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Adk  -  adenosine kinase

Rattus norvegicus

Synonyms: AK, Adenosine 5'-phosphotransferase, Adenosine kinase
 
 
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Disease relevance of Adk

 

Psychiatry related information on Adk

 

High impact information on Adk

  • The A-kinase-anchoring proteins (AKAPs; ref. 3) are known to bind the regulatory subunit of cyclic AMP-dependent protein kinase A with nanomolar affinity [10].
  • These results indicate that the catalytic subunit of A kinase is sufficient to induce expression of two cAMP-responsive genes, without increasing levels of cAMP [11].
  • The regulatory subunits of the A kinase, which bind cAMP and DNA, and have amino-acid homology with the Escherichia coli catabolite activator protein could directly stimulate gene expression [11].
  • To distinguish between these models, we microinjected purified preparations of the catalytic and regulatory subunits of A kinase into tissue culture cells and monitored expression of a stably integrated fusion gene containing a cAMP-responsive human promoter fused to a bacterial reporter gene, or of the endogenous c-fos gene [11].
  • Neuroscience. A kinase to dampen the effects of cociane [12]?
 

Chemical compound and disease context of Adk

 

Biological context of Adk

  • We concluded that insulin stimulates AK gene expression through a series of events occurring sequentially [17].
  • Transfection of an adenosine-kinase-deficient mutant (selected for resistance to the adenosine analog toyocamycin) of Chinese hamster ovary cells with a plasmid containing the cloned adenosine kinase cDNA, leads to regaining of adenosine kinase activity in the transformed cell [18].
  • In addition, we describe a novel protein kinase A (PKA)-dependent signaling module, containing PKA and a putative A kinase adapter protein, Acyl CoA binding domain protein (ACBD)3, that interacts with TRPV2 in mast cells [19].
  • Expression of the type II/IIA sodium channel requires activation of the cyclic AMP-dependent protein kinase (A-kinase), whereas induction of the peripheral neuron type sodium channel occurs through an A-kinase-independent signal transduction pathway [20].
  • Microinjection of the catalytic subunit of cAMP-dependent protein kinase (A-kinase) into living fibroblasts or the treatment of these cells with agents that elevate the intracellular cAMP level caused marked alterations in cell morphology including a rounded phenotype and a complete loss of actin microfilament bundles [21].
 

Anatomical context of Adk

  • Experiments performed on cultured rat lymphocytes demonstrated that insulin did not change the stability of AK mRNA [17].
  • In addition, the coding and upstream sequences for adenosine kinase from human (HeLa cells) and rat liver have also been cloned and sequenced [18].
  • Using microsequence information from peptides derived from purified Syrian hamster liver enzyme, we have succeeded in isolating full length cDNA clones encoding adenosine kinase from Chinese hamster ovary cells and mouse 3T3 cells [18].
  • Measurement of AK activity in cytosolic fractions of rat tissues showed the highest activity in the liver (0.58 U/g), which decreased in the order kidney > spleen > lung > brain > heart > skeletal muscle [22].
  • Adk-deficient stem cells therefore represent a potential tool for the treatment of epileptic disorders [3].
 

Associations of Adk with chemical compounds

  • The insulin effect on AK expression was not influenced by dibutyryl cAMP (dcAMP) [17].
  • In view of its central role in adenosine metabolism, which is an important physiological regulator, an understanding of the primary structure of adenosine kinase is of much interest [18].
  • The enzyme adenosine kinase constitutes the major purine nucleoside phosphorylating activity in mammalian cells [18].
  • The adenosine kinase transformants also simultaneously lost their toyocamycin resistance and became similarly sensitive to the analog as the parental wild-type Chinese hamster ovary cells [18].
  • Pretreatment with the adenosine kinase inhibitor, 5-iodotubercidin (1 mg/kg), limited infarct development to 37.5+/-3.7% (P < 0.001) [2].
 

Regulatory relationships of Adk

 

Other interactions of Adk

 

Analytical, diagnostic and therapeutic context of Adk

  • Results of Southern and northern-blot analysis provide evidence that this group of mutants involves gross structural alterations affecting the adenosine kinase gene [18].
  • Moreover, inhibiting MLCK activity via microinjection of affinity-purified antibodies specific to native MLCK caused a complete loss of microfilament bundle integrity and a decrease in myosin P-light chain phosphorylation, similar to that seen after injection of A-kinase [21].
  • Analysis of the sites of phosphorylation on vimentin from injected cells by either V8 protease cleavage, or two-dimensional tryptic peptide mapping, revealed increased de novo phosphorylation of two vimentin phosphopeptides after microinjection of A-kinase [26].
  • Two-dimensional gel electrophoresis was used to analyze the changes in phosphoproteins from cells injected with A-kinase [21].
  • With the use of -cAMP/+cAMP activity ratios of cAMP-dependent protein kinase (A-kinase) in fat cell extracts as an index of cellular cAMP concentrations, it is apparent from both the current literature and from data presented in this paper that classical cell isolation procedures yield cells whose behavior is unpredictable from day to day [27].

References

  1. Cloning and expression of the adenosine kinase gene from rat and human tissues. McNally, T., Helfrich, R.J., Cowart, M., Dorwin, S.A., Meuth, J.L., Idler, K.B., Klute, K.A., Simmer, R.L., Kowaluk, E.A., Halbert, D.N. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  2. Cardioprotection following adenosine kinase inhibition in rat hearts. Peart, J.N., Gross, G.J. Basic Res. Cardiol. (2005) [Pubmed]
  3. Suppression of kindled seizures by paracrine adenosine release from stem cell-derived brain implants. Güttinger, M., Fedele, D., Koch, P., Padrun, V., Pralong, W.F., Brüstle, O., Boison, D. Epilepsia (2005) [Pubmed]
  4. Rat hepatomas: chemotherapy with lycurim and pyrazofurin. Lui, M.S., Jackson, R.C., Harkrader, R.J., Weber, G. J. Natl. Cancer Inst. (1982) [Pubmed]
  5. Anti-inflammatory effects of an adenosine kinase inhibitor. Decreased neutrophil accumulation and vascular leakage. Rosengren, S., Bong, G.W., Firestein, G.S. J. Immunol. (1995) [Pubmed]
  6. Adenosine kinase inhibitors. 2. Synthesis, enzyme inhibition, and antiseizure activity of diaryltubercidin analogues. Ugarkar, B.G., Castellino, A.J., DaRe, J.M., Kopcho, J.J., Wiesner, J.B., Schanzer, J.M., Erion, M.D. J. Med. Chem. (2000) [Pubmed]
  7. Enzymes of adenosine metabolism in the brain: diurnal rhythm and the effect of sleep deprivation. Mackiewicz, M., Nikonova, E.V., Zimmerman, J.E., Galante, R.J., Zhang, L., Cater, J.R., Geiger, J.D., Pack, A.I. J. Neurochem. (2003) [Pubmed]
  8. Effects of A-134974, a novel adenosine kinase inhibitor, on carrageenan-induced inflammatory hyperalgesia and locomotor activity in rats: evaluation of the sites of action. McGaraughty, S., Chu, K.L., Wismer, C.T., Mikusa, J., Zhu, C.Z., Cowart, M., Kowaluk, E.A., Jarvis, M.F. J. Pharmacol. Exp. Ther. (2001) [Pubmed]
  9. Adenosine kinase and 5'-nucleotidase activity after prolonged wakefulness in the cortex and the basal forebrain of rat. Alanko, L., Heiskanen, S., Stenberg, D., Porkka-Heiskanen, T. Neurochem. Int. (2003) [Pubmed]
  10. Anchoring of protein kinase A is required for modulation of AMPA/kainate receptors on hippocampal neurons. Rosenmund, C., Carr, D.W., Bergeson, S.E., Nilaver, G., Scott, J.D., Westbrook, G.L. Nature (1994) [Pubmed]
  11. The catalytic subunit of cAMP-dependent protein kinase induces expression of genes containing cAMP-responsive enhancer elements. Riabowol, K.T., Fink, J.S., Gilman, M.Z., Walsh, D.A., Goodman, R.H., Feramisco, J.R. Nature (1988) [Pubmed]
  12. Neuroscience. A kinase to dampen the effects of cociane? Gupta, A., Tsai, L.H. Science (2001) [Pubmed]
  13. Protective effect of an adenosine kinase inhibitor in septic shock. Firestein, G.S., Boyle, D., Bullough, D.A., Gruber, H.E., Sajjadi, F.G., Montag, A., Sambol, B., Mullane, K.M. J. Immunol. (1994) [Pubmed]
  14. Cloning and characterization of an adenosine kinase from Physcomitrella involved in cytokinin metabolism. von Schwartzenberg, K., Kruse, S., Reski, R., Moffatt, B., Laloue, M. Plant J. (1998) [Pubmed]
  15. Mechanisms of elevation of adenosine levels in anoxic hepatocytes. Bontemps, F., Vincent, M.F., Van den Berghe, G. Biochem. J. (1993) [Pubmed]
  16. Phosphorylation of adenosine in anoxic hepatocytes by an exchange reaction catalysed by adenosine kinase. Bontemps, F., Mimouni, M., Van den Berghe, G. Biochem. J. (1993) [Pubmed]
  17. Insulin induces expression of adenosine kinase gene in rat lymphocytes by signaling through the mitogen-activated protein kinase pathway. Pawelczyk, T., Sakowicz, M., Podgorska, M., Szczepanska-Konkel, M. Exp. Cell Res. (2003) [Pubmed]
  18. Cloning and characterization of cDNA for adenosine kinase from mammalian (Chinese hamster, mouse, human and rat) species. High frequency mutants of Chinese hamster ovary cells involve structural alterations in the gene. Singh, B., Hao, W., Wu, Z., Eigl, B., Gupta, R.S. Eur. J. Biochem. (1996) [Pubmed]
  19. A TRPV2-PKA signaling module for transduction of physical stimuli in mast cells. Stokes, A.J., Shimoda, L.M., Koblan-Huberson, M., Adra, C.N., Turner, H. J. Exp. Med. (2004) [Pubmed]
  20. Neuronal growth factor regulation of two different sodium channel types through distinct signal transduction pathways. D'Arcangelo, G., Paradiso, K., Shepherd, D., Brehm, P., Halegoua, S., Mandel, G. J. Cell Biol. (1993) [Pubmed]
  21. Regulation of actin microfilament integrity in living nonmuscle cells by the cAMP-dependent protein kinase and the myosin light chain kinase. Lamb, N.J., Fernandez, A., Conti, M.A., Adelstein, R., Glass, D.B., Welch, W.J., Feramisco, J.R. J. Cell Biol. (1988) [Pubmed]
  22. Expression level of adenosine kinase in rat tissues. Lack of phosphate effect on the enzyme activity. Sakowicz, M., Grdeń, M., Pawełczyk, T. Acta Biochim. Pol. (2001) [Pubmed]
  23. Dysregulation of extracellular adenosine levels by vascular smooth muscle cells from spontaneously hypertensive rats. Dubey, R., Mi, Z., Gillespie, D.G., Jackson, E.K. Arterioscler. Thromb. Vasc. Biol. (2001) [Pubmed]
  24. Increases in interstitial adenosine and cerebral blood flow with inhibition of adenosine kinase and adenosine deaminase. Sciotti, V.M., Van Wylen, D.G. J. Cereb. Blood Flow Metab. (1993) [Pubmed]
  25. Restoring adenine nucleotides in a brain slice model of cerebral reperfusion. Newman, G.C., Hospod, F.E., Trowbridge, S.D., Motwani, S., Liu, Y. J. Cereb. Blood Flow Metab. (1998) [Pubmed]
  26. Modulation of vimentin containing intermediate filament distribution and phosphorylation in living fibroblasts by the cAMP-dependent protein kinase. Lamb, N.J., Fernandez, A., Feramisco, J.R., Welch, W.J. J. Cell Biol. (1989) [Pubmed]
  27. cAMP-dependent protein kinase and lipolysis in rat adipocytes. I. Cell preparation, manipulation, and predictability in behavior. Honnor, R.C., Dhillon, G.S., Londos, C. J. Biol. Chem. (1985) [Pubmed]
 
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