Entry
Name
cGMP-PKG signaling pathway - Desmodus rotundus (common vampire bat)
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
Desmodus rotundus (common vampire bat) [GN:
dro ]
Gene
112300359 guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634 ]
112312418 GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635 ]
112319524 GNA12; guanine nucleotide-binding protein subunit alpha-12 [KO:K04346 ]
112316266 GNA13; guanine nucleotide-binding protein subunit alpha-13 [KO:K04639 ]
112317520 TRPC6; short transient receptor potential channel 6 isoform X1 [KO:K04969 ]
112305449 PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
112317863 PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform [KO:K04348 ] [EC:3.1.3.16 ]
112305248 PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
112305862 MEF2A; myocyte-specific enhancer factor 2A isoform X1 [KO:K09260 ]
112307451 MEF2C; myocyte-specific enhancer factor 2C isoform X1 [KO:K04454 ]
112322654 NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446 ]
112303992 NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 [KO:K17332 ]
112300806 NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333 ]
112300562 NFATC4; nuclear factor of activated T-cells, cytoplasmic 4 isoform X1 [KO:K17334 ]
112309331 CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850 ]
112301160 CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851 ]
112322357 CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853 ]
112318756 CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857 ]
112305509 KCNMA1; calcium-activated potassium channel subunit alpha-1 isoform X1 [KO:K04936 ]
112306690 KCNU1; LOW QUALITY PROTEIN: potassium channel subfamily U member 1 [KO:K05274 ]
112319583 KCNMB1; calcium-activated potassium channel subunit beta-1 [KO:K04937 ]
112304981 KCNMB2; calcium-activated potassium channel subunit beta-2 [KO:K04938 ]
112307674 KCNMB3; calcium-activated potassium channel subunit beta-3 isoform X1 [KO:K04939 ]
112319148 KCNMB4; calcium-activated potassium channel subunit beta-4 [KO:K04941 ]
112308526 ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540 ]
112301115 ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540 ]
112298654 ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540 ]
112314310 FXYD2; sodium/potassium-transporting ATPase subunit gamma isoform X1 [KO:K01538 ]
112304122 PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
112311437 PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
112304255 PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
112318382 ITPR2; LOW QUALITY PROTEIN: inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959 ]
112322163 PPP1R12A; protein phosphatase 1 regulatory subunit 12A isoform X1 [KO:K06270 ]
112311702 CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183 ]
112296715 CNGB1; LOW QUALITY PROTEIN: cyclic nucleotide-gated cation channel beta-1 [KO:K04952 ]
112313520 GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630 ]
112303430 GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630 ]
112309828 GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630 ]
112296869 IRS4; LOW QUALITY PROTEIN: insulin receptor substrate 4 [KO:K17446 ]
112303039 PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [KO:K21289 ] [EC:2.7.1.153 ]
112308895 PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 [KO:K21290 ]
112308643 PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 [KO:K21290 ]
112318626 KCNJ8; ATP-sensitive inward rectifier potassium channel 8 [KO:K05001 ]
112318103 VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862 ]
112303041 LOW QUALITY PROTEIN: voltage-dependent anion-selective channel protein 2-like [KO:K15040 ]
112305359 VDAC2; LOW QUALITY PROTEIN: voltage-dependent anion-selective channel protein 2 [KO:K15040 ]
112321447 VDAC3; voltage-dependent anion-selective channel protein 3 [KO:K15041 ]
112307981 CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870 ]
112305718 ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450 ]
112321682 ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374 ]
112304550 CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048 ]
112303463 CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048 ]
112299769 CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048 ]
112312688 CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048 ]
112316383 CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048 ]
112306927 CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047 ]
112302085 ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049 ]
112312938 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
dro04270 Vascular smooth muscle contraction
KO pathway
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