Entry
Name
cGMP-PKG signaling pathway - Odobenus rosmarus divergens (Pacific walrus)
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
Odobenus rosmarus divergens (Pacific walrus) [GN:
oro ]
Gene
101384596 GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634 ]
101385358 GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635 ]
101371250 GNA12; guanine nucleotide-binding protein subunit alpha-12 isoform X1 [KO:K04346 ]
101386508 GNA13; guanine nucleotide-binding protein subunit alpha-13 isoform X1 [KO:K04639 ]
101381341 TRPC6; short transient receptor potential channel 6 isoform X1 [KO:K04969 ]
101363063 PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
101363831 PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X2 [KO:K04348 ] [EC:3.1.3.16 ]
101385000 PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X2 [KO:K04348 ] [EC:3.1.3.16 ]
101382818 MEF2A; myocyte-specific enhancer factor 2A isoform X3 [KO:K09260 ]
101370419 MEF2C; myocyte-specific enhancer factor 2C isoform X1 [KO:K04454 ]
101378849 MEF2D; myocyte-specific enhancer factor 2D isoform X1 [KO:K09262 ]
101385449 NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446 ]
101379396 NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332 ]
101378978 NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333 ]
101373256 NFATC4; nuclear factor of activated T-cells, cytoplasmic 4 isoform X2 [KO:K17334 ]
101365624 CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850 ]
101383514 CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851 ]
101364481 CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853 ]
101385947 CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857 ]
101374985 KCNMA1; calcium-activated potassium channel subunit alpha-1 isoform X1 [KO:K04936 ]
101373053 LOW QUALITY PROTEIN: potassium channel subfamily U member 1-like [KO:K05274 ]
101381979 KCNMB1; calcium-activated potassium channel subunit beta-1 [KO:K04937 ]
101371468 KCNMB2; calcium-activated potassium channel subunit beta-2 [KO:K04938 ]
101365723 KCNMB4; calcium-activated potassium channel subunit beta-4 [KO:K04941 ]
101368218 ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 isoform X1 [KO:K01540 ]
101377129 ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540 ]
101362729 ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540 ]
101382690 FXYD2; sodium/potassium-transporting ATPase subunit gamma isoform X2 [KO:K01538 ]
101375710 PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
101386162 PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X2 [KO:K05858 ] [EC:3.1.4.11 ]
101386750 PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
101367743 ITPR1; inositol 1,4,5-trisphosphate receptor type 1 isoform X1 [KO:K04958 ]
101380808 ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X2 [KO:K04960 ]
101384536 PPP1R12A; protein phosphatase 1 regulatory subunit 12A isoform X2 [KO:K06270 ]
101382867 PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit isoform X1 [KO:K06269 ] [EC:3.1.3.16 ]
101372346 PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit isoform X1 [KO:K06269 ] [EC:3.1.3.16 ]
101386053 PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit isoform X1 [KO:K06269 ] [EC:3.1.3.16 ]
101384567 CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183 ]
101362788 MYL9; myosin regulatory light polypeptide 9 isoform X1 [KO:K12755 ]
101376186 GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 isoform X1 [KO:K04630 ]
101367568 GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630 ]
101367936 GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 isoform X1 [KO:K04630 ]
101371781 IRS4; LOW QUALITY PROTEIN: insulin receptor substrate 4 [KO:K17446 ]
101362272 PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform isoform X1 [KO:K21289 ] [EC:2.7.1.153 ]
101374579 PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 [KO:K21290 ]
101375062 PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 [KO:K21290 ]
101367960 KCNJ8; ATP-sensitive inward rectifier potassium channel 8 [KO:K05001 ]
101375766 VDAC1; voltage-dependent anion-selective channel protein 1 isoform X2 [KO:K05862 ]
101374903 VDAC2; voltage-dependent anion-selective channel protein 2 isoform X1 [KO:K15040 ]
101374285 VDAC3; voltage-dependent anion-selective channel protein 3 isoform X2 [KO:K15041 ]
101374369 voltage-dependent anion-selective channel protein 3-like [KO:K15041 ]
101383024 CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870 ]
101374034 ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450 ]
101368122 ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374 ]
101383806 CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048 ]
101385783 CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048 ]
101376293 CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X2 [KO:K09048 ]
101381943 CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048 ]
101385675 CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048 ]
101384862 CREB5; cyclic AMP-responsive element-binding protein 5 [KO:K09047 ]
101381436 ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X2 [KO:K09049 ]
101378347 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
oro04270 Vascular smooth muscle contraction
KO pathway
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