cyclic gmp dependent protein kinases


Summary: A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.

Top Publications

  1. Donald R, Zhong T, Wiersma H, Nare B, Yao D, Lee A, et al. Anticoccidial kinase inhibitors: identification of protein kinase targets secondary to cGMP-dependent protein kinase. Mol Biochem Parasitol. 2006;149:86-98 pubmed
    ..These results provide an example of the utility of the Toxoplasma model system for investigating the mechanism of action of novel anticoccidial agents...
  2. Raizen D, Zimmerman J, Maycock M, Ta U, You Y, Sundaram M, et al. Lethargus is a Caenorhabditis elegans sleep-like state. Nature. 2008;451:569-72 pubmed publisher
    ..The association of this C. elegans sleep-like state with developmental changes that occur with larval moults suggests that sleep may have evolved to allow for developmental changes. ..
  3. Weber S, Bernhard D, Lukowski R, Weinmeister P, Wörner R, Wegener J, et al. Rescue of cGMP kinase I knockout mice by smooth muscle specific expression of either isozyme. Circ Res. 2007;101:1096-103 pubmed
    ..These results show that cGKI in smooth muscle is essential and that either cGKI isozyme alone can rescue basic vascular and intestinal smooth muscle functions. ..
  4. Christensen E, Mendelsohn M. Cyclic GMP-dependent protein kinase Ialpha inhibits thrombin receptor-mediated calcium mobilization in vascular smooth muscle cells. J Biol Chem. 2006;281:8409-16 pubmed
    ..These results support that PKGIalpha is the principal cGMP-dependent protein kinase isoform mediating inhibition of VSMC activation by the nitric oxide/cyclic GMP pathway. ..
  5. Dawson Scully K, Armstrong G, Kent C, Robertson R, Sokolowski M. Natural variation in the thermotolerance of neural function and behavior due to a cGMP-dependent protein kinase. PLoS ONE. 2007;2:e773 pubmed
    ..PKG's role in thermotolerance may also apply to these and other species. Natural variation in thermotolerance arising from genes involved in the PKG pathway could impact the evolution of thermotolerance in natural populations. ..
  6. Scherr N, Honnappa S, Kunz G, Mueller P, Jayachandran R, Winkler F, et al. Structural basis for the specific inhibition of protein kinase G, a virulence factor of Mycobacterium tuberculosis. Proc Natl Acad Sci U S A. 2007;104:12151-6 pubmed
    ..Our results explain the specific mode of action of AX20017 and demonstrate that virulence factors highly homologous to host molecules can be successfully targeted to block the proliferation of M. tuberculosis. ..
  7. Burley D, Ferdinandy P, Baxter G. Cyclic GMP and protein kinase-G in myocardial ischaemia-reperfusion: opportunities and obstacles for survival signaling. Br J Pharmacol. 2007;152:855-69 pubmed
    ..Overall, the body of experimental evidence suggests that cGMP/PKG survival signalling ameliorates irreversible injury associated with ischaemia-reperfusion and may be a tractable therapeutic target. ..
  8. Chan J, Cheng H, Chou J, Li F, Dai K, Chan S, et al. Heat shock protein 60 or 70 activates nitric-oxide synthase (NOS) I- and inhibits NOS II-associated signaling and depresses the mitochondrial apoptotic cascade during brain stem death. J Biol Chem. 2007;282:4585-600 pubmed
    ..In addition, HSP60 exerts its effects against apoptosis by blunting Mev-induced activation of the Bax/cytochrome c/caspase-3 cascade. ..
  9. Wang Q, Pan J, Snell W. Intraflagellar transport particles participate directly in cilium-generated signaling in Chlamydomonas. Cell. 2006;125:549-62 pubmed
    ..Our results lead to a model in which the IFT machinery is required not only for assembling cilia and flagella but also for organizing a signaling pathway within the organelles during cilium-generated signaling. ..

More Information


  1. Niebisch A, Kabus A, Schultz C, Weil B, Bott M. Corynebacterial protein kinase G controls 2-oxoglutarate dehydrogenase activity via the phosphorylation status of the OdhI protein. J Biol Chem. 2006;281:12300-7 pubmed publisher
    ..glutamicum. Moreover, because this signaling cascade is likely to operate also in mycobacteria, our results suggest that the attenuated pathogenicity of mycobacteria lacking PknG might be caused by a disturbed tricarboxylic acid cycle...
  2. Costa A, Garlid K. Intramitochondrial signaling: interactions among mitoKATP, PKCepsilon, ROS, and MPT. Am J Physiol Heart Circ Physiol. 2008;295:H874-82 pubmed publisher
    ..This feedback pathway may be responsible for the lasting protective effect of preconditioning, colloquially known as the memory effect...
  3. Wilson L, Elbatarny H, Crawley S, Bennett B, Maurice D. Compartmentation and compartment-specific regulation of PDE5 by protein kinase G allows selective cGMP-mediated regulation of platelet functions. Proc Natl Acad Sci U S A. 2008;105:13650-5 pubmed publisher
    ..We submit that our findings may define a molecular mechanism by which PDE5 inhibition can differentially impact selected cellular functions of platelets, and perhaps of other cell types. ..
  4. Kaun K, Chakaborty Chatterjee M, Sokolowski M. Natural variation in plasticity of glucose homeostasis and food intake. J Exp Biol. 2008;211:3160-6 pubmed publisher
    ..Finally, rovers have lower adipokinetic hormone (akh) mRNA levels than sitters. Our data suggest that for mediates larval responses to short-term food deprivation by altering food intake and blood glucose levels. ..
  5. Ghosh R, Emmons S. Episodic swimming behavior in the nematode C. elegans. J Exp Biol. 2008;211:3703-11 pubmed publisher
    ..The results show that the motor circuits have a tendency to switch spontaneously between active and inactive behavioral states. This property might be important to the animal in a uniform environment where sensory input is invariant. ..
  6. Takimoto E, Koitabashi N, Hsu S, Ketner E, Zhang M, Nagayama T, et al. Regulator of G protein signaling 2 mediates cardiac compensation to pressure overload and antihypertrophic effects of PDE5 inhibition in mice. J Clin Invest. 2009;119:408-20 pubmed publisher
    ..Thus, RGS2 is required for early myocardial compensation to pressure overload and mediates the initial antihypertrophic and cardioprotective effects of PDE5 inhibitors. ..
  7. Kaye J, Rose N, Goldsworthy B, Goga A, L Etoile N. A 3'UTR pumilio-binding element directs translational activation in olfactory sensory neurons. Neuron. 2009;61:57-70 pubmed publisher
  8. Houben E, Walburger A, Ferrari G, Nguyen L, Thompson C, Miess C, et al. Differential expression of a virulence factor in pathogenic and non-pathogenic mycobacteria. Mol Microbiol. 2009;72:41-52 pubmed publisher
  9. Lucas C, Sokolowski M. Molecular basis for changes in behavioral state in ant social behaviors. Proc Natl Acad Sci U S A. 2009;106:6351-6 pubmed publisher
    ..Finally, pharmacological activation of PKG increases defense and reduces foraging behavior. Thus, PKG signaling plays a critical role in P. pallidula behavioral shifts. ..
  10. Kitazawa T, Semba S, Huh Y, Kitazawa K, Eto M. Nitric oxide-induced biphasic mechanism of vascular relaxation via dephosphorylation of CPI-17 and MYPT1. J Physiol. 2009;587:3587-603 pubmed publisher
    ..Together, these results suggest that NO production suppresses Ca(2+) release, which causes an inactivation of PKC and rapid CPI-17 dephosphorylation as well as MLCK inactivation, resulting in rapid MLC dephosphorylation and relaxation. ..
  11. Kaun K, Riedl C, Chakaborty Chatterjee M, Belay A, Douglas S, Gibbs A, et al. Natural variation in food acquisition mediated via a Drosophila cGMP-dependent protein kinase. J Exp Biol. 2007;210:3547-58 pubmed
    ..Together, these results show that natural variation in for has far reaching implications affecting a suite of phenotypes involved in the regulation of food acquisition. ..
  12. Osei Owusu P, Sun X, Drenan R, Steinberg T, Blumer K. Regulation of RGS2 and second messenger signaling in vascular smooth muscle cells by cGMP-dependent protein kinase. J Biol Chem. 2007;282:31656-65 pubmed
    ..By diminishing cGK activity, endothelial dysfunction may impair RGS2 activation, thereby blunting vascular relaxation and contributing to hypertension. ..
  13. Mery F, Belay A, So A, Sokolowski M, Kawecki T. Natural polymorphism affecting learning and memory in Drosophila. Proc Natl Acad Sci U S A. 2007;104:13051-5 pubmed
  14. Belay A, Scheiner R, So A, Douglas S, Chakaborty Chatterjee M, Levine J, et al. The foraging gene of Drosophila melanogaster: spatial-expression analysis and sucrose responsiveness. J Comp Neurol. 2007;504:570-82 pubmed
    ..We found that pan-neuronal expression of for caused an increase in the SR of sitters, demonstrating a neural function for PKG in this food-related behavior. ..
  15. Kaun K, Hendel T, Gerber B, Sokolowski M. Natural variation in Drosophila larval reward learning and memory due to a cGMP-dependent protein kinase. Learn Mem. 2007;14:342-9 pubmed
    ..The difference in the dynamics of memory acquisition and retention between variants of for suggests that the ability to learn and retain an association may be linked to the foraging strategies of the two variants. ..
  16. Takimoto E, Belardi D, Tocchetti C, Vahebi S, Cormaci G, Ketner E, et al. Compartmentalization of cardiac beta-adrenergic inotropy modulation by phosphodiesterase type 5. Circulation. 2007;115:2159-67 pubmed
    ..Such disparities likely contribute to differential cardiac regulation by drugs that modulate cGMP synthesis and hydrolysis. ..
  17. Chai Y, Lin Y. Dual regulation of the ATP-sensitive potassium channel by activation of cGMP-dependent protein kinase. Pflugers Arch. 2008;456:897-915 pubmed publisher
  18. Costa A, Jakob R, Costa C, Andrukhiv K, West I, Garlid K. The mechanism by which the mitochondrial ATP-sensitive K+ channel opening and H2O2 inhibit the mitochondrial permeability transition. J Biol Chem. 2006;281:20801-8 pubmed
    ..4 (+/-0.1) microm. On the basis of these results, we propose that two different PKCepsilon pools regulate this signaling pathway, one in association with mitoK(ATP) and the other in association with MPT. ..
  19. You Y, Kim J, Raizen D, Avery L. Insulin, cGMP, and TGF-beta signals regulate food intake and quiescence in C. elegans: a model for satiety. Cell Metab. 2008;7:249-57 pubmed publisher
    ..The EGL-4 cGMP-dependent protein kinase functions downstream of insulin and TGF-beta in sensory neurons including ASI to control quiescence in response to food intake. ..
  20. McRobert L, Taylor C, Deng W, Fivelman Q, Cummings R, Polley S, et al. Gametogenesis in malaria parasites is mediated by the cGMP-dependent protein kinase. PLoS Biol. 2008;6:e139 pubmed publisher
    ..falciparum, and demonstrates the feasibility of selective inhibition of a crucial regulator of the malaria parasite life cycle. ..
  21. Takahashi S, Lin H, Geshi N, Mori Y, Kawarabayashi Y, Takami N, et al. Nitric oxide-cGMP-protein kinase G pathway negatively regulates vascular transient receptor potential channel TRPC6. J Physiol. 2008;586:4209-23 pubmed publisher
    ..This mechanism may be physiologically important in vascular tissues where NO is constantly released from vascular endothelial cells or nitrergic nerves. ..
  22. van der Linden A, Wiener S, You Y, Kim K, Avery L, Sengupta P. The EGL-4 PKG acts with KIN-29 salt-inducible kinase and protein kinase A to regulate chemoreceptor gene expression and sensory behaviors in Caenorhabditis elegans. Genetics. 2008;180:1475-91 pubmed publisher
    ..Our results suggest that integration of complex sensory inputs via multiple signaling pathways allows animals to precisely regulate sensory gene expression, thereby appropriately modulating physiology and behavior. ..
  23. O Hare H, Duran R, Cerveñansky C, Bellinzoni M, Wehenkel A, Pritsch O, et al. Regulation of glutamate metabolism by protein kinases in mycobacteria. Mol Microbiol. 2008;70:1408-23 pubmed publisher
    ..Previous reports of a defect in glutamate metabolism caused by pknG deletion may thus be explained by the effect of unphosphorylated GarA on these two enzyme activities, which may also contribute to the attenuation of virulence. ..
  24. Chan J, Wu C, Tsai C, Cheng H, Dai K, Chan S, et al. Transcriptional up-regulation of nitric oxide synthase II by nuclear factor-kappaB at rostral ventrolateral medulla in a rat mevinphos intoxication model of brain stem death. J Physiol. 2007;581:1293-307 pubmed
  25. Raizen D, Cullison K, Pack A, Sundaram M. A novel gain-of-function mutant of the cyclic GMP-dependent protein kinase egl-4 affects multiple physiological processes in Caenorhabditis elegans. Genetics. 2006;173:177-87 pubmed
    ..In a genetic screen we have identified extragenic suppressors of this gain-of-function mutant. Thus, this mutant promises to be a useful tool for identifying downstream targets of PKG. ..
  26. Schmidtko A, Gao W, Konig P, Heine S, Motterlini R, Ruth P, et al. cGMP produced by NO-sensitive guanylyl cyclase essentially contributes to inflammatory and neuropathic pain by using targets different from cGMP-dependent protein kinase I. J Neurosci. 2008;28:8568-76 pubmed publisher
    ..Together, our results provide evidence that NO-GC is crucially involved in the central sensitization of pain pathways during inflammatory and neuropathic pain. ..
  27. Ota K, Pierre V, Ploski J, Queen K, Schafe G. The NO-cGMP-PKG signaling pathway regulates synaptic plasticity and fear memory consolidation in the lateral amygdala via activation of ERK/MAP kinase. Learn Mem. 2008;15:792-805 pubmed publisher
  28. Douglas S, Dawson Scully K, Sokolowski M. The neurogenetics and evolution of food-related behaviour. Trends Neurosci. 2005;28:644-52 pubmed
    ..We focus on synthesizing neurobiological and genetic approaches into a neurogenetic framework that explains food-related behaviour as the product of interactions between neural substrates, genes and internal and external environments. ..
  29. He B, Weber G. Synergistic activation of the CMV promoter by NF-kappaB P50 and PKG. Biochem Biophys Res Commun. 2004;321:13-20 pubmed
    ..These interactions may be relevant for the activation of viral gene expression. ..
  30. Tischkau S, Mitchell J, Pace L, Barnes J, Barnes J, Gillette M. Protein kinase G type II is required for night-to-day progression of the mammalian circadian clock. Neuron. 2004;43:539-49 pubmed
    ..PKG-II activation may define a critical control point for temporal progression into the daytime domain by acting on the positive arm of the transcriptional/translational feedback loop. ..
  31. Chikuda H, Kugimiya F, Hoshi K, Ikeda T, Ogasawara T, Shimoaka T, et al. Cyclic GMP-dependent protein kinase II is a molecular switch from proliferation to hypertrophic differentiation of chondrocytes. Genes Dev. 2004;18:2418-29 pubmed
  32. Krejci P, Masri B, Fontaine V, Mekikian P, Weis M, Prats H, et al. Interaction of fibroblast growth factor and C-natriuretic peptide signaling in regulation of chondrocyte proliferation and extracellular matrix homeostasis. J Cell Sci. 2005;118:5089-100 pubmed
    ..We conclude that CNP utilizes both direct and indirect ways to counteract the effects of FGF signaling in a chondrocyte environment. ..
  33. Schlossmann J, Hofmann F. cGMP-dependent protein kinases in drug discovery. Drug Discov Today. 2005;10:627-34 pubmed
    ..Isozyme-specific inhibitors and activators of cGK and its downstream substrates might act more specifically than upstream signalling activators, such as organic nitrates and phosphodiesterase inhibitors. ..
  34. Feil R, Hofmann F, Kleppisch T. Function of cGMP-dependent protein kinases in the nervous system. Rev Neurosci. 2005;16:23-41 pubmed
    ..Thus, cGKs serve key functions in the transduction of cGMP signals into cellular responses in distinct regions of the nervous system.- ..
  35. Pilz R, Broderick K. Role of cyclic GMP in gene regulation. Front Biosci. 2005;10:1239-68 pubmed
    ..We will discuss specific genes regulated by cGMP in the context of their contribution to particular (patho)physiologic processes regulated by cGMP. ..
  36. Wang H, Lu F, Jin I, Udo H, Kandel E, de Vente J, et al. Presynaptic and postsynaptic roles of NO, cGK, and RhoA in long-lasting potentiation and aggregation of synaptic proteins. Neuron. 2005;45:389-403 pubmed
    ..cGK phosphorylates synaptic VASP during the potentiation, whereas Rho GTPases act both in parallel and upstream of cGMP, in part by maintaining the synaptic localization of soluble guanylyl cyclase. ..
  37. Hofmann F. The biology of cyclic GMP-dependent protein kinases. J Biol Chem. 2005;280:1-4 pubmed
  38. Diaz C, Allocco J, Powles M, Yeung L, Donald R, Anderson J, et al. Characterization of Plasmodium falciparum cGMP-dependent protein kinase (PfPKG): antiparasitic activity of a PKG inhibitor. Mol Biochem Parasitol. 2006;146:78-88 pubmed
    ..Compound 1 is active against blood cell stages of P. falciparum cultured in vitro. In a Plasmodium berghei mouse model of infection, Compound 1 delays the onset of parasitemia but does not cure the parasite infection. ..
  39. Chan J, Chan S, Li F, Tsai C, Cheng H, Chang A. Phasic cardiovascular responses to mevinphos are mediated through differential activation of cGMP/PKG cascade and peroxynitrite via nitric oxide generated in the rat rostral ventrolateral medulla by NOS I and II isoforms. Neuropharmacology. 2005;48:161-72 pubmed
    ..We conclude that sGC/cGMP/PKG cascade and peroxynitrite formation may participate in Mev-induced phasic cardiovascular responses as signals downstream to NO generated respectively by NOS I and II in the RVLM. ..
  40. Alonso Magdalena P, Laribi O, Ropero A, Fuentes E, Ripoll C, Soria B, et al. Low doses of bisphenol A and diethylstilbestrol impair Ca2+ signals in pancreatic alpha-cells through a nonclassical membrane estrogen receptor within intact islets of Langerhans. Environ Health Perspect. 2005;113:969-77 pubmed
    ..The action of E2, BPA, and DES in pancreatic alpha-cells may explain some of the effects elicited by endocrine disruptors in the metabolism of glucose and lipid. ..
  41. Ingram K, Oefner P, Gordon D. Task-specific expression of the foraging gene in harvester ants. Mol Ecol. 2005;14:813-8 pubmed publisher
    ..The association between foraging behaviour and the foraging gene is conserved across social insects but ants and bees have an inverse relationship between foraging expression and behaviour...
  42. Feil S, Zimmermann P, Knorn A, Brummer S, Schlossmann J, Hofmann F, et al. Distribution of cGMP-dependent protein kinase type I and its isoforms in the mouse brain and retina. Neuroscience. 2005;135:863-8 pubmed
  43. Nguyen L, Walburger A, Houben E, Koul A, Muller S, Morbitzer M, et al. Role of protein kinase G in growth and glutamine metabolism of Mycobacterium bovis BCG. J Bacteriol. 2005;187:5852-6 pubmed
    ..In vitro growth of Mycobacterium bovis BCG lacking pknG was identical to that of the wild type. We conclude that in M. bovis BCG, glutamine metabolism is not regulated by protein kinase G. ..
  44. Costa A, Garlid K, West I, Lincoln T, Downey J, Cohen M, et al. Protein kinase G transmits the cardioprotective signal from cytosol to mitochondria. Circ Res. 2005;97:329-36 pubmed
    ..We conclude PKG is the terminal cytosolic component of the trigger pathway; it transmits the cardioprotective signal from cytosol to inner mitochondrial membrane by a pathway that includes PKC-epsilon. ..
  45. Giricz Z, Gorbe A, Pipis J, Burley D, Ferdinandy P, Baxter G. Hyperlipidaemia induced by a high-cholesterol diet leads to the deterioration of guanosine-3',5'-cyclic monophosphate/protein kinase G-dependent cardioprotection in rats. Br J Pharmacol. 2009;158:1495-502 pubmed publisher
    ..This is the first demonstration that defects in the cardioprotective cGMP-PKG system could be a critical biochemical anomaly in hyperlipidaemia. ..
  46. Garabagi F, Wade French B, Schaafsma A, Peter Pauls K. Increased expression of a cGMP-dependent protein kinase in rotation-adapted western corn rootworm (Diabrotica virgifera virgifera L.). Insect Biochem Mol Biol. 2008;38:697-704 pubmed publisher
    ..However, Diabrotica contains at least two different foraging gene transcripts, which complicates establishing a direct link between the level of gene expression and insect behavior. ..
  47. Wang T, Li K, Wei L. [Roles of vasodilator-stimulated phosphoprotein in the regulation of cytoskeleton]. Sheng Li Ke Xue Jin Zhan. 2006;37:27-30 pubmed
  48. Chamorro Jorganes A, Grande M, Herranz B, Jerkic M, Griera M, Gonzalez Nuñez M, et al. Targeted genomic disruption of h-ras induces hypotension through a NO-cGMP-PKG pathway-dependent mechanism. Hypertension. 2010;56:484-9 pubmed publisher
    ..Moreover, they suggest that H-Ras pathway could be considered as a therapeutic target for hypertension treatment. ..
  49. Zhang Y, Gesmonde J, Ramamoorthy S, Rudnick G. Serotonin transporter phosphorylation by cGMP-dependent protein kinase is altered by a mutation associated with obsessive compulsive disorder. J Neurosci. 2007;27:10878-86 pubmed
    ..However, association of hSERT with protein phosphatase 2A was not decreased in the I425V mutant. ..
  50. Haider H, Lee Y, Jiang S, Ahmed R, Ryon M, Ashraf M. Phosphodiesterase inhibition with tadalafil provides longer and sustained protection of stem cells. Am J Physiol Heart Circ Physiol. 2010;299:H1395-404 pubmed publisher
    ..PDE5A inhibition using long-acting tadalafil is an innovative approach to promote stem cell survival and proliferation in the infarcted heart. ..
  51. Xi J, Tian W, Zhang L, Jin Y, Xu Z. Morphine prevents the mitochondrial permeability transition pore opening through NO/cGMP/PKG/Zn2+/GSK-3beta signal pathway in cardiomyocytes. Am J Physiol Heart Circ Physiol. 2010;298:H601-7 pubmed publisher
    ..In conclusion, morphine mobilizes intracellular Zn(2+) through the NO/cGMP/PKG signaling pathway and prevents the mPTP opening by inactivating GSK-3beta through Zn(2+). ..
  52. Burnette J, White R. PGI2 opens potassium channels in retinal pericytes by cyclic AMP-stimulated, cross-activation of PKG. Exp Eye Res. 2006;83:1359-65 pubmed
    ..Further, we propose PKG-dependent stimulation of BKCa channel activity as a new potential therapeutic target to combat decreased retinal blood flow seen in some disease states (e.g., diabetic retinopathy). ..
  53. Azadzoi K. Editorial comment on: Immunohistochemical distribution of cyclic GMP-dependent protein kinase-1 in human prostate tissue. Eur Urol. 2007;52:501-2 pubmed