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Gene Review

Pkg21D  -  cGMP-dependent protein kinase 21D

Drosophila melanogaster

Synonyms: CG3324, DG1, Dg1, Dmel\CG3324, PKG, ...
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Disease relevance of Pkg21D

  • Perturbing components of the NO/cGMP pathway altered both tracheal development and survival during prolonged hypoxia [1].
  • This manifests itself as hypersensitivity of epithelial fluid transport to the nitridergic neuropeptide, capa-1, which acts through nitric oxide and cGMP [2].
  • There was no evidence that the cAMP system is part of the modulatory mechanism. cGMP is likely to be integral to one active pathway, as non-hydrolyzable forms of this cyclic nucleotide increase heart rate, and flies bearing the mutation sitter, a recessive allele of the foraging gene, which encodes a cGMP-dependent kinase, have tachycardia [3].

High impact information on Pkg21D

  • Nitric oxide activates soluble guanylate cyclase in target cells, leading to the formation of cGMP [4].
  • These results suggest NO and cGMP act to stabilize retinal growth cones at the start of synaptic assembly [5].
  • This antidiuretic factor (ADF) appears to elicit its effect via cGMP as a second messenger but does not stimulate NO production [6].
  • The cDNA for a membrane-associated cGMP-dependent protein kinase (cGK II) was cloned from rat intestine using reverse transcriptase PCR and oligonucleotide primers encoding two conserved motifs of known cGMP-dependent protein kinases and subsequently by screening a rat intestine cDNA library [7].
  • Activation is specific and it cannot be mimicked by a series of agents that include AMP, cGMP, ATP, inositol trisphosphate, and Ca2+ [8].

Biological context of Pkg21D

  • The deduced product of one gene (DG1; cytological position, 21D) is 14% larger than the bovine enzyme and differs substantially in sequence at the amino terminus, the region responsible in the bovine enzyme for dimerization [9].
  • A common progenitor of the two cGMP-dependent protein kinase genes, DG1 and DG2, is strongly suggested by the conserved positions of introns in these genes [9].
  • The catalytic subunit gene and the cGMP-dependent protein kinase gene have been located in regions 30C and 21D, respectively, of chromosome 2 [10].
  • DNA sequence analysis demonstrates that this fragment is part of the cGMP-dependent protein kinase gene or a close homolog [10].
  • Tissue distribution of the DG1 kinase was investigated by immunohistochemistry [11].

Anatomical context of Pkg21D


Associations of Pkg21D with chemical compounds

  • The concentrations of cGMP, cAMP, cIMP, 8-bromo-cGMP, and 8-bromo-cAMP that gave 50% activation were 0.19 +/- 0.06, 11.7 +/- 2.8, 5.3 +/- 1.5, 0.04 +/- 0 [11].
  • Evidence is mounting that phototransduction in Drosophila and other invertebrate species may additionally involve the second messenger, cyclic-GMP (cGMP) [16].
  • The functions of intracellular second messengers, such as guanosine 3'5'-cyclic monophosphate (cGMP), adenosine 3'5'-cyclic monophosphate (cAMP), and intracellular calcium, are thus intensively studied [17].
  • Compound 1 is a potent inhibitor of both soluble and membrane-associated isoforms of native PKG, as well as recombinant enzyme, with an IC(50) of <1 nm [18].
  • Furthermore, inhibition of PDE5 activity by sildenafil restores basal and cGMP-stimulated fluid transport rates to control levels [19].

Regulatory relationships of Pkg21D


Other interactions of Pkg21D

  • The largest (DG2; T1) and smallest (DG2;T3) RNAs encode overlapping polypeptides of similar sequence to the whole length of bovine lung cGMP-dependent protein kinase [9].
  • Two Drosophila genes encoding products related to cGMP-dependent protein kinase have been isolated by cross-hybridization to a Drosophila cAMP-dependent protein kinase catalytic subunit gene [9].
  • 01, and 0.62 +/- 0.06 microM, respectively. cGMP activation was cooperative with a Hill coefficient (nH) of 1.28 +/- 0.10, whereas activation by cAMP was not cooperative [11].
  • Furthermore, a novel epithelial role is suggested for DG1, which is considerably more responsive to cGMP than to capa-1 stimulation [12].

Analytical, diagnostic and therapeutic context of Pkg21D

  • Furthermore, cGMP induces a slow [Ca2+]i increase in tubule principal cells via verapamil- and nifedipine-sensitive calcium entry; RT-PCR shows that tubules express Drosophila cyclic nucleotide-gated channel (cng) [21].


  1. Nitric oxide contributes to behavioral, cellular, and developmental responses to low oxygen in Drosophila. Wingrove, J.A., O'Farrell, P.H. Cell (1999) [Pubmed]
  2. The dg2 (for) gene confers a renal phenotype in Drosophila by modulation of cGMP-specific phosphodiesterase. MacPherson, M.R., Broderick, K.E., Graham, S., Day, J.P., Houslay, M.D., Dow, J.A., Davies, S.A. J. Exp. Biol. (2004) [Pubmed]
  3. Modulation of the cardiac pacemaker of Drosophila: cellular mechanisms. Johnson, E., Sherry, T., Ringo, J., Dowse, H. J. Comp. Physiol. B, Biochem. Syst. Environ. Physiol. (2002) [Pubmed]
  4. NO news from insect brains. Bicker, G. Trends Neurosci. (1998) [Pubmed]
  5. Nitric oxide and cyclic GMP regulate retinal patterning in the optic lobe of Drosophila. Gibbs, S.M., Truman, J.W. Neuron (1998) [Pubmed]
  6. Identification of a potent antidiuretic factor acting on beetle Malpighian tubules. Eigenheer, R.A., Nicolson, S.W., Schegg, K.M., Hull, J.J., Schooley, D.A. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  7. Cloning, expression, and in situ localization of rat intestinal cGMP-dependent protein kinase II. Jarchau, T., Häusler, C., Markert, T., Pöhler, D., Vanderkerckhove, J., De Jonge, H.R., Lohmann, S.M., Walter, U. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  8. A cyclic AMP-activated K+ channel in Drosophila larval muscle is persistently activated in dunce. Delgado, R., Hidalgo, P., Diaz, F., Latorre, R., Labarca, P. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  9. cGMP-dependent protein kinase genes in Drosophila. Kalderon, D., Rubin, G.M. J. Biol. Chem. (1989) [Pubmed]
  10. Cloning, sequence, and expression of the Drosophila cAMP-dependent protein kinase catalytic subunit gene. Foster, J.L., Higgins, G.C., Jackson, F.R. J. Biol. Chem. (1988) [Pubmed]
  11. Biochemical properties and cellular localization of the Drosophila DG1 cGMP-dependent protein kinase. Foster, J.L., Higgins, G.C., Jackson, F.R. J. Biol. Chem. (1996) [Pubmed]
  12. Analysis of Drosophila cGMP-dependent protein kinases and assessment of their in vivo roles by targeted expression in a renal transporting epithelium. MacPherson, M.R., Lohmann, S.M., Davies, S.A. J. Biol. Chem. (2004) [Pubmed]
  13. Characterization of the human gene encoding the type I alpha and type I beta cGMP-dependent protein kinase (PRKG1). Orstavik, S., Natarajan, V., Taskén, K., Jahnsen, T., Sandberg, M. Genomics (1997) [Pubmed]
  14. Coupling of photoexcited rhodopsin to inositol phospholipid hydrolysis in fly photoreceptors. Devary, O., Heichal, O., Blumenfeld, A., Cassel, D., Suss, E., Barash, S., Rubinstein, C.T., Minke, B., Selinger, Z. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  15. Nitric oxide and cyclic GMP induce vesicle release at Drosophila neuromuscular junction. Wildemann, B., Bicker, G. J. Neurobiol. (1999) [Pubmed]
  16. Cyclic-GMP enhances light-induced excitation and induces membrane currents in Drosophila retinal photoreceptors. Bacigalupo, J., Bautista, D.M., Brink, D.L., Hetzer, J.F., O'Day, P.M. J. Neurosci. (1995) [Pubmed]
  17. Cell-specific manipulation of second messengers; a toolbox for integrative physiology in Drosophila. Kerr, M., Davies, S.A., Dow, J.A. Curr. Biol. (2004) [Pubmed]
  18. Purification and molecular characterization of cGMP-dependent protein kinase from Apicomplexan parasites. A novel chemotherapeutic target. Gurnett, A.M., Liberator, P.A., Dulski, P.M., Salowe, S.P., Donald, R.G., Anderson, J.W., Wiltsie, J., Diaz, C.A., Harris, G., Chang, B., Darkin-Rattray, S.J., Nare, B., Crumley, T., Blum, P.S., Misura, A.S., Tamas, T., Sardana, M.K., Yuan, J., Biftu, T., Schmatz, D.M. J. Biol. Chem. (2002) [Pubmed]
  19. Ectopic expression of bovine type 5 phosphodiesterase confers a renal phenotype in Drosophila. Broderick, K.E., Kean, L., Dow, J.A., Pyne, N.J., Davies, S.A. J. Biol. Chem. (2004) [Pubmed]
  20. The regulatory subunit of a cGMP-regulated protein kinase A of Trypanosoma brucei. Shalaby, T., Liniger, M., Seebeck, T. Eur. J. Biochem. (2001) [Pubmed]
  21. Model organisms: new insights into ion channel and transporter function. L-type calcium channels regulate epithelial fluid transport in Drosophila melanogaster. MacPherson, M.R., Pollock, V.P., Broderick, K.E., Kean, L., O'Connell, F.C., Dow, J.A., Davies, S.A. Am. J. Physiol., Cell Physiol. (2001) [Pubmed]
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