathway - Otolemur garnettii (small-eared galago)
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
Otolemur garnettii (small-eared galago) [GN:
oga ]
Gene
100946783 GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634 ]
100949562 GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635 ]
100956403 GNA12; guanine nucleotide-binding protein subunit alpha-12 [KO:K04346 ]
100963709 GNA13; guanine nucleotide-binding protein subunit alpha-13 [KO:K04639 ]
100946652 TRPC6; short transient receptor potential channel 6 isoform X1 [KO:K04969 ]
100961754 PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
100961025 PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform [KO:K04348 ] [EC:3.1.3.16 ]
100945846 PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X2 [KO:K04348 ] [EC:3.1.3.16 ]
100942688 MEF2A; myocyte-specific enhancer factor 2A isoform X2 [KO:K09260 ]
100959309 MEF2C; myocyte-specific enhancer factor 2C isoform X2 [KO:K04454 ]
100940498 NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446 ]
100955220 NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X2 [KO:K17332 ]
100966615 NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 [KO:K17333 ]
100950273 NFATC4; nuclear factor of activated T-cells, cytoplasmic 4 isoform X1 [KO:K17334 ]
100964267 CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850 ]
100953767 CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X2 [KO:K04851 ]
100962519 CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853 ]
100962683 CACNA1S; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857 ]
100966844 KCNMA1; calcium-activated potassium channel subunit alpha-1 isoform X1 [KO:K04936 ]
100945387 KCNU1; LOW QUALITY PROTEIN: potassium channel subfamily U member 1 [KO:K05274 ]
100950654 KCNMB1; calcium-activated potassium channel subunit beta-1 [KO:K04937 ]
100955254 KCNMB2; calcium-activated potassium channel subunit beta-2 [KO:K04938 ]
100961968 KCNMB3; calcium-activated potassium channel subunit beta-3 [KO:K04939 ]
100949380 KCNMB4; calcium-activated potassium channel subunit beta-4 [KO:K04941 ]
100958465 ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540 ]
100947982 ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540 ]
100964465 ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540 ]
100962702 FXYD2; sodium/potassium-transporting ATPase subunit gamma [KO:K01538 ]
100966182 PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X2 [KO:K05858 ] [EC:3.1.4.11 ]
100953462 PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X2 [KO:K05858 ] [EC:3.1.4.11 ]
100964437 ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958 ]
100955707 PPP1R12A; protein phosphatase 1 regulatory subunit 12A isoform X1 [KO:K06270 ]
100962114 GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630 ]
100945007 GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630 ]
100962000 GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 isoform X2 [KO:K04630 ]
100951299 IRS2; LOW QUALITY PROTEIN: insulin receptor substrate 2 [KO:K07187 ]
100950470 PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289 ] [EC:2.7.1.153 ]
100950920 PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 [KO:K21290 ]
100951247 PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 [KO:K21290 ]
100949788 KCNJ8; ATP-sensitive inward rectifier potassium channel 8 [KO:K05001 ]
100948868 VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862 ]
100962937 VDAC2; voltage-dependent anion-selective channel protein 2 isoform X1 [KO:K15040 ]
100945532 VDAC3; voltage-dependent anion-selective channel protein 3 [KO:K15041 ]
100964324 CREB1; cyclic AMP-responsive element-binding protein 1 isoform X2 [KO:K05870 ]
100966891 ATF2; cyclic AMP-dependent transcription factor ATF-2 [KO:K04450 ]
100940993 ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374 ]
100966324 CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048 ]
100951671 CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048 ]
100941510 CREB3; LOW QUALITY PROTEIN: cyclic AMP-responsive element-binding protein 3 [KO:K09048 ]
100955062 CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048 ]
100952085 CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048 ]
100952718 CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047 ]
100951769 ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X2 [KO:K09049 ]
100961047 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
oga04270 Vascular smooth muscle contraction
KO pathway
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