Entry Name cGMP-PKG signaling pathway - Ursus maritimus (polar bear)
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 Other DBs Organism Ursus maritimus (polar bear) [GN:
umr ]
Gene 103656392 IRAG1; inositol 1,4,5-triphosphate receptor associated 1 isoform X2 [KO:K12337 ]
103656975 KCNMB4; calcium-activated potassium channel subunit beta-4 [KO:K04941 ]
103657769 CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857 ]
103658473 NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446 ]
103658775 GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630 ]
103659180 EDNRB; LOW QUALITY PROTEIN: endothelin receptor type B [KO:K04198 ]
103659593 ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450 ]
103659802 CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870 ]
103660041 MEF2A; myocyte-specific enhancer factor 2A isoform X1 [KO:K09260 ]
103660367 ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540 ]
103660496 PIK3R6; phosphoinositide 3-kinase regulatory subunit 6 [KO:K21290 ]
103660497 PIK3R5; phosphoinositide 3-kinase regulatory subunit 5 [KO:K21290 ]
103663281 GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634 ]
103663818 VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862 ]
103664498 KCNMB1; calcium-activated potassium channel subunit beta-1 [KO:K04937 ]
103665232 KCNJ8; ATP-sensitive inward rectifier potassium channel 8 [KO:K05001 ]
103665670 GNA13; guanine nucleotide-binding protein subunit alpha-13 [KO:K04639 ]
103667087 CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048 ]
103667625 CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853 ]
103667825 PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
103667846 VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040 ]
103668030 KCNMA1; calcium-activated potassium channel subunit alpha-1 [KO:K04936 ]
103668409 CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048 ]
103668685 MEF2D; myocyte-specific enhancer factor 2D isoform X1 [KO:K09262 ]
103669052 CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048 ]
103669178 ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540 ]
103669832 NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332 ]
103669942 GNA12; guanine nucleotide-binding protein subunit alpha-12 [KO:K04346 ]
103672150 MEF2C; myocyte-specific enhancer factor 2C isoform X1 [KO:K04454 ]
103672393 CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048 ]
103673318 PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
103673717 NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333 ]
103673885 CNGB1; LOW QUALITY PROTEIN: cyclic nucleotide-gated cation channel beta-1 [KO:K04952 ]
103674250 SLC8A3; LOW QUALITY PROTEIN: sodium/calcium exchanger 3 [KO:K05849 ]
103674425 PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858 ] [EC:3.1.4.11 ]
103674633 PIK3CG; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform isoform X1 [KO:K21289 ] [EC:2.7.1.153 ]
103674739 CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851 ]
103674803 GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630 ]
103674919 MEF2B; myocyte-specific enhancer factor 2B isoform X1 [KO:K09261 ]
103675000 GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630 ]
103675706 CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850 ]
103676126 KCNMB3; calcium-activated potassium channel subunit beta-3 [KO:K04939 ]
103676128 KCNMB2; calcium-activated potassium channel subunit beta-2 [KO:K04938 ]
103676372 ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374 ]
103677056 VDAC3; voltage-dependent anion-selective channel protein 3 [KO:K15041 ]
103677943 PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
103678432 ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 isoform X1 [KO:K01540 ]
103679332 NFATC4; nuclear factor of activated T-cells, cytoplasmic 4 isoform X1 [KO:K17334 ]
103680852 PPP1R12A; protein phosphatase 1 regulatory subunit 12A isoform X1 [KO:K06270 ]
103681679 CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048 ]
103681813 GNA11; guanine nucleotide-binding protein subunit alpha-11 [KO:K04635 ]
103682282 ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049 ]
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 umr04270 Vascular smooth muscle contraction
KO pathway
