Entry Name cGMP-PKG signaling pathway - Alexandromys fortis (reed vole)
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 transductionBRITE hierarchy
Pathway map Ortholog table Other DBs Organism Alexandromys fortis (reed vole) [GN:
mfot ]
Gene 126510731 guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634 ]
126513704 short transient receptor potential channel 6 isoform X1 [KO:K04969 ]
126491367 serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
126515387 nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446 ]
126487431 nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332 ]
126502736 nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333 ]
126505446 voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850 ]
126511130 voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851 ]
126512843 LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1F [KO:K04853 ]
126505025 voltage-dependent L-type calcium channel subunit alpha-1S isoform X1 [KO:K04857 ]
126491556 calcium-activated potassium channel subunit alpha-1 isoform X1 [KO:K04936 ]
126510063 sodium/potassium-transporting ATPase subunit gamma isoform X1 [KO:K01538 ]
126514463 inositol 1,4,5-triphosphate receptor associated 1 isoform X1 [KO:K12337 ]
126497496 protein phosphatase 1 regulatory subunit 12A isoform X1 [KO:K06270 ]
126512093 guanine nucleotide-binding protein G(i) subunit alpha-3-like [KO:K04630 ]
126499907 guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630 ]
126500134 guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630 ]
126487932 guanine nucleotide-binding protein G(i) subunit alpha-3 isoform X1 [KO:K04630 ]
126514078 phosphoinositide 3-kinase regulatory subunit 5 isoform X1 [KO:K21290 ]
126509080 LOW QUALITY PROTEIN: voltage-dependent anion-selective channel protein 2-like [KO:K15040 ]
126508777 cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870 ]
126487367 cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450 ]
126486506 cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048 ]
126489302 cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048 ]
126489793 cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048 ]
126505257 cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048 ]
126509567 cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047 ]
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 KO pathway LinkDB All DBs
